Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Marios Sagris
 + 2421 word(s) 2421 2021-06-28 10:01:01 |
2 format correct
Conner Chen
 Meta information modification 2421 2021-07-13 04:07:41 |

Video Upload Options

Do you have a full video?
Send video materials Upload full video

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Sagris, M. Inflammatory Mechanisms in COVID-19, Atherosclerosis. Encyclopedia. Available online: https://encyclopedia.pub/entry/11945 (accessed on 25 April 2024).
Sagris M. Inflammatory Mechanisms in COVID-19, Atherosclerosis. Encyclopedia. Available at: https://encyclopedia.pub/entry/11945. Accessed April 25, 2024.
Sagris, Marios. "Inflammatory Mechanisms in COVID-19, Atherosclerosis" Encyclopedia, https://encyclopedia.pub/entry/11945 (accessed April 25, 2024).
Sagris, M. (2021, July 12). Inflammatory Mechanisms in COVID-19, Atherosclerosis. In Encyclopedia. https://encyclopedia.pub/entry/11945
Sagris, Marios. "Inflammatory Mechanisms in COVID-19, Atherosclerosis." Encyclopedia. Web. 12 July, 2021.
Inflammatory Mechanisms in COVID-19, Atherosclerosis
Edit
This entry is adapted from the peer-reviewed paper 10.3390/ijms22126607

Clinical studies have demonstrated that COVID-19 mortality is predominantly related to thromboembolic disease and coagulation abnormalities, in which the so-called “cytokine storm” and systemic inflammation play an orchestrating role. Inflammation plays an important pathogenic role in atherosclerotic cardiovascular disease in general and in ischemic heart disease in particular. Endothelial dysfunction, hyperinflammation, and coagulopathy contribute to disease severity and death in patients infected with SARS-CoV-2, while also being prevalent features of atherosclerosis. The presence of a cytokine storm in patients with COVID-19 causes ARDS or multiorgan dysfunction, including an increased risk of plaque rupture and direct myocardial injury (i.e., myocarditis), leading to high mortality rates. An optimal regulation of the cytokine storm in the early stages of the disease can contribute to treatment effectiveness and reduce the risk of cardiovascular complications, which are the leading cause of death in these patients. 

COVID-19 SARS-CoV-2 atherosclerosis inflammation

1. Inflammation in COVID-19

Coronaviruses (CoVs) are single-stranded RNA viruses that belong to the Coronaviridae family. The International Committee on Taxonomy of Viruses (ICTV) classifies the CoVs into four categories: α, β, γ, and δ. SARS-CoV-2 is the most recent coronavirus to infect humans. SARS-CoV, MERS-CoV, and SARS-CoV-2 are all viruses that cause extreme pneumonia. The SARS-CoV-2 genome is less than 30 kb in length and contains 14 open reading frames (ORFs) that encode non-structural proteins (NSPs) for viral replication and assembly processes; structural proteins such as spike (S), envelope (E), membrane/matrix (M), and nucleocapsid (N); and accessory proteins. COVID-19 is defined as an illness caused by the novel coronavirus. SARS-COV-2’s higher transmissibility, diverse clinical manifestations, and lower pathogenicity may be attributed to differences in biology and genome structure as compared to SARS-CoV and MERS-CoV.

SARS-CoV-2 enters human cells mainly by binding the angiotensin-converting enzyme 2 (ACE2), which is highly expressed by alveolar lung cells, vascular endothelium, cardiac myocytes, and other cells [1]. Patients suffering from cardiovascular or cerebrovascular comorbidities have a higher risk of infection and worse outcomes [2][3][4]. The virus spreads not only by inhalation of viral particles but also through contaminated surfaces, where it can live for 24–72 h depending on the type of surface. In most cases, the incubation time is shorter than 14 days, with the patient being contagious even though asymptomatic [1]. Commonly identified symptoms include fever, dry cough, dyspnea, chest pain, fatigue, and myalgia. Other less frequent symptoms are headache, dizziness, abdominal pain, diarrhea, nausea, and vomiting [5]. The virus decreases the Type-I Interferon (IFN) response and increases T cell apoptosis, as well as natural killers (NK) cell abnormalities. The direct attack and resulting immune system weakness may explain some of the extreme complications seen in COVID-19 patients, such as hypoxemia, ARDS, arrhythmias, trauma, acute myocardial injury, and acute kidney injury [6][1][7]. In the vast majority of COVID-19 patients, the typical chest computed tomography scan presents bilateral pulmonary parenchymal ground-glass and consolidative opacities, which is even worse in ICU-admitted patients with bilateral multiple lobular and subsegmental areas of consolidation [2][3][8][9]. Laboratory findings are not pathognomonic, with lymphopenia, prolonged prothrombin time, and elevated lactate dehydrogenase being the most prominent. Some patients with extreme bilateral pneumonia have elevated levels of aspartate aminotransferase, creatine kinase, creatinine, C-reactive protein (CRP), D-dimers, and ferritin [10].

2. The Cytokine Storm in COVID-19

The spectrum of symptoms ranges from asymptomatic infections to mild respiratory symptoms to the lethal form of COVID-19, which is associated with severe pneumonia, acute respiratory distress, and fatality. In the early stages of the disease, initial symptoms such as fever, cough, diarrhea, myalgia, or fatigue are present. COVID-19 patients may develop profound hypoxemia early in their disease course. However, overt respiratory failure at these early stages is unusual. Rarely, a minority of patients develop aggravating symptoms leading to multiorgan dysfunction and serious ARDS due to an intense inflammatory response and cytokine overproduction—the cytokine storm. Cytokines are small cell-signaling protein molecules, which may have autocrine or paracrine actions, facilitating intracellular crosstalk [11][12]. The cytokine family consists of more than 100 members, sub-categorized into several smaller clusters such as interleukins (ILs), INFs, colony-stimulating factors (CSFs), tumor necrosis factors (TNFs), and chemokines [13]. A cytokine storm resembling the hyperinflammatory state of COVID-19 has previously been recognized in several critically ill adults, namely those suffering from macrophage activation syndrome (MAS) or secondary hemophagocytic lymphohistiocytosis (sHLH). MAS/sHLH has historically been classified based on the cause of the disease and is categorized into primary (genetic) and secondary (non-genetic) types, and further subdivided into viral, autoimmune, or neoplasia-related [14]. The classic MAS/sHLH is characterized by fever, adenopathy, hepatosplenomegaly, anemia, other cytopenias, liver function abnormalities, and triggered hypercoagulation secondary to inflammation, followed by pronounced hypercytokinemia [7].

In immunodeficient patients with severe COVID-19 pneumonia, primary HLH may be the potential underlying cause. After entering respiratory epithelial cells, SARS-CoV-2 provokes the activation of Th1 cells to secrete pro-inflammatory cytokines. It is pictured by the failure of perforin, NK, and CD8+ cytotoxic T cells, which lead to cell lysis initiating apoptosis of virally infected cells. Additionally, IFN-γ, which is produced by a large number of widespread T cells, causes excessive macrophage activation [15]. In COVID-19 patients, the incidence of cardiovascular symptoms is high due to the systemic inflammatory response and immune system disorders during disease progression [16]. The exact mechanism of cardiac involvement in COVID-19 remains unclear. One potential mechanism is a direct myocardial involvement mediated via ACE2 or a direct viral effect on the heart muscle called myocarditis. Other proposed mechanisms of myocardial injury include cytokine activity and respiratory insufficiency, all of which may result in myocardial cell apoptosis through a gradual decrease in oxygen provided to the heart muscle [16]. In most immunocompetent patients with severe COVID-19 pneumonia, MAS/sHLH is suspected as the triggering cause of hyper-inflammation. The potential association between SARS-CoV-2 and sHLH relies on its key feature to bind Toll-like receptors (TLRs) and activate inflammasomes (caspases) releasing IL-1β [17]. In vitro cell studies indicate that in the early stages of SARS-CoV infection, respiratory epithelial cells, dendritic cells (DCs), and macrophages exhibit a delayed release of cytokines and chemokines [18]. The induction of low levels of antiviral factor IFNs and high levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF) as well as specific chemokines (C-C motif chemokine ligand (CCL)-2, CCL-3, and CCL-5) describe this hyperinflammatory state [19][20]. Therefore, the severity of COVID-19 has been strongly associated with the volume of hypercytokinemia, referring to interleukins IL-1β, IL-2, IL-6, IL-7, IL-10, TNF-alpha, granulocyte colony-stimulating factor (G-CSF), IFN-γ-induced protein 10 kDa/CXCL10, monocyte chemoattractant protein 1 (MCP-1), and macrophage inflammatory protein 1-α, both in serum and affected tissues [7][15]. After the secretion of the pro-inflammatory cytokines IL-1, IL-6, and G-CSF, low levels of IFN-αβ and IFN-γ induce inflammatory cell infiltration through mechanisms involving the Fas–Fas ligand (FasL) or the TRAIL–death receptor 5 (DR5) and trigger the apoptosis of airway and alveolar epithelial cells. Endothelial and epithelial cell apoptosis damages the pulmonary microvascular and alveolar epithelial cell barriers, resulting in vascular leakage, alveolar edema, and gradually, hypoxia [21][22]. Finally, the accumulated mononuclear macrophages engage in phagocytic activity on the debris of dead cells and tissues, secreting more pro-inflammatory cytokines (TNF, IL-6, IL-1β, and inducible nitric oxide synthase (NOS)) and chemoattractants (such as CCL-2, CCL-3, CCL-5, CCL-7, and IFN-γ-induced protein 10) [21]. The pro-inflammatory feed-forward loop of cytokines on innate immune cells results in a cytokine storm, coagulopathy, and acute respiratory distress syndrome [23] (Table 1).

Table 1. Cytokines involved in COVID-19 and their prognostic data.

IL-/TNF- and IFN-Family Cytokines
Factor Prognostic Value
IL-1β Elevated levels IL-1β have been associated with hypercoagulation, disseminated intravascular coagulation, and severe symptoms [24].
IL-2 Increases in IL-2 or its receptor IL-2R are directly proportional to the severity of the disease [8].
IL-4 IL-4 has negative effects on CD8+ memory T cells; elevated IL-4 levels are associated with cytokine storm and severe respiratory symptoms [25].
IL-6 Higher levels of IL-6 accelerates the inflammatory process, contributing to the cytokine storm and worsening the prognosis [14].
IL-12 NA
IL-17 Elevated IL-17 levels have been reported in patients with SARS-CoV-2 as part of the cytokine storm, and they are associated with viral load and disease severity [26].
IL-18 NA
IL-21 NA
IL-33 Higher IL-33 levels have been associated with lung fibrosis and skeletal muscle wasting [27].
TNF-alpha TNF-alpha was one of the cytokines whose overproduction was related to a poor prognosis in patients with SARS-CoV-2, finding an inverse relationship between TNF-alpha levels and T cell counts [28].
TGF-β NA
IFN-α NA
IFN-γ IFN-γ levels are associated with greater viral load and lung damage [29].
Chemokines
CCL2/MCP-1 CCL2 levels were higher in patients with COVID-19 and even higher among those admitted to the Intensive Care Unit [3].
CCL3/MIP-1A NA
CCL5 NA
CXCL9 NA
CXCL10/IP-10 IP-10 levels were found to be elevated in patients with COVID-19 and even higher in those who required Intensive Care Unit admission, suggesting their relationship with lung damage and disease severity [3].

IL- = Interleukin, TNF-alpha = Tumor Necrosis Factor-alpha, TGF-β = Transforming Growth Factor-β, IFN- = Interferon, CCL = C-C Motif Chemokine Ligand, CXCL = C-X-C Motif Chemokine Ligand, MCP-1 = Monocyte chemoattractant protein-1, MIP-1A = Macrophage inflammatory protein-1A, IP-10 = Interferon gamma-induced protein 10.

3. Inflammation and Pro-Inflammatory Cytokines in Atherosclerosis

Atherosclerosis is characterized by the formation of plaques in the vessel wall. These develop through complex pathophysiological pathways that involve pro- and anti-inflammatory cytokines, secreted by vascular endothelial cells, leukocytes, platelets, and mast cells [13][11]. Endothelial injury, impaired lipid metabolism, and hemodynamic disruption, followed by flow-mediated inflammatory changes in the endothelium, are the main steps in plaque formation and atherosclerosis progression [2]. Inflammation begins when the endothelial cells become activated and secrete adhesion molecules (intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), E-selectin, and P-selectin) and other inflammatory factors while the smooth muscle cells secrete chemokines and chemoattractants (monocyte chemoattractant protein-1 (MCP-1)), which jointly draw monocytes, lymphocytes, mast cells, and neutrophils into the arterial wall, followed by their migration to the sub-endothelial space [13][30]. The effect of two pro-inflammatory cytokines, TNF-alpha and IL-1, which promote the expression of cytokines, adhesion molecules as well as the migration and mitogenesis of vascular smooth muscle and endothelial cells, is of particular interest [31]. TNF-alpha and IFN-γ have also been associated with the disruption of endothelial cell junctions, leading to leukocyte transmigration, vascular permeability, and matrix degradation, all of which facilitate atherosclerosis development [13][30][31][32].

With regards to human monocytes, three subsets exist owing to differences in functions [33]. CD14+CD16++ monocytes, similar to murine lymphocyte antigen 6 complex (Ly6C) low monocytes, patrol the vasculature and are involved in the early inflammatory response, while CD14+CD16+ monocytes exert both phagocytic and anti-inflammatory actions. Classical CD14++CD16− monocytes, which are similar to murine Ly6C high monocytes, differentiate to macrophages and engulf a large number of chemically modified (by reactive oxygen species) low-density lipoprotein (LDL) particles known as oxidized LDL (oxLDL), which are prone to phagocytosis [13][34]. The accumulation of oxLDL in the macrophages transforms them into foam cells, contributing in this way to atherosclerotic plaques [35]. T cells, B cells, neutrophils, dendritic cells, and myeloid cell proliferation are types of resistant chemoattracted cells found in atherosclerotic lesions [36].

Selectins and platelet endothelial cell adhesion molecule (PECAM-1) assist the accumulation of leukocytes into the sub-endothelial space, inducing the inflammation and volume of the lipid core [37]. Fibrous tissue is added to form a fibrous cap over the lipid-rich necrotic cores and just under the endothelium at the blood interface. With aging, the persistent unregulated action of proteolytic enzymes dissolves the fibrous tissue; the fibrous cap becomes thinner and weakens. This thin cap is prone to rupture, exposing the thrombogenic material of the internal arterial wall leading to thrombus formation. As far as the vulnerability of plaque is concerned, studies have focused on the collagenolytic action of matrix metalloproteinases and cysteine proteases in the plaque [38]. The expression of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) increases the risk of plaque rupture, bleeding, and thrombosis [39][40]. Recent studies have shown that IL-1, as well as TNF-alpha and its superfamily of CD40/CD40L ligand, disrupt the fibrinolytic and anti-thrombotic actions triggering thrombotic events [41]. It has also been described that in later stages of atherosclerosis, cytokines such as TNF-alpha, INF-γ, IL-1, and IL-6 act differently, inducing smooth muscle cell apoptosis and matrix degradation, leading to plaque destabilization [42][43]. Similar effects have been noted following the increase of acute-phase proteins, the proliferation of foam cells, and the reduced secretion of NO. CRP has also been linked to a pro-thrombotic function, as it is associated with TF upregulation, decreased levels of prostaglandins (PGI2) and endothelial NOS, and the impairment of coagulation balance, as measured by the thromboxane A2/PGI2 ratio [44][45][46][47]. Finally, the triple activity of INF-γ has been found to destabilize the plaque (as it prevents smooth muscle differentiation), the procollagen-I gene expression, and the collagen crosslinking enzyme, lysyl oxidase [48][49][50].

4. Similarities in the Inflammatory Processes Operating in COVID-19 and Atherosclerosis

COVID-19 presents not only complications in the venous and arterial circulations, but also multiorgan dysfunction [18]. This excessive response has a lot in common with the systemic low-grade inflammation in atherosclerosis. Initially, the impaired vessel endothelium following exposure to cytokines leads to decreased vasodilation in both atherosclerosis and COVID-19, as there is a reduction in the secretion of NO in both situations. Moreover, an improper activation of the coagulation cascade has been observed in COVID-19 patients [51]. Coagulation activation and endothelial dysfunction could be the expression of the sustained inflammatory response associated with vascular inflammation. Interestingly, this endothelium-related prothrombotic state is more prevalent in the lungs than in the lower limbs, even lacking particular risk factors and a history of thromboembolism [51]. The American Heart Association (AHA) suggests that viral infection reduces the cohesion of atherosclerotic plaque and encourages the progression of atherosclerosis and coronary heart disease [51]. IL-1β and IL-6 have major roles in both diseases. IL-6 may be significantly elevated in patients with ARDS from SARS-CoV-2, inducing the secretion of acute phase reactants, although the magnitude of cytokine level is not specific for the disease [52]. Studies showed that the higher circulating cytokine levels are, the more severe manifestations of COVID-19 pneumonia are seen [52]. In the same way, IL-18 and IL-12 in combination with IL-1β induce IFN-γ secretion and promote Th cell and NK activity in both atherosclerosis and COVID-19 [53][54]. Additionally, there are similarities in the secretion of IFN-α, IFN-γ, and TGF-β, as well that of TNF-alpha [7]. It is hypothesized that the atherogenic cytokines found in the plasma of COVID-19 patients are regulated by the shedding of ACE2, the portal allowing SARS-CoV-2 cell entry, or after virus incursion intracellularly [7]. Finally, in COVID-19, the apoptosis of endothelial and epithelial cells in the pulmonary microvasculature and tissues causes the release of chemokines, mainly from the CXC family CXCL9 and CXCL10, MCP-1 (CCL2), CCL2, and CCL3, which can be found in atherosclerotic plaque formation, leading to monocyte/lymphocyte recruitment and infiltration into the subendothelium [19][55][56].

References

  1. Chang, D.; Lin, M.; Wei, L.; Xie, L.; Zhu, G.; Cruz, C.S.D.; Sharma, L. Epidemiologic and Clinical Characteristics of Novel Coronavirus Infections Involving 13 Patients Outside Wuhan, China. JAMA 2020, 323, 1092–1093.
  2. Huang, C.; Wang, Y.; Li, X.; Ren, L.; Zhao, J.; Zhang, L.; Fan, G.; Xu, J.; Gu, X.; Cheng, Z.; et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020, 395, 497–506.
  3. Wang, D.; Hu, B.; Hu, C.; Zhu, F.; Liu, X.; Zhang, J.; Wang, B.; Xiang, H.; Cheng, Z.; Xiong, Y.; et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA 2020, 323, 1061–1069.
  4. Bai, Y.; Yao, L.; Wei, T.; Tian, F.; Jin, D.Y.; Chen, L.; Wang, M. Presumed Asymptomatic Carrier Transmission of COVID-19. JAMA 2020, 323, 1406–1407.
  5. Ye, Q.; Wang, B.; Mao, J. The pathogenesis and treatment of the Cytokine Storm in COVID-19. J. Infect. 2020, 80, 607–613.
  6. Sterne, J.A.C. Association between Administration of Systemic Corticosteroids and Mortality among Critically Ill Patients With COVID-19: A Meta-analysis. JAMA 2020, 324, 1330–1341.
  7. Chen, G.; Wu, D.; Guo, W.; Cao, Y.; Huang, D.; Wang, H.; Wang, T.; Zhang, X.; Chen, H.; Yu, H.; et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J. Clin. Investig. 2020, 130, 2620–2629.
  8. Lei, J.; Li, J.; Li, X.; Qi, X. CT Imaging of the 2019 Novel Coronavirus (2019-nCoV) Pneumonia. Radiology 2020, 295, 18.
  9. Chan, J.F.W.; Yuan, S.; Kok, K.H.; To, K.K.W.; Chu, H.; Yang, J.; Xing, F.; Liu, J.; Yip, C.C.Y.; Poon, R.W.S.; et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: A study of a family cluster. Lancet 2020, 395, 514–523.
  10. Schaftenaar, F.; Frodermann, V.; Kuiper, J.; Lutgens, E. Atherosclerosis: The interplay between lipids and immune cells. Curr. Opin. Lipidol. 2016, 27, 209–215.
  11. Brott, T.G.; Hobson, R.W.; Howard, G.; Roubin, G.S.; Clark, W.M.; Brooks, W.; Mackey, A.; Hill, M.D.; Leimgruber, P.P.; Sheffet, A.J.; et al. Stenting versus endarterectomy for treatment of carotid-artery stenosis. N. Engl. J. Med. 2010, 363, 11–23.
  12. Mehta, P.; McAuley, D.F.; Brown, M.; Sanchez, E.; Tattersall, R.S.; Manson, J.J. COVID-19: Consider cytokine storm syndromes and immunosuppression. Lancet 2020, 395, 1033–1034.
  13. Bikdeli, B.; Madhavan, M.V.; Jimenez, D.; Chuich, T.; Dreyfus, I.; Driggin, E.; Der Nigoghossian, C.; Ageno, W.; Madjid, M.; Guo, Y.; et al. COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-up: JACC state-of-the-art review. J. Am. Coll. Cardiol. 2020, 75, 2950–2973.
  14. Alunno, A.; Carubbi, F.; Rodríguez-Carrio, J. Storm, typhoon, cyclone or hurricane in patients with COVID-19? Beware of the same storm that has a different origin. RMD Open 2020, 6, e001295.
  15. Li, G.; Hu, R.; Gu, X. A close-up on COVID-19 and cardiovascular diseases. Nutr. Metab. Cardiovasc. Dis. 2020, 30, 1057–1060.
  16. Conti, P.; Ronconi, G.; Caraffa, A.L.; Gallenga, C.E.; Ross, R.; Frydas, I.; Kritas, S.K. Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): Anti-inflammatory strategies. J. Biol. Regul. Homeost. Agents 2020, 34, 1.
  17. Cheung, C.Y.; Poon, L.L.M.; Ng, I.H.Y.; Luk, W.; Sia, S.-F.; Wu, M.H.S.; Chan, K.-H.; Yuen, K.-Y.; Gordon, S.; Guan, Y.; et al. Cytokine responses in severe acute respiratory syndrome coronavirus-infected macrophages in vitro: Possible relevance to pathogenesis. J. Virol. 2005, 79, 7819–7826.
  18. Lau, S.K.P.; Lau, C.C.Y.; Chan, K.-H.; Li, C.P.Y.; Chen, H.; Jin, D.-Y.; Chan, J.F.W.; Woo, P.C.Y.; Yuen, K.-Y. Delayed induction of proinflammatory cytokines and suppression of innate antiviral response by the novel Middle East respiratory syndrome coronavirus: Implications for pathogenesis and treatment. J. Gen. Virol. 2013, 94, 2679–2690.
  19. Law, H.K.-W.; Cheung, C.Y.; Ng, H.Y.; Sia, S.F.; Chan, Y.O.; Luk, W.; Nicholls, J.M.; Peiris, J.S.M.; Lau, Y.L. Chemokine up-regulation in SARS-coronavirus-infected, monocyte-derived human dendritic cells. Blood 2005, 106, 2366–2374.
  20. Hogner, K.; Wolff, T.; Pleschka, S.; Plog, S.; Gruber, A.D.; Kalinke, U.; Herold, S.; Walmrath, H.-D.; Bodner, J.; Gattenlohner, S.; et al. Correction: Macrophage-expressed IFN-beta Contributes to Apoptotic Alveolar Epithelial Cell Injury in Severe Influenza Virus Pneumonia. PLoS Pathog. 2016, 12, e1005716.
  21. Rodrigue-Gervais, I.G.; Labbé, K.; Dagenais, M.; Dupaul-Chicoine, J.; Champagne, C.; Morizot, A.; Skeldon, A.; Brincks, E.L.; Vidal, S.M.; Griffith, T.S.; et al. Cellular inhibitor of apoptosis protein cIAP2 protects against pulmonary tissue necrosis during influenza virus infection to promote host survival. Cell Host Microbe 2014, 15, 23–35.
  22. Henderson, L.A.; Canna, S.W.; Schulert, G.S.; Volpi, S.; Lee, P.Y.; Kernan, K.F.; Caricchio, R.; Mahmud, S.; Hazen, M.M.; Halyabar, O.; et al. On the Alert for Cytokine Storm: Immunopathology in COVID-19. Arthritis. Rheumatol. 2020, 72, 1059–1063.
  23. Zhang, W.; Zhao, Y.; Zhang, F.; Wang, Q.; Li, T.; Liu, Z.; Wang, J.; Qin, Y.; Zhang, X.; Yan, X.; et al. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China. Clin. Immunol. 2020, 214, 108393.
  24. Bot, A.; Holz, A.; Christen, U.; Wolfe, T.; Temann, A.; Flavell, R.; von Herrath, M. Local IL-4 expression in the lung reduces pulmonary influenza-virus-specific secondary cytotoxic T cell responses. Virology 2000, 269, 66–77.
  25. Zeng, H.L.; Chen, D.; Yan, J.; Yang, Q.; Han, Q.; Li, S.; Cheng, L. Proteomic characteristics of bronchoalveolar lavage fluid in critical COVID-19 patients. FEBS J. 2020.
  26. Shieh, J.M.; Tseng, H.-Y.; Jung, F.; Yang, S.-H.; Lin, J.-C. Elevation of IL-6 and IL-33 Levels in Serum Associated with Lung Fibrosis and Skeletal Muscle Wasting in a Bleomycin-Induced Lung Injury Mouse Model. Mediat. Inflamm. 2019, 2019, 7947596.
  27. Mahallawi, W.H.; Khabour, O.F.; Zhang, Q.; Makhdoum, H.M.; Suliman, B.A. MERS-CoV infection in humans is associated with a pro-inflammatory Th1 and Th17 cytokine profile. Cytokine 2018, 104, 8–13.
  28. Lee, J.S.; Park, S.; Jeong, H.W.; Ahn, J.Y.; Choi, S.J.; Lee, H.; Choi, B.; Nam, S.K.; Sa, M.; Kwon, J.-S.; et al. Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19. Sci. Immunol. 2020, 5, eabd1554.
  29. Tedgui, A.; Mallat, Z. Cytokines in atherosclerosis: Pathogenic and regulatory pathways. Physiol. Rev. 2006, 86, 515–581.
  30. Chan, K.F.; Siegel, M.R.; Lenardo, J.M. Signaling by the TNF receptor superfamily and T cell homeostasis. Immunity 2000, 13, 419–422.
  31. Pena, E.; De La Torre, R.; Arderiu, G.; Slevin, M.; Badimon, L. mCRP triggers angiogenesis by inducing F3 transcription and TF signalling in microvascular endothelial cells. Thromb. Haemost. 2017, 117, 357–370.
  32. Kratofil, R.M.; Kubes, P.; Deniset, J.F. Monocyte Conversion during Inflammation and Injury. Arterioscler. Thromb. Vasc. Biol. 2017, 37, 35–42.
  33. Swirski, F.K.; Nahrendorf, M.; Libby, P. Mechanisms of Myeloid Cell Modulation of Atherosclerosis. Microbiol. Spectr. 2016, 4, 813–824.
  34. Pirillo, A.; Norata, G.D.; Catapano, A.L. LOX-1, OxLDL, and atherosclerosis. Mediat. Inflamm. 2013, 2013, 152786.
  35. Rosenfeld, M.E.; Ross, R. Macrophage and smooth muscle cell proliferation in atherosclerotic lesions of WHHL and comparably hypercholesterolemic fat-fed rabbits. Arteriosclerosis 1990, 10, 680–687.
  36. Kaartinen, M.; Penttila, A.; Kovanen, P.T. Mast cells of two types differing in neutral protease composition in the human aortic intima. Demonstration of tryptase- and tryptase/chymase-containing mast cells in normal intimas, fatty streaks, and the shoulder region of atheromas. Arter. Thromb. 1994, 14, 966–972.
  37. Henney, A.M.; Wakeley, P.R.; Davies, M.J.; Foster, K.; Hembry, R.; Murphy, G.; Humphries, S. Localization of stromelysin gene expression in atherosclerotic plaques by in situ hybridization. Proc. Natl. Acad. Sci. USA 1991, 88, 8154–8158.
  38. Libby, P. Current concepts of the pathogenesis of the acute coronary syndromes. Circulation 2001, 104, 365–372.
  39. Liu, Y.; Yu, H.; Zhang, Y.; Zhao, Y. TLRs are important inflammatory factors in atherosclerosis and may be a therapeutic target. Med. Hypotheses 2008, 70, 314–316.
  40. Antoniades, C.; Bakogiannis, C.; Tousoulis, D.; Antonopoulos, A.S.; Stefanadis, C. The CD40/CD40 ligand system: Linking inflammation with atherothrombosis. J. Am. Coll. Cardiol. 2009, 54, 669–677.
  41. Pepys, M.B.; Hirschfield, G.M. C-reactive protein: A critical update. J. Clin. Invest. 2003, 111, 1805–1812.
  42. Lane, T.; Wassef, N.; Poole, S.; Mistry, Y.; Lachmann, H.J.; Gillmore, J.D.; Hawkins, P.N.; Pepys, M.B. Infusion of pharmaceutical-grade natural human C-reactive protein is not proinflammatory in healthy adult human volunteers. Circ. Res. 2014, 114, 672–676.
  43. Venugopal, S.K.; Devaraj, S.; Jialal, I. C-reactive protein decreases prostacyclin release from human aortic endothelial cells. Circulation 2003, 108, 1676–1678.
  44. Verma, S.; Wang, C.H.; Li, S.H.; Dumont, A.S.; Fedak, P.W.; Badiwala, M.V.; Stewart, D.J.; Dhillon, B.; Weisel, R.D.; Li, R.-K.; et al. A self-fulfilling prophecy: C-reactive protein attenuates nitric oxide production and inhibits angiogenesis. Circulation 2002, 106, 913–919.
  45. Venugopal, S.K.; Devaraj, S.; Yuhanna, I.; Shaul, P.; Jialal, I. Demonstration that C-reactive protein decreases eNOS expression and bioactivity in human aortic endothelial cells. Circulation 2002, 106, 1439–1441.
  46. Cermak, J.; Key, N.S.; Bach, R.R.; Balla, J.; Jacob, H.S.; Vercellotti, G.M. C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor. Blood 1993, 82, 513–520.
  47. Amento, E.P.; Ehsani, N.; Palmer, H.; Libby, P. Cytokines and growth factors positively and negatively regulate interstitial collagen gene expression in human vascular smooth muscle cells. Arter. Thromb. 1991, 11, 1223–1230.
  48. Hansson, G.K.; Hellstrand, M.; Rymo, L.; Rubbia, L.; Gabbiani, G. Interferon gamma inhibits both proliferation and expression of differentiation-specific alpha-smooth muscle actin in arterial smooth muscle cells. J. Exp. Med. 1989, 170, 1595–1608.
  49. Ovchinnikova, O.; Robertson, A.K.L.; Wågsäter, D.; Folco, E.J.; Hyry, M.; Myllyharju, J.; Eriksson, P.; Libby, P.; Hansson, G.K. T-cell activation leads to reduced collagen maturation in atherosclerotic plaques of Apoe(-/-) mice. Am. J. Pathol. 2009, 174, 693–700.
  50. Srivastava, K. Association between COVID-19 and cardiovascular disease. Int. J. Cardiol. Heart Vasc. 2020, 29, 100583.
  51. Min, C.K.; Cheon, S.; Ha, N.Y.; Sohn, K.M.; Kim, Y.; Aigerim, A.; Kim, Y.S.; Shin, H.-M.; Choi, J.-Y.; Inn, K.-S.; et al. Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity. Sci. Rep. 2016, 6, 25359.
  52. Mallat, Z.; Heymes, C.; Corbaz, A.; Logeart, D.; Alouani, S.; Cohen-Solal, A.; Seidler, T.; Hasenfuss, G.; Chvatchko, Y.; Shah, A.M.; et al. Evidence for altered interleukin 18 (IL)-18 pathway in human heart failure. FASEB J. 2004, 18, 1752–1754.
  53. Shimabukuro-Vornhagen, A.; Gödel, P.; Subklewe, M.; Stemmler, H.J.; Schlößer, H.A.; Schlaak, M.; Kochanek, M.; Böll, B.; Von Bergwelt-Baildon, M.S. Cytokine release syndrome. J. Immunother. Cancer 2018, 6, 56.
  54. Lapidot, T.; Petit, I. Current understanding of stem cell mobilization: The roles of chemokines, proteolytic enzymes, adhesion molecules, cytokines, and stromal cells. Exp. Hematol. 2002, 30, 973–981.
  55. Weber, C.; Schober, A.; Zernecke, A. Chemokines: Key regulators of mononuclear cell recruitment in atherosclerotic vascular disease. Arter. Thromb. Vasc. Biol. 2004, 24, 1997–2008.
  56. Bansal, M. Cardiovascular disease and COVID-19. Diabetes Metab. Syndr. 2020, 14, 247–250.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Medicine, Research & Experimental
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Marios Sagris
View Times: 369
Revisions: 2 times (View History)
Update Date: 13 Jul 2021
Table of Contents
    1000/1000
    Hot Most Recent
    Feedback