Unexpected Role of MPO-Oxidized LDLs in Atherosclerosis: Comparison
View Latest Version
Please note this is a comparison between Version 2 by Lindsay Dong and Version 1 by Cecilia Tangeten.

Inflammation and its resolution are the result of the balance between pro-inflammatory and pro-resolving factors, such as specialized pro-resolving mediators (SPMs). This balance is crucial for plaque evolution in atherosclerosis, a chronic inflammatory disease. Myeloperoxidase (MPO) has been related to oxidative stress and atherosclerosis, and MPO-oxidized low-density lipoproteins (Mox-LDLs) have specific characteristics and effects. They participate in foam cell formation and cause specific reactions when interacting with macrophages and endothelial cells. They also increase the production of intracellular reactive oxygen species (ROS) in macrophages and the resulting antioxidant response. Mox-LDLs also drive macrophage polarization. Mox-LDLs are known to be pro-inflammatory particles. However, in the presence of Mox-LDLs, endothelial cells produce resolvin D1 (RvD1), a SPM. SPMs are involved in the resolution of inflammation by stimulating efferocytosis and by reducing the adhesion and recruitment of neutrophils and monocytes. RvD1 also induces the synthesis of other SPMs. In vitro, Mox-LDLs have a dual effect by promoting RvD1 release and inducing a more anti-inflammatory phenotype macrophage, thereby having a mixed effect on inflammation.

  • myeloperoxidase
  • atherosclerosis
  • inflammation
  • myeloperoxidase oxidized low-density lipoprotein
  • specialized pro-resolving mediators
  • resolvin D1

1. Introduction

Atherosclerosis is a vascular disease characterized by chronic inflammation and the formation of atheromatous plaques in large and medium-sized arteries. Destabilization of plaques can lead to life-threatening events such as stroke and heart attack, so it is critical that the mechanisms involved in plaque development and rupture are well understood[1]. The clinical consequences of atherosclerosis are most likely determined by the inflammatory environment, which is the result of a balance between the pro-inflammatory and pro-resolving factors[2]. Vulnerable human atherosclerotic plaques have a lower pro-resolving/pro-inflammatory ratio than stable plaques, and the restoration of this balance promotes plaque stability in mice[3]. Therefore, the progression of atherosclerosis may be linked to a defective inflammation–resolution process. The lipid mediators involved in inflammation resolution are called specialized pro-resolving mediators (SPMs)[4]. The production of SPMs enables the body to compensate for the deleterious effects of inflammation. SPMs are rapidly produced at the onset of inflammation and co-exist with pro-inflammatory signals. The balance between these pro-inflammatory signals and SPMs determines the duration and intensity of inflammation[5].
MPO is considered a biomarker for various chronic inflammatory diseases, including cardiovascular disease and rheumatoid arthritis. In addition, plasma MPO levels may be related to increased risk, severity, and extent of coronary artery diseases (CAD) in patients[6][7]. Elevated plasma MPO concentrations have been reported in patients with CAD, unstable angina, and acute myocardial infarction[6][8]. The involvement of MPO in cardiovascular diseases is often related to its pro-oxidant activity. MPO is one of the main physiological ways by which low-density (LDL) and high-density (HDL) lipoproteins can be oxidized[9][10]. Oxidized LDLs and HDLs are involved in the development and progression of atheromatous plaques and inflammation[11]. MPO oxidized-LDLs (Mox-LDLs) have multiple effects on cells involved in the development of atherosclerosis. They induce the production of pro-inflammatory mediators, interleukin-8 (IL-8) and tumor-necrosis factor-α (TNF-α), by endothelial cells and macrophages respectively[12].

2. Myeloperoxidase

MPO is a heme-containing enzyme that was first known for its role in the body’s defense against pathogens. This enzyme is mainly found in azurophilic granules of neutrophils and is released when the neutrophils are activated. It can also be found in the lysosomes of monocytes[13]. MPO expression is not, however, restricted to neutrophils and monocytes. For example, endothelial cells can produce MPO when oxidative stress is induced by non-lethal doses of hydrogen peroxide (H2O2)[14]. MPO uses H2O2 and chloride ions (Cl−) to produce hypochlorous acid (HOCl)[15]. HOCl is a powerful oxidant and participates in the microbicidal activity of MPO by oxidizing molecules from the pathogen membrane. Some other (pseudo-)halogenous oxidants can be synthesized by MPO, such as hypobromous acid (HOBr) or hypothiocyanous acid (HOSCN)[16]. HOCl is thought to be the most abundant product because of the availability of chloride ions in the extracellular medium, but it should be noted that thiocyanate (SCN−) is a better substrate for MPO and that in patients with high SCN− levels, such as smokers, the concentrations of HOSCN produced will be significantly higher[17]. As a matter of fact, MPO has several roles in major events in atherosclerosis such as endothelial dysfunction, atherosclerotic plaque destabilization, and lipoprotein oxidation

2.1. Endothelial Dysfunction

MPO seems to act at all stages of atherosclerosis. A correlation has been established between MPO activity and endothelial dysfunction. Cheng et al.[18] pharmacologically inhibited MPO in mice and observed improved endothelial function in two different inflammatory models. The endothelium reacts as a selective barrier, regulating vascular tone, angiogenesis, inflammation, and platelet activation and adhesion. When the endothelium no longer fulfills its functions correctly, endothelial dysfunction occurs[19]. Nitric oxide (•NO) is produced by endothelial NO synthase (eNOS) in endothelial cells and is a key mediator in the maintenance of homeostasis[20]. By reducing •NO bioavailability, MPO promotes endothelial dysfunction. First, •NO can be directly consumed by MPO[21]. Second, the production of •NO is reduced in the presence of MPO and its products. Indeed, in vitro, HOCl causes an uncoupling of eNOS that makes the production of •NO impossible[22]. HOCl also chlorinates L-arginine, the physiological substrate of eNOS for •NO production and the chlorinated L-arginine inhibits endothelial •NO synthesis in a rat model[23].

2.2. Plaque Destabilization

MPO is also involved in plaque destabilization via the production of HOCl. During the development of the atheromatous plaque, smooth muscle cells migrate to the intima and synthesize extracellular matrix components to form a fibrous cap that isolates the plaque lipid core from the bloodstream[24]. HOCl could act on the fibrous cap by modulating matrix metalloproteinase (MMPs) activity. MMPs degrade the extracellular matrix components of the plaque such as collagen [25][26][27][28].

2.3. Lipoprotein Oxidation

One of the most studied roles of MPO in atherosclerosis is its involvement in the modification of lipoproteins. It has been almost 30 years since the presence of MPO in human atherosclerotic plaques was demonstrated by Daugherty et al.[29] and its role in lipoprotein oxidation has been studied ever since. Numerous studies have highlighted the ability of MPO to oxidize LDL and have confirmed the presence of these modified LDLs in human atherosclerotic lesions[30][31][32]. Oxidized LDLs play an important role in the development of the atheromatous plaque[33]. As previously stated, MPO generates HOCl, which reacts with molecules such as the protein moiety of LDL, apolipoproteinB-100 (apoB-100)[34]. MPO can bind LDLs. This binding is most likely mediated by ionic interactions because MPO is a cationic enzyme[35]. Several studies have demonstrated a difference between HOCl-oxidized LDLs (HOCl-LDLs) and Mox-LDLs[36][37]. With its ability to interact with both LDLs and endothelial cells, MPO can oxidize LDLs in the bloodstream at the surface of the endothelial cell[38]. Oxidized-LDLs are internalized by macrophages. The lipid-laden macrophages are then considered to be foam cells which accumulate in the intima and form the fatty streaks. The fatty streaks then evolve into an atherosclerotic plaque[24]. It is noteworthy that MPO is also able to oxidize HDLs[10].

3. Mox-LDL-Cell Interactions

3.1. Mox-LDL-Macrophages

In addition to their role in the formation of foam cells, Mox-LDLs interact with various cell types involved in the development of atherosclerosis, such as macrophages and endothelial cells. When THP-1 cells were incubated with Mox-LDLs, an increase in TNF-α secretion was observed[39]. Calay et al. [40] incubated RAW264.7 and peripheral blood mononuclear cell (PMBC)-derived macrophages with Mox-LDLs and confirmed an intracellular increase in ROS, which was mediated by cytosolic phospholipase A2 (cPLA2). Mox-LDLs play a role in macrophage polarization. Macrophages express different phenotypes depending on their environment. These phenotypes are generally divided into two groups: M1 macrophages, which are pro-inflammatory, and M2 macrophages, which are anti-inflammatory. The M1-M2 classification is, however, inadequate because it represents two extremities, whereas macrophages probably have more nuanced phenotypes. When unpolarized RAW264.7 macrophages were incubated with Mox-LDLs, the expression of the marker genes increased for both M1 and M2 macrophages, but these Mox-LDL-stimulated macrophages tended to have an intermediate phenotype, which was more anti-inflammatory[41].

3.2. Mox-LDL-Endothelial Cells

Endothelial cells maintain a balance between coagulation and fibrinolysis. Incubation with Mox-LDLs disrupts the fibrin clot elimination at the endothelial cell surface. A hypofibrinolytic state has been demonstrated in patients with atherosclerosis and the accumulation of fibrin at the endothelial cell surface increases endothelial permeability, which enables the accumulation of lipids in the subendothelial space and the formation of foam cells[42]. Oxidized LDL has often been considered a source of oxidative stress, and, indeed, copper-oxidized LDLs induce oxidative stress in endothelial cells[43]. However, copper-oxidized LDLs and Mox-LDLs have different effects, and it has been shown that Mox-LDLs do not induce ROS production by human aortic endothelial cells (HAEC)[44]. Another effect of Mox-LDLs on the endothelium has been demonstrated in vitro on angiogenesis. The interaction of Mox-LDLs with endothelial cells decreases their motility, their tubulogenesis, and their migration[45]. While studying the effect of Mox-LDLs on endothelial cells, Dufour et al.[46] noticed that the extracellular concentration of resolvin D1 (RvD1) increased rapidly after stimulation with Mox-LDLs and native LDLs (Nat-LDLs) with a synergistic action in these LDLs. The relationship between Mox-LDLs and RvD1 needs to be further studied given that the only existing information at the moment comes from an in vitro model on endothelial cells. The hypothesis that the stimulation of SPM production by Mox-LDLs may help compensate for the deleterious effect of Mox-LDLs in vivo remains to be proven. The pathways by which Mox-LDLs interact with endothelial cells are largely undetermined and appear to be diversified. Recently, El-Hajjar et al.[47] demonstrated that Mox-LDLs exert pro-inflammatory activity on HAECs by stimulating IL-8 production through the scavenger receptor LOX-1. In contrast, RvD1 production by endothelial cells is not dependent on LOX-1 and involves other pathways that are not fully understood[48].

4. Bioactive Lipid Mediators: Implications in Atherosclerosis

Pro-inflammatory mediators, such as prostaglandins or leukotrienes, are produced by immune cells in the first stages of acute inflammation. Those mediators are synthesized very rapidly from arachidonic acid by cyclooxygenases or lipoxygenases, within seconds of the onset of inflammation. Depending on the cytokines and signals perceived in the environment, leukocytes can move from the production of these pro-inflammatory mediators to the production of pro-resolving mediators, such as lipoxins and resolvins, resulting in a temporal switch in mediator profiles[49]. This process generates lipid mediators by successive oxidations from n-6 polyunsaturated fatty acid (PUFA) and from n-3 PUFAs[50]. Lipoxin, resolvin, protectin, and maresin are part of the so-called SPMs[51]. Extensively studied since 2000, these SPMs are potent inhibitors of human polymorphonuclear (PMN) leukocyte transendothelial migration and infiltration at picogram-to-nanogram concentrations. They enhance monocyte/macrophage clearance of cellular debris and apoptotic PMNs, which is required for tissue homeostasis[52][53]. Lipoxin A4, a SPM derived from arachidonic acid, downregulates azurophilic degranulation of stimulated PMNs and, by doing so, decreases MPO activity[54]. RvD1 is a bioactive molecule derived from docosahexaenoic acid (DHA). After two oxidations by 15-lipoxygenase (15-LOX) and by 5-lipoxygenase (5-LOX), 7S-hydroperoxy-17S-HDHA is produced. This intermediate is converted into epoxide and then undergoes enzymatic hydrolysis to obtain RvD1[55]. RvD1 acts locally at the site of inflammation by binding to two receptors: the lipoxin A4 receptor, ALX, and an orphan receptor coupled to a G-protein, the GPR32. Both receptors are found on the surface of phagocytes. When RvD1 binds to these receptors, it promotes phagocytosis, which is essential for the resolution of inflammation[56]. RvD1 also stimulates the synthesis of another SPM, lipoxin B4, and decreases that of leukotriene B4 (LTB4) in an ALX-dependent manner in mice[57]. Various aspects of RvD1 being potentially involved in the modulation of atherosclerosis have been studied. First, the level of RvD1 in highly necrotic atherosclerotic plaques was shown to be defective in humans and these plaques showed a marked imbalance between RvD1 and LTB4 [3]. The RvD1:LTB4 ratio measured in human salivary samples was proposed as a potential predictor of atherosclerosis, taking into account the correlation observed with carotid intima media thickness[58]. Second, interventional studies were conducted to evaluate the effects of RvD1. When neutrophils were exposed to RvD1, interactions with the endothelium decreased significantly in a concentration-dependent manner [56]. In addition, RvD1 decreased the expression of adhesion molecules in inflammatory conditions, such as vascular cell adhesion molecule 1 (VCAM-1), which decreases the interactions of macrophages with the endothelium[59]. Treatment with RvD1 also increased pro-resolving markers, such as arginase 1 and mannose receptor C-type 1, in macrophages and regulated leukocyte function and plasticity[60]. The effects of RvD1 on endothelial permeability have also been explored. RvD1 maintained endothelial cell integrity by preventing lipopolysaccharide-mediated barrier functions[61]. RvD1 enhanced efferocytosis, a critical cellular process of inflammation resolution that is defective in atherosclerosis[62][63].

5. Monocyte-Derived Macrophages and SPMs: Interplay in Atherosclerosis

Macrophages play a critical role in atherosclerosis progression, responding to various environmental signals, including bioactive lipid-derived, and adapting their phenotype over time. Macrophage phenotype diversity and its role in atherosclerosis were summareviewized recently by Jinnouchi et al[64]. In human atherosclerotic lesions, macrophage subpopulations have been identified and were more numerous in symptomatic plaques[65][66]. Cho et al.[66] showed that M1 macrophages were dominant within unstable carotid plaques. Pireaux et al.[67] highlighted the importance of the disease-related environment in macrophage polarization. They observed a higher percentage of M2 monocytes in the plasma of hemodialysis patients than in the controls. In contrast, the concentrations of inflammatory biomarkers—such as CRP, macrophage-colony stimulating factor (M-CSF), and IL-8, as well as chloro-tyrosine and homocitrulline—which are markers of myeloperoxidase-associated oxidative stress, were positively correlated with the M2 phenotype[67]. RvD1 was negatively correlated with M1 macrophage levels but not with M2 levels in patients undergoing hemodialysis[46]. These results suggest a more complex interaction of pro-inflammatory and pro-resolving mediators in self-regulation and macrophage polarization than expected. Indeed, RvD1 and the intermediary 17-HDHA promote polarization toward an anti-inflammatory M2-phenotype[68][69]. Furthermore, other lipid mediators, such as nitrosylated-fatty acids and n-3 PUFA products, polarize plaque macrophages toward anti-inflammatory and pro-resolving phenotypes, thereby confirming the complex dual role of these cells[70]. Macrophages possess distinct lipid mediator profiles according to their phenotype. Indeed, the comparison of endogenous mediator biosynthesis in M1 and M2 macrophages provides some insight. M2 macrophages produce maresin 1 and RvD5, both derived from DHA, as well as resolvin E2 (RvE2) and lipoxins. Conversely, M1 macrophages biosynthesize cyclooxygenase-derived lipid mediators such as prostaglandin E2, prostaglandin F2 , and thromboxane B2[71]. In an experiment conducted by Dalli et al.[71], the phagocytosis of apoptotic PMNs by macrophages—in other words, efferocytosis—stimulated SPM production. Of interest, the activation of the MerTK receptor, a macrophage receptor involved in the process of efferocytosis, upregulated SPM production by increasing the cytoplasmic/ nuclear ratio of a key SPM biosynthetic enzyme, 5-LOX[72].

6. Conclusions

Atherosclerotic plaques are a battlefield of pro-inflammatory and pro-resolving factors with a particular interplay of monocyte-derived macrophages. MPO is one of the leading agents inducing oxidative stress and is the basis for Mox-LDL generation. These particular LDLs, which are closer to physiological conditions than ox-LDLs, have a double-sided effect in inflammation. Mox-LDLs modulate the SPM/pro-inflammatory balance by promoting RvD1 and IL-8 at the endothelial level, suggesting a crucial role in the development and stabilization of the atheromatous plaque. During oxidative stress regulation, the induction of SPMs and the M2 macrophage phenotype is a matter of survival. The defective resolution of inflammation at all stages of vascular inflammation has led to the proposal of the resolvin/leukotriene ratio as a relevant biomarker in atherosclerosis. In addition, SPMs such as resolvin D1 successfully prevented atheroprogression in pre-clinical models. However, the role of MPO, and, more specifically, Mox-LDLs in the production of SPMs by endothelial cells and macrophages is not well established and opens the field to future research on their roles in the resolution of inflammation.

References

  1. Falk, E.; Pathogenesis of Atherosclerosis. J. Am. Coll. Cardiol. 2006, 47, C7-C12.
  2. Bäck, M.; Yurdagul, A.; Tabas, I.; Öörni, K.; Kovanen, P.T.; nflammation and Its Resolution in Atherosclerosis: Mediators and Therapeutic Opportunities.. Nat. Rev. Cardiol. 2019, 16, 389-406.
  3. Gabrielle Fredman; Jason Hellmann; Jonathan D. Proto; George Kuriakose; Romain A. Colas; Bernhard Dorweiler; E. Sander Connolly; Robert Solomon; David M. Jones; Eric J. Heyer; et al.Matthew SpiteIra Tabas An imbalance between specialized pro-resolving lipid mediators and pro-inflammatory leukotrienes promotes instability of atherosclerotic plaques. Nature Communications 2016, 7, 12859, 10.1038/ncomms12859.
  4. Gabrielle Fredman; Can Inflammation-Resolution Provide Clues to Treat Patients According to Their Plaque Phenotype?. Frontiers in Pharmacology 2019, 10, 205, 10.3389/fphar.2019.00205.
  5. Gabrielle Fredman; Ira Tabas; Boosting Inflammation Resolution in Atherosclerosis. The American Journal of Pathology 2017, 187, 1211-1221, 10.1016/j.ajpath.2017.01.018.
  6. Fadia A. Mayyas; Mohammad I. Al-Jarrah; Khalid S. Ibrahim; Karem Alzoubi; Level and significance of plasma myeloperoxidase and the neutrophil to lymphocyte ratio in patients with coronary artery disease. Experimental and Therapeutic Medicine 2014, 8, 1951-1957, 10.3892/etm.2014.2034.
  7. Amjad A. Khan; Mohammed A. Alsahli; Arshad H. Rahmani; Myeloperoxidase as an Active Disease Biomarker: Recent Biochemical and Pathological Perspectives. Medical Sciences 2018, 6, 33, 10.3390/medsci6020033.
  8. Renliang Zhang; Marie-Luise Brennan; XiaoMing Fu; Ronnier J. Aviles; Gregory L. Pearce; Marc S. Penn; Eric Topol; Dennis L. Sprecher; Stanley L. Hazen; Association Between Myeloperoxidase Levels and Risk of Coronary Artery Disease. JAMA 2001, 286, 2136-2142, 10.1001/jama.286.17.2136.
  9. Hiroshi Yoshida; Reiko Kisugi; Mechanisms of LDL oxidation. Clinica Chimica Acta 2010, 411, 1875-1882, 10.1016/j.cca.2010.08.038.
  10. Baohai Shao; Michael N. Oda; John F. Oram; Jay W. Heinecke; Myeloperoxidase: An Oxidative Pathway for Generating Dysfunctional High-Density Lipoprotein. Chemical Research in Toxicology 2009, 23, 447-454, 10.1021/tx9003775.
  11. Gjin Ndrepepa; Myeloperoxidase – A bridge linking inflammation and oxidative stress with cardiovascular disease. Clinica Chimica Acta 2019, 493, 36-51, 10.1016/j.cca.2019.02.022.
  12. Karim Zouaoui Boudjeltia; Ilham Legssyer; Pierre Van Antwerpen; Roger Lema Kisoka; Sajida Babar; Nicole Moguilevsky; Paul Delree; Jean Ducobu; Claude Remacle; Michel Vanhaeverbeek; et al.Dany Brohee Triggering of inflammatory response by myeloperoxidase-oxidized LDLAn oral presentation of the data was given before the Congress of the Beligian Society of Internal Medicine.. Biochemistry and Cell Biology 2006, 84, 805-812, 10.1139/o06-061.
  13. Yasuaki Aratani; Myeloperoxidase: Its role for host defense, inflammation, and neutrophil function. Archives of Biochemistry and Biophysics 2018, 640, 47-52, 10.1016/j.abb.2018.01.004.
  14. Giampiero La Rocca; Antonino Di Stefano; Ermanno Eleuteri; Rita Anzalone; Francesca Magno; Simona Corrao; Tiziana Loria; Anna Martorana; Claudio Di Gangi; Marilena Colombo; et al.Fabrizio SansoneFrancesco PatanèFelicia FarinaMauro RinaldiFrancesco CappelloPantaleo GiannuzziGiovanni Zummo Oxidative stress induces myeloperoxidase expression in endocardial endothelial cells from patients with chronic heart failure. Basic Research in Cardiology 2008, 104, 307-320, 10.1007/s00395-008-0761-9.
  15. J E Harrison; J Schultz; Studies on the chlorinating activity of myeloperoxidase.. Journal of Biological Chemistry 1976, 251, 1371-1374, 10.1016/s0021-9258(17)33749-3.
  16. Tony Kettle; C. C. Winterbourn; Myeloperoxidase: a key regulator of neutrophil oxidant production. Redox Report 1997, 3, 3-15, 10.1080/13510002.1997.11747085.
  17. David I. Pattison; Michael J. Davies; Clare L. Hawkins; Reactions and reactivity of myeloperoxidase-derived oxidants: Differential biological effects of hypochlorous and hypothiocyanous acids. Free Radical Research 2012, 46, 975-995, 10.3109/10715762.2012.667566.
  18. David Cheng; Jihan Talib; Christopher P. Stanley; Imran Rashid; Erik Michaëlsson; Eva-Lotte Lindstedt; Kevin Croft; Tony Kettle; Ghassan J. Maghzal; Roland Stocker; et al. Inhibition of MPO (Myeloperoxidase) Attenuates Endothelial Dysfunction in Mouse Models of Vascular Inflammation and Atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology 2019, 39, 1448-1457, 10.1161/atvbaha.119.312725.
  19. Suowen Xu; Iqra Ilyas; Peter J. Little; Hong Li; Danielle Kamato; Xueying Zheng; Sihui Luo; Zhuoming Li; Peiqing Liu; Jihong Han; et al.Ian C. HardingEno E. EbongScott J. CameronAlastair G. StewartJianping Weng Endothelial Dysfunction in Atherosclerotic Cardiovascular Diseases and Beyond: From Mechanism to Pharmacotherapies. Pharmacological Reviews 2021, 73, 924-967, 10.1124/pharmrev.120.000096.
  20. U Förstermann; E I Closs; J S Pollock; M Nakane; P Schwarz; I Gath; H Kleinert; Nitric oxide synthase isozymes. Characterization, purification, molecular cloning, and functions.. Hypertension 1994, 23, 1121-1131, 10.1161/01.hyp.23.6.1121.
  21. Jason P. Eiserich; Stephan Baldus; Marie-Luise Brennan; Stephen L. Hoffman; Chunxiang Zhang; Albert Tousson; Laura Castro; Aldons J. Lusis; William M. Nauseef; C. Roger White; et al.Bruce A. Freeman Myeloperoxidase, a Leukocyte-Derived Vascular NO Oxidase. Science 2002, 296, 2391-2394, 10.1126/science.1106830.
  22. Jian Xu; Zhonglin Xie; Richard Reece; David Pimental; Ming-Hui Zou; Uncoupling of Endothelial Nitric Oxidase Synthase by Hypochlorous Acid. Arteriosclerosis, Thrombosis, and Vascular Biology 2006, 26, 2688-2695, 10.1161/01.atv.0000249394.94588.82.
  23. Chunxiang Zhang; Chris Reiter; Jason P. Eiserich; Brenda Boersma; Dale A. Parks; Joseph S. Beckman; Stephen Barnes; Marion Kirk; Stephan Baldus; Victor Darley-Usmar; et al.C. Roger White l-Arginine Chlorination Products Inhibit Endothelial Nitric Oxide Production. Journal of Biological Chemistry 2001, 276, 27159-27165, 10.1074/jbc.m100191200.
  24. Mahmoud Rafieian-Kopaei; Mahbubeh Setorki; Monir Doudi; Azar Baradaran; Hamid Nasri; Atherosclerosis: Process, Indicators, Risk Factors and New Hopes. International Journal of Preventive Medicine 2014, 5, 927-946.
  25. Yi Wang; Henry Rosen; David K. Madtes; Baohai Shao; Thomas R. Martin; Jay W. Heinecke; Xiaoyun Fu; Myeloperoxidase Inactivates TIMP-1 by Oxidizing Its N-terminal Cysteine Residue. Journal of Biological Chemistry 2007, 282, 31826-31834, 10.1074/jbc.m704894200.
  26. S. J. Weiss; G. Peppin; X. Ortiz; C. Ragsdale; S. T. Test; Oxidative Autoactivation of Latent Collagenase by Human Neutrophils. Science 1985, 227, 747-749, 10.1126/science.2982211.
  27. G J Peppin; S J Weiss; Activation of the endogenous metalloproteinase, gelatinase, by triggered human neutrophils.. Proceedings of the National Academy of Sciences 1986, 83, 4322-4326, 10.1073/pnas.83.12.4322.
  28. Xiaoyun Fu; Sean Y. Kassim; William C. Parks; Jay W. Heinecke; Hypochlorous Acid Oxygenates the Cysteine Switch Domain of Pro-matrilysin (MMP-7). Journal of Biological Chemistry 2001, 276, 41279-41287, 10.1074/jbc.m106958200.
  29. A Daugherty; J L Dunn; D L Rateri; J W Heinecke; Myeloperoxidase, a catalyst for lipoprotein oxidation, is expressed in human atherosclerotic lesions.. Journal of Clinical Investigation 1994, 94, 437-444, 10.1172/jci117342.
  30. L J Hazell; L Arnold; D Flowers; G Waeg; E Malle; R Stocker; Presence of hypochlorite-modified proteins in human atherosclerotic lesions.. Journal of Clinical Investigation 1996, 97, 1535-1544, 10.1172/jci118576.
  31. Anitra C. Carr; Mark R. McCall; Balz Frei; Oxidation of LDL by Myeloperoxidase and Reactive Nitrogen Species. Arteriosclerosis, Thrombosis, and Vascular Biology 2000, 20, 1716-1723, 10.1161/01.atv.20.7.1716.
  32. Ernst Malle; Georg Waeg; Renate Schreiber; Elisabeth F. Gröne; Wolfgang Sattler; Hermann-Josef Gröne; Immunohistochemical evidence for the myeloperoxidase/H2O2/halide system in human atherosclerotic lesions. JBIC Journal of Biological Inorganic Chemistry 2000, 267, 4495-4503, 10.1046/j.1432-1327.2000.01498.x.
  33. Giuseppe Maiolino; Giacomo Rossitto; Paola Caielli; Valeria Bisogni; Gian Paolo Rossi; Lorenzo A. Calò; The Role of Oxidized Low-Density Lipoproteins in Atherosclerosis: The Myths and the Facts. Mediators of Inflammation 2013, 2013, 1-13, 10.1155/2013/714653.
  34. N. Moguilevsky; K. Zouaoui Boudjeltia; S. Babar; P. Delrée; I. Legssyer; Y. Carpentier; M. Vanhaeverbeek; J. Ducobu; Monoclonal antibodies against LDL progressively oxidized by myeloperoxidase react with ApoB-100 protein moiety and human atherosclerotic lesions. Biochemical and Biophysical Research Communications 2004, 323, 1223-1228, 10.1016/j.bbrc.2004.08.220.
  35. Anitra C. Carr; Melinda C. Myzak; Roland Stocker; Mark R. McCall; Balz Frei; Myeloperoxidase binds to low-density lipoprotein: potential implications for atherosclerosis. FEBS Letters 2000, 487, 176-180, 10.1016/s0014-5793(00)02227-4.
  36. Delporte, C.; Boudjeltia, K.Z.; Noyon, C.; Furtmüller, P.G.; Nuyens, V.; Slomianny, M.-C.; Madhoun, P.; Desmet, J.-M.; Raynal, P.; Dufour, D.; et al.et al Impact of Myeloperoxidase-LDL Interactions on Enzyme Activity and Subsequent Posttranslational Oxidative Modifications of ApoB-100.. J. Lipid Res. 2014, 55, 747-757.
  37. Chao-Yuh Yang; Zi-Wei Gu; Manlan Yang; Shen-Nan Lin; Anthony J. Garcia-Prats; Lynette K. Rogers; Stephen E. Welty; Charles V. Smith; Selective modification of apoB-100 in the oxidation of low density lipoproteins by myeloperoxidase in vitro. Journal of Lipid Research 1999, 40, 686-698, 10.1016/s0022-2275(20)32148-9.
  38. K. Zouaoui Boudjeltia; N. Moguilevsky; I. Legssyer; S. Babar; M. Guillaume; P. Delree; M. Vanhaeverbeek; D. Brohee; J. Ducobu; C. Remacle; et al. Oxidation of low density lipoproteins by myeloperoxidase at the surface of endothelial cells: an additional mechanism to subendothelium oxidation. Biochemical and Biophysical Research Communications 2004, 325, 434-438, 10.1016/j.bbrc.2004.10.049.
  39. Cédric Delporte; Pierre Van Antwerpen; Luc Vanhamme; Thierry Roumeguère; Karim Zouaoui Boudjeltia; Low-Density Lipoprotein Modified by Myeloperoxidase in Inflammatory Pathways and Clinical Studies. Mediators of Inflammation 2013, 2013, 1-18, 10.1155/2013/971579.
  40. Damien Calay; Alexandre Rousseau; Laurine Mattart; Vincent Nuyens; Cédric Delporte; Pierre Van Antwerpen; Nicole Moguilevsky; Thierry Arnould; Karim Zouaoui Boudjeltia; Martine Raes; et al. Copper and Myeloperoxidase-Modified LDLs Activate Nrf2 Through Different Pathways of ROS Production in Macrophages. Antioxidants & Redox Signaling 2010, 13, 1491-1502, 10.1089/ars.2009.2971.
  41. Valérie Pireaux; Aude Sauvage; Benoî Bihin; Martine Van Steenbrugge; Alexandre Rousseau; Pierre Van Antwerpen; Karim Zouaoui Boudjeltia; Martine Raes; Myeloperoxidase-Oxidized LDLs Enhance an Anti-Inflammatory M2 and Antioxidant Phenotype in Murine Macrophages. Mediators of Inflammation 2016, 2016, 1-20, 10.1155/2016/8249476.
  42. Karim Zouaoui Boudjeltia; Jalil Daher; Pierre Van Antwerpen; Nicole Moguilevsky; Paul Delree; Jean Ducobu; Martine Raes; Bassam Badran; Michel Vanhaeverbeek; Dany Brohée; et al.Claude RemacleLuc Vanhamme Exposure of Endothelial Cells to Physiological Levels of Myeloperoxidase-Modified LDL Delays Pericellular Fibrinolysis. PLOS ONE 2012, 7, e38810, 10.1371/journal.pone.0038810.
  43. Alexandra Heinloth; Kathrin Heermeier; Ulrike Raff; Christoph Wanner; Jan Galle; Stimulation of NADPH Oxidase by Oxidized Low-Density Lipoprotein Induces Proliferation of Human Vascular Endothelial Cells. Journal of the American Society of Nephrology 2000, 11, 1819-1825, 10.1681/asn.v11101819.
  44. Ghadir El Samad; Samer Bazzi; Marc Karam; Karim Zouaoui Boudjeltia; Luc Vanhamme; Jalil Daher; Effect of myeloperoxidase modified LDL on bovine and human aortic endothelial cells. Experimental and Therapeutic Medicine 2019, 18, 4567-4574, 10.3892/etm.2019.8109.
  45. Jalil Daher; Maud Martin; Alexandre Rousseau; Vincent Nuyens; Hussein Fayyad-Kazan; Pierre Van Antwerpen; Guy Courbebaisse; Philippe Martiat; Bassam Badran; Frank Dequiedt; et al.Karim Zouaoui BoudjeltiaLuc Vanhamme Myeloperoxidase Oxidized LDL Interferes with Endothelial Cell Motility through miR-22 and Heme Oxygenase 1 Induction: Possible Involvement in Reendothelialization of Vascular Injuries. Mediators of Inflammation 2014, 2014, 1-14, 10.1155/2014/134635.
  46. Damien Dufour; Alia Khalil; Vincent Nuyens; Alexandre Rousseau; Cédric Delporte; Caroline Noyon; Melissa Cortese; Florence Reyé; Valérie Pireaux; Jean Nève; et al.Luc VanhammeBernard RobayeChristophe LelubreJean-Marc DesmetMartine RaesKarim Zouaoui BoudjeltiaPierre Van Antwerpen Native and myeloperoxidase-oxidized low-density lipoproteins act in synergy to induce release of resolvin-D1 from endothelial cells. Atherosclerosis 2018, 272, 108-117, 10.1016/j.atherosclerosis.2018.03.012.
  47. Layal El-Hajjar; Judy Hindieh; Rana Andraos; Marwan El-Sabban; Jalil Daher; Myeloperoxidase-Oxidized LDL Activates Human Aortic Endothelial Cells through the LOX-1 Scavenger Receptor. International Journal of Molecular Sciences 2022, 23, 2837, 10.3390/ijms23052837.
  48. Damien Dufour; Alia Khalil; Vincent Nuyens; Alexandre Rousseau; Cédric Delporte; Caroline Noyon; Melissa Cortese; Florence Reyé; Valérie Pireaux; Jean Nève; et al.Luc VanhammeBernard RobayeChristophe LelubreJean-Marc DesmetMartine RaesKarim Zouaoui BoudjeltiaPierre Van Antwerpen Data on myeloperoxidase-oxidized low-density lipoproteins stimulation of cells to induce release of resolvin-D1. Data in Brief 2018, 18, 1160-1171, 10.1016/j.dib.2018.03.131.
  49. Charles N. Serhan; Nan Chiang; Thomas E. Van Dyke; Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nature Reviews Immunology 2008, 8, 349-361, 10.1038/nri2294.
  50. Nan Chiang; Charles N. Serhan; Specialized pro-resolving mediator network: an update on production and actions. Essays in Biochemistry 2020, 64, 443-462, 10.1042/ebc20200018.
  51. Undurti N. Das; Bioactive Lipids in Age-Related Disorders. null 2020, 1260, 33-83, 10.1007/978-3-030-42667-5_3.
  52. Charles N. Serhan; Clary Clish; Jessica Brannon; Sean P. Colgan; Nan Chiang; Karsten Gronert; Novel Functional Sets of Lipid-Derived Mediators with Antiinflammatory Actions Generated from Omega-3 Fatty Acids via Cyclooxygenase 2–Nonsteroidal Antiinflammatory Drugs and Transcellular Processing. Journal of Experimental Medicine 2000, 192, 1197-1204, 10.1084/jem.192.8.1197.
  53. Charles N. Serhan; Bruce D. Levy; Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators. Journal of Clinical Investigation 2018, 128, 2657-2669, 10.1172/jci97943.
  54. Andrew T. Gewirtz; Valery V. Fokin; Nicos A. Petasis; Charles N. Serhan; James L. Madara; LXA4, aspirin-triggered 15-epi-LXA4, and their analogs selectively downregulate PMN azurophilic degranulation. American Journal of Physiology-Cell Physiology 1999, 276, C988-C994, 10.1152/ajpcell.1999.276.4.c988.
  55. Yee-Ping Sun; Sungwhan F. Oh; Jasim Uddin; Rong Yang; Katherine Gotlinger; Eric Campbell; Sean P. Colgan; Nicos Petasis; Charles N. Serhan; Resolvin D1 and Its Aspirin-triggered 17R Epimer. Journal of Biological Chemistry 2007, 282, 9323-9334, 10.1074/jbc.m609212200.
  56. Sriram Krishnamoorthy; Antonio Recchiuti; Nan Chiang; Stephanie Yacoubian; Chih-Hao Lee; Rong Yang; Nicos A. Petasis; Charles N. Serhan; Resolvin D1 binds human phagocytes with evidence for proresolving receptors. Proceedings of the National Academy of Sciences 2010, 107, 1660-1665, 10.1073/pnas.0907342107.
  57. Lucy V. Norling; Jesmond Dalli; Roderick J. Flower; Charles N. Serhan; Mauro Perretti; Resolvin D1 Limits Polymorphonuclear Leukocyte Recruitment to Inflammatory Loci. Arteriosclerosis, Thrombosis, and Vascular Biology 2012, 32, 1970-1978, 10.1161/atvbaha.112.249508.
  58. Silke Thul; Carlos Labat; Mohamed Temmar; Athanase Benetos; Magnus Bäck; Low salivary resolvin D1 to leukotriene B4 ratio predicts carotid intima media thickness: A novel biomarker of non-resolving vascular inflammation. European Journal of Preventive Cardiology 2017, 24, 903-906, 10.1177/2047487317694464.
  59. Aimeé Salas-Hernández; Claudio Espinoza-Pérez; Raúl Vivar; Jenaro Espitia-Corredor; José Lillo; Pablo Parra-Flores; Carlos F. Sánchez-Ferrer; Concepción Peiró; Guillermo Díaz-Araya; Resolvin D1 and E1 promote resolution of inflammation in rat cardiac fibroblast in vitro. Molecular Biology Reports 2021, 48, 57-66, 10.1007/s11033-020-06133-8.
  60. Vasundhara Kain; Ganesh V. Halade; Immune responsive resolvin D1 programs peritoneal macrophages and cardiac fibroblast phenotypes in diversified metabolic microenvironment. Journal of Cellular Physiology 2018, 234, 3910-3920, 10.1002/jcp.27165.
  61. Rima Chattopadhyay; Somasundaram Raghavan; Gadiparthi N. Rao; Resolvin D1 via prevention of ROS-mediated SHP2 inactivation protects endothelial adherens junction integrity and barrier function. Redox Biology 2017, 12, 438-455, 10.1016/j.redox.2017.02.023.
  62. Nicholas Rymut; Justin Heinz; Sudeshna Sadhu; Zeinab Hosseini; Colin O. Riley; Michael Marinello; Jackson Maloney; Katherine C. MacNamara; Matthew Spite; Gabrielle Fredman; et al. Resolvin D1 promotes efferocytosis in aging by limiting senescent cell‐induced MerTK cleavage. The FASEB Journal 2019, 34, 597-609, 10.1096/fj.201902126r.
  63. Ira Tabas; Guillermo García-Cardeña; Gary K. Owens; Recent insights into the cellular biology of atherosclerosis. Journal of Cell Biology 2015, 209, 13-22, 10.1083/jcb.201412052.
  64. Hiroyuki Jinnouchi; Liang Guo; Atsushi Sakamoto; Sho Torii; Yu Sato; Anne Cornelissen; Salome Kuntz; Ka Hyun Paek; Raquel Fernandez; Daniela Fuller; et al.Neel GadhokeDipti SurveMaria RomeroFrank D. KolodgieRenu VirmaniAloke V. Finn Diversity of macrophage phenotypes and responses in atherosclerosis. Cellular and Molecular Life Sciences 2019, 77, 1919-1932, 10.1007/s00018-019-03371-3.
  65. Stephen W. Waldo; Yifu Li; Chiara Buono; Bin Zhao; Eric M. Billings; Janet Chang; Howard S. Kruth; Heterogeneity of Human Macrophages in Culture and in Atherosclerotic Plaques. The American Journal of Pathology 2008, 172, 1112-1126, 10.2353/ajpath.2008.070513.
  66. Kyu Yong Cho; Hideaki Miyoshi; Satoshi Kuroda; Hiroshi Yasuda; Kenji Kamiyama; Joji Nakagawara; Masayoshi Takigami; Takuma Kondo; Tatsuya Atsumi; The Phenotype of Infiltrating Macrophages Influences Arteriosclerotic Plaque Vulnerability in the Carotid Artery. Journal of Stroke and Cerebrovascular Diseases 2012, 22, 910-918, 10.1016/j.jstrokecerebrovasdis.2012.11.020.
  67. Valérie Pireaux; Cédric Delporte; Alexandre Rousseau; Jean-Marc Desmet; Pierre Van Antwerpen; Martine Raes; Karim Zouaoui Boudjeltia; M2 Monocyte Polarization in Dialyzed Patients Is Associated with Increased Levels of M-CSF and Myeloperoxidase-Associated Oxidative Stress: Preliminary Results. Biomedicines 2021, 9, 84, 10.3390/biomedicines9010084.
  68. Jesmond Dalli; Min Zhu; Nikita A. Vlasenko; Bin Deng; Jesper Z. Haeggström; Nicos A. Petasis; Charles N. Serhan; The novel 13S,14S‐epoxy‐maresin is converted by human macrophages to maresin 1 (MaR1), inhibits leukotriene A4hydrolase (LTA4H), and shifts macrophage phenotype. The FASEB Journal 2013, 27, 2573-2583, 10.1096/fj.13-227728.
  69. Cheng-Ying Chiu; Beate Gomolka; Cordula Dierkes; Nora R. Huang; Maik Schroeder; Martin Purschke; Dieter Manstein; Bindi Dangi; Karsten H. Weylandt; Omega-6 docosapentaenoic acid-derived resolvins and 17-hydroxydocosahexaenoic acid modulate macrophage function and alleviate experimental colitis. Inflammation Research 2012, 61, 967-976, 10.1007/s00011-012-0489-8.
  70. Samantha Adamson; Norbert Leitinger; Phenotypic modulation of macrophages in response to plaque lipids. Current Opinion in Lipidology 2011, 22, 335-342, 10.1097/mol.0b013e32834a97e4.
  71. Jesmond Dalli; Charles N. Serhan; Specific lipid mediator signatures of human phagocytes: microparticles stimulate macrophage efferocytosis and pro-resolving mediators. Blood 2012, 120, e60-e72, 10.1182/blood-2012-04-423525.
  72. Bishuang Cai; Edward B. Thorp; Amanda C. Doran; Manikandan Subramanian; Brian E. Sansbury; Chyuan-Sheng Lin; Matthew Spite; Gabrielle Fredman; Ira Tabas; MerTK cleavage limits proresolving mediator biosynthesis and exacerbates tissue inflammation. Proceedings of the National Academy of Sciences 2016, 113, 6526-6531, 10.1073/pnas.1524292113.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)
Video Production Service
Feedback