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 -- 1394 2023-04-20 03:35:51 |
2 format correct + 16 word(s) 1410 2023-04-20 06:52:09 | |
3 format correct -2 word(s) 1408 2023-04-24 09:49:08 |

Video Upload Options

Do you have a full video?


Are you sure to Delete?
If you have any further questions, please contact Encyclopedia Editorial Office.
Jia, Z.; Wang, S.; Yan, H.; Cao, Y.; Zhang, X.; Wang, L.; Zhang, Z.; Lin, S.; Wang, X.; Mao, J. Intima Remodeling in Pulmonary Vascular Remodeling. Encyclopedia. Available online: (accessed on 30 May 2024).
Jia Z, Wang S, Yan H, Cao Y, Zhang X, Wang L, et al. Intima Remodeling in Pulmonary Vascular Remodeling. Encyclopedia. Available at: Accessed May 30, 2024.
Jia, Zhuangzhuang, Shuai Wang, Haifeng Yan, Yawen Cao, Xuan Zhang, Lin Wang, Zeyu Zhang, Shanshan Lin, Xianliang Wang, Jingyuan Mao. "Intima Remodeling in Pulmonary Vascular Remodeling" Encyclopedia, (accessed May 30, 2024).
Jia, Z., Wang, S., Yan, H., Cao, Y., Zhang, X., Wang, L., Zhang, Z., Lin, S., Wang, X., & Mao, J. (2023, April 20). Intima Remodeling in Pulmonary Vascular Remodeling. In Encyclopedia.
Jia, Zhuangzhuang, et al. "Intima Remodeling in Pulmonary Vascular Remodeling." Encyclopedia. Web. 20 April, 2023.
Intima Remodeling in Pulmonary Vascular Remodeling

Pulmonary vascular remodeling is the critical structural alteration and pathological feature in pulmonary hypertension (PH) and involves changes in the intima, media and adventitia. Pulmonary vascular remodeling consists of the proliferation and phenotypic transformation of pulmonary artery endothelial cells (PAECs) and pulmonary artery smooth muscle cells (PASMCs) of the middle membranous pulmonary artery, as well as complex interactions involving external layer pulmonary artery fibroblasts (PAFs) and extracellular matrix (ECM). Inflammatory mechanisms,apoptosis and other factors in the vascular wall are influenced by different mechanisms that likely act in concert to drive disease progression. These pathological changes and some pathogenetic mechanisms involved in the remodeling process are described.

pulmonary hypertension pulmonary vascular remodeling

1. Introduction

The intima represents the thick interface of endothelial cells between the media and flowing blood. The endothelial cells provide a broad unobstructed flow surface area, contributing to the suitable perfusion pressure that is the normal state of pulmonary circulation [1]. Patients with severe pulmonary hypertension (PH) have an approximately 3 fold increase in pulmonary intima, but the mechanism of intima damage is unclear [2] and intimal thickening will result in an approximately 40-fold increase in resistance of the pulmonary vascular. There are various types of intimal thickening and pulmonary artery endothelial cells (PAECs) dysfunction, as the most critical component of the intima accelerates the process of intima remodeling [3]. Under normal physiological conditions, PAECs are in a steady state and secrete a variety of active factors that disturb PAECs and PASMCs proliferation, coagulation, the attraction of inflammatory factors and activation of vasoactivity, which leads to dysfunction and pathological changes of PASMCs in PH [4]. Multiple factors trigger PAECs dysfunction in PH [5][6][7][8], such as shear stress, hypoxia, inflammation, PAECs phenotypes, the bone morphogenic type 2 receptor (BMPR2), and cilia length [9][10][11] (Figure 1). Meanwhile, the deterioration of endothelial metabolic function in the pulmonary vascular system is becoming an important driver of PAECs dysfunction and PH development [12].
Figure 1. Pathogenesis of pulmonary vascular intima remodeling in PH. In response to hypoxia, shear stress, inflammation, and genetic predisposition, the function and phenotype of PACEs are altered, resulting in intima remodeling in PH.

2. Phenotypes of Pulmonary Artery Endothelial Cells Dysfunction in Intima Remodeling

Damage and apoptosis of PAECs can occur in the early stages of PH pathogenesis, while anti-apoptotic PAECs appear later as PH progresses [13]. In late PH, hyperproliferative and anti-apoptotic PAECs predominate and facilitate the formation of plexiform lesions [14]. The pathogenesis of PH is usually associated with abnormal endothelial cell barrier integrity, and patients with idiopathic PH (iPH) often exhibit a hypercoagulable phenotype. Additionally, there is a growing awareness that complex alterations in metabolic and epigenetic pathways facilitate the progression of PH [8]. However, it is essential to note here that PAECs include separate subpopulations of endothelial cells, which are possible exposure to multiple adverse stimuli and physical damages depending on location in the pulmonary vascular system [15].
Endothelial-mesenchymal transition (EndoMT) is a phenotypic change in which PAECs manifest a mesenchymal-like phenotype with concomitant endothelial cell characteristics loss while upregulating the level of mesenchymal markers. Furthermore, PAECs adopt highly migratory and invasive cell phenotype characteristics with loss of cell-cell contact [16]. Strongly expressed α-smooth muscle actin (α-SMA), vimentin and VE-cadherin appeared in the PAECs of human PH patients and PH rat models induced by monocrotaline (MCT) hypoxia accompanied EndoMT. PAECs treated with transforming growth factor beta (TGF-β) induce the levels of the EndoMT transcription factors TWIST1, SNAIL1 and the previously mentioned mesenchymal markers involved in this process [17][18]. More interestingly, BMP-7 was abrogated in hypoxia-induced PAECs by the action of EndoMT via inhibiting the mTORC1 signaling pathway [19]. Low BMPR2 expression favors EndoMT leading to over-activated TGF-β signaling [20]. In conclusion, altered TGF-β/BMP signaling is associated with the EndoMT process in PH [21]. Hypoxia acts as an inducer of EndoMT via increasing hypoxia-inducible transcription factor-1α (HIF-1α) and hypoxia-inducible transcription factor-2α (HIF-2α) in PH [22]. Finally, microRNA, such as miR-27a, miR-124 and miR-181b, can be implicated in EndoMT in PH [23][24][25] (Figure 2).
Figure 2. EndoMT of PACEs in pulmonary vascular intima remodeling. EndoMT is a phenotypic change in which PAECs manifesting a mesenchymal-like phenotype with concomitant endothelial cell characteristics loss while upregulating the level of mesenchymal markers. Furthermore, PAECs adopt highly migratory and invasive cell phenotype characteristics with losing cell-cell contact. The EndoMT process is regulated by the mTOR, TGF-β, BMP and HIF signaling pathway. microRNA, such as miR-27a, miR-124 and miR-181b can be implicated in EndoMT in PH.

3. Pulmonary Artery Endothelial Cells Survival and Proliferation in Intima Remodeling

BMP receptor signaling, which is encoded by SMAD1, SMAD4 and SMAD9, plays an important role in PH development. BMPR2, as a transmembrane enzyme receptor that regulates TGF-β signaling in PAECs in the lumen of the pulmonary vessels, promotes the survival of PAECs and antagonizes PASMCs proliferation [26][27]. Interestingly, GDF2 encodes the circulating BMP 9, which is a ligand for the BMP2 receptor, and mutations in GDF2 reduced levels of BMP family expression [28].
Additionally, siRNA-mediated silencing of BMPR2 in PAECs contributes to the inhibition of Ras/Raf/ERK and Ras signaling reversing proliferation and hypermotility [29]. With the further development of pathology in PH, PAECs proliferation is a major manifestation resulting in complex arterial structural and functional remodeling, and multiple pathways regulate this transition. Peroxisome proliferator-activated receptor-γ in PAECs inhibits the cell cycle and disrupts endothelial cell barrier function, while antagonizing the migration and angiogenic properties of PAECs [30]. Furthermore, recent studies have suggested a role for endothelial prolyl hydroxylase 2 (PHD2) in PH pathology, and mice with Tie2Core-mediated PHD2 disruption in PAECs exhibited vascular remodeling in PH [31].
The proliferation and survival of PAECs are influenced by several other factors that also exacerbate the pathological condition of PH, such as disruption of Cav1 [32]. mTOR, Nur77 and GDF11 also act as inhibitors of PAECs proliferation and angiogenesis after hypoxia [33][34]. Oxidative, antioxidant and nitrification equally affect endothelial function. Inhibition of reactive oxygen species (ROS)-induced Ca2+ entry also downregulates the migration and proliferation of PAECs [35]. It has been recently shown that endostatin, a cleavage product of Col18A1, inhibits PAECs proliferation and apoptosis via CD47 and ID1/TSP-1/CD36 signaling [36]. The absence of Notch coupling to Sox17 in endothelial cells may exacerbate PH by upregulating the monolayer vulnerability of PAECs [37]. These findings demonstrate the complex relationship between PAECs survival and proliferation in PH.

4. Pulmonary Artery Endothelial Cells Activation and Thrombogenicity in Intima Remodeling

The presence of thrombotic lesions is a common pathological manifestation of PH. However, the role assumed by thrombus in PH remains controversial [38]. Multiple factors participate in the regulation of PH by affecting PAECs activation and thrombogenicity. A few studies have shown that coagulation factors, represented by activators of the coagulation cascade, lead to the aggregation of fibrin clots and blockage of blood vessels and exacerbate PAECs dysfunction, leading to vascular remodeling [39]. The levels of von Willebrand Factor (vWF) in PH patients also increase in the plasma. PAECs and platelets express and release vWF when activated, facilitating their interaction. The levels of thrombomodulin, as a series of anti-coagulant factors, are decreased in PH patients, which can inhibit this deterioration by ingesting prostacyclin, vasodilators or tadalafil [40]. CD40L is an inflammatory factor that cleaves into sCD40L upon activation, which is known to promote significantly in PH patients, eventually contributing to vascular remodeling in PH [41]. Although substantial evidence suggests that platelets and thrombogenicity exacerbate the pathogenesis of PAECs dysfunction, the molecular mechanisms need further elucidation.

5. Pulmonary Artery Endothelial Cells Metabolism and Epigenetics in Intima Remodeling

Factors affecting PAECs metabolism and epigenetics participate in the regulation of PH. Metabolic abnormalities, particularly aerobic glycolysis or the Warburg effect, have been proposed as important pathogenic mechanisms in developing PH. PFKFB3 is an essential regulator of glycolysis, and its deficiency inhibits pulmonary vascular remodeling [42]. Endothelin 1/eNOS signaling also serves as an essential pathway that regulates the glycolytic process [43]. Further studies suggest that BolA family member 3 (BOLA3) is involved in the operation of glycolysis and mitochondrial respiratory function [44]. Epigenetic mechanisms are also generally considered to be important in regulating PAECs metabolism. The delivery of glutamine carbon into the tricarboxylic acid (TCA) cycle becomes active in PAECs in the case of mutations in the BMPR2 gene, and the strict requirement for glutamine is driven by the loss of deacetylase sirtuin 3 activities. Additionally, the pharmacological effects of glutaminase can be targeted to reduce the severity of PH pathology [45]. The distribution of other genetic variants showed that variants in ACVRL1, ENG, SMAD9, KCNK3 and TBX4 contributed to PH [46], but only about 1% of the cases in each gene. Therefore, these factors are emerging as promising targets for PH treatment.


  1. Tuder, R.M. Pulmonary vascular remodeling in pulmonary hypertension. Cell Tissue Res. 2017, 367, 643–649.
  2. Stacher, E.; Graham, B.B.; Hunt, J.M.; Gandjeva, A.; Groshong, S.D.; McLaughlin, V.V.; Jessup, M.; Grizzle, W.E.; Aldred, M.A.; Cool, C.D.; et al. Modern age pathology of pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med. 2012, 186, 261–272.
  3. Evans, C.E.; Cober, N.D.; Dai, Z.; Stewart, D.J. Endothelial cells in the pathogenesis of pulmonary arterial hypertension. Eur. Respir. J. 2021, 58, 2003957.
  4. Nie, X.; Shen, C.; Tan, J.; Wu, Z.; Wang, W.; Chen, Y.; Dai, Y.; Yang, X.; Ye, S.; Chen, J.; et al. Periostin: A Potential Therapeutic Target For Pulmonary Hypertension? Circ. Res. 2020, 127, 1138–1152.
  5. Dummer, A.; Rol, N.; Szulcek, R.; Kurakula, K.; Pan, X.; Visser, B.I.; Bogaard, H.J.; DeRuiter, M.C.; Goumans, M.J.; Hierck, B.P. Endothelial dysfunction in pulmonary arterial hypertension: Loss of cilia length regulation upon cytokine stimulation. Pulm. Circ. 2018, 8, 2045894018764629.
  6. Gorelova, A.; Berman, M.; Al Ghouleh, I. Endothelial-to-Mesenchymal Transition in Pulmonary Arterial Hypertension. Antioxid. Redox Signal. 2021, 34, 891–914.
  7. Rodor, J.; Chen, S.H.; Scanlon, J.P.; Monteiro, J.P. Single-cell RNA sequencing profiling of mouse endothelial cells in response to pulmonary arterial hypertension. Cardiovasc. Res. 2022, 118, 2519–2534.
  8. Ranchoux, B.; Harvey, L.D.; Ayon, R.J.; Babicheva, A.; Bonnet, S.; Chan, S.Y.; Yuan, J.X.; Perez, V.J. Endothelial dysfunction in pulmonary arterial hypertension: An evolving landscape (2017 Grover Conference Series). Pulm. Circ. 2018, 8, 2045893217752912.
  9. Bochenek, M.L.; Rosinus, N.S.; Lankeit, M.; Hobohm, L.; Bremmer, F.; Schütz, E.; Klok, F.A.; Horke, S.; Wiedenroth, C.B.; Münzel, T.; et al. From thrombosis to fibrosis in chronic thromboembolic pulmonary hypertension. Thromb. Haemost. 2017, 117, 769–783.
  10. Chabert, C.; Khochbin, S.; Rousseaux, S.; Veyrenc, S. Inhibition of BET Proteins Reduces Right Ventricle Hypertrophy and Pulmonary Hypertension Resulting from Combined Hypoxia and Pulmonary Inflammation. Int. J. Mol. Sci. 2018, 19, 2224.
  11. Hautefort, A.; Mendes-Ferreira, P.; Sabourin, J.; Manaud, G.; Bertero, T.; Rucker-Martin, C.; Riou, M.; Adão, R.; Manoury, B.; Lambert, M.; et al. Bmpr2 Mutant Rats Develop Pulmonary and Cardiac Characteristics of Pulmonary Arterial Hypertension. Circulation 2019, 139, 932–948.
  12. Morrell, N.W.; Aldred, M.A.; Chung, W.K.; Elliott, C.G.; Nichols, W.C.; Soubrier, F. Genetics and genomics of pulmonary arterial hypertension. Eur. Respir. J. 2019, 53, 1801899.
  13. Ruffenach, G.; O’Connor, E.; Vaillancourt, M.; Hong, J.; Cao, N.; Sarji, S.; Moazeni, S.; Papesh, J.; Grijalva, V.; Cunningham, C.M.; et al. Oral 15-Hydroxyeicosatetraenoic Acid Induces Pulmonary Hypertension in Mice by Triggering T Cell-Dependent Endothelial Cell Apoptosis. Hypertension 2020, 76, 985–996.
  14. Sakao, S.; Tatsumi, K.; Voelkel, N.F. Endothelial cells and pulmonary arterial hypertension: Apoptosis, proliferation, interaction and transdifferentiation. Respir. Res. 2009, 10, 95.
  15. Kim, C.; Seedorf, G.J.; Abman, S.H.; Shepherd, D.P. Heterogeneous response of endothelial cells to insulin-like growth factor 1 treatment is explained by spatially clustered sub-populations. Biol. Open 2019, 8, bio045906.
  16. Sánchez-Duffhues, G.; García de Vinuesa, A.; Ten Dijke, P. Endothelial-to-mesenchymal transition in cardiovascular diseases: Developmental signaling pathways gone awry. Dev. Dyn. Off. Publ. Am. Assoc. Anat. 2018, 247, 492–508.
  17. Mammoto, T.; Muyleart, M.; Konduri, G.G.; Mammoto, A. Twist1 in Hypoxia-induced Pulmonary Hypertension through Transforming Growth Factor-β-Smad Signaling. Am. J. Respir. Cell Mol. Biol. 2018, 58, 194–207.
  18. Ursoli Ferreira, F.; Eduardo Botelho Souza, L.; Hassibe Thomé, C.; Tomazini Pinto, M.; Origassa, C.; Salustiano, S.; Marcel Faça, V.; Olsen Câmara, N.; Kashima, S.; Tadeu Covas, D. Endothelial Cells Tissue-Specific Origins Affects Their Responsiveness to TGF-β2 during Endothelial-to-Mesenchymal Transition. Int. J. Mol. Sci. 2019, 20, 458.
  19. Zhang, H.; Liu, Y.; Yan, L.; Du, W.; Zhang, X.; Zhang, M.; Chen, H.; Zhang, Y.; Zhou, J.; Sun, H.; et al. Bone morphogenetic protein-7 inhibits endothelial-mesenchymal transition in pulmonary artery endothelial cell under hypoxia. J. Cell. Physiol. 2018, 233, 4077–4090.
  20. Hiepen, C.; Jatzlau, J.; Hildebrandt, S.; Kampfrath, B.; Goktas, M. BMPR2 acts as a gatekeeper to protect endothelial cells from increased TGFβ responses and altered cell mechanics. PLoS Biol. 2019, 17, e3000557.
  21. Rol, N.; Kurakula, K.B.; Happé, C.; Bogaard, H.J.; Goumans, M.J. TGF-β and BMPR2 Signaling in PAH: Two Black Sheep in One Family. Int. J. Mol. Sci. 2018, 19, 2585.
  22. Dai, Z.; Zhu, M.M.; Peng, Y.; Machireddy, N.; Evans, C.E.; Machado, R.; Zhang, X.; Zhao, Y.Y. Therapeutic Targeting of Vascular Remodeling and Right Heart Failure in Pulmonary Arterial Hypertension with a HIF-2α Inhibitor. Am. J. Respir. Crit. Care Med. 2018, 198, 1423–1434.
  23. Liu, T.; Zou, X.Z.; Huang, N.; Ge, X.Y.; Yao, M.Z.; Liu, H.; Zhang, Z.; Hu, C.P. miR-27a promotes endothelial-mesenchymal transition in hypoxia-induced pulmonary arterial hypertension by suppressing BMP signaling. Life Sci. 2019, 227, 64–73.
  24. Zhang, H.; Wang, D.; Li, M.; Plecitá-Hlavatá, L.; D’Alessandro, A.; Tauber, J.; Riddle, S.; Kumar, S.; Flockton, A.; McKeon, B.A.; et al. Metabolic and Proliferative State of Vascular Adventitial Fibroblasts in Pulmonary Hypertension Is Regulated Through a MicroRNA-124/PTBP1 (Polypyrimidine Tract Binding Protein 1)/Pyruvate Kinase Muscle Axis. Circulation 2017, 136, 2468–2485.
  25. Zhao, H.; Wang, Y.; Zhang, X.; Guo, Y.; Wang, X. miR-181b-5p inhibits endothelial-mesenchymal transition in monocrotaline-induced pulmonary arterial hypertension by targeting endocan and TGFBR1. Toxicol. Appl. Pharmacol. 2020, 386, 114827.
  26. Happé, C.; Kurakula, K.; Sun, X.Q.; da Silva Goncalves Bos, D. The BMP Receptor 2 in Pulmonary Arterial Hypertension: When and Where the Animal Model Matches the Patient. Cells 2020, 9, 1422.
  27. Bisserier, M.; Mathiyalagan, P.; Zhang, S.; Elmastour, F.; Dorfmüller, P.; Humbert, M.; David, G.; Tarzami, S.; Weber, T.; Perros, F.; et al. Regulation of the Methylation and Expression Levels of the BMPR2 Gene by SIN3a as a Novel Therapeutic Mechanism in Pulmonary Arterial Hypertension. Circulation 2021, 144, 52–73.
  28. Hodgson, J.; Swietlik, E.M.; Salmon, R.M.; Hadinnapola, C.; Nikolic, I.; Wharton, J.; Guo, J.; Liley, J.; Haimel, M.; Bleda, M.; et al. Characterization of GDF2 Mutations and Levels of BMP9 and BMP10 in Pulmonary Arterial Hypertension. Am. J. Respir. Crit. Care Med. 2020, 201, 575–585.
  29. Rol, N.; de Raaf, M.A.; Sun, X.Q.; Kuiper, V.P.; da Silva Gonçalves Bos, D.; Happé, C.; Kurakula, K.; Dickhoff, C.; Thuillet, R.; Tu, L.; et al. Nintedanib improves cardiac fibrosis but leaves pulmonary vascular remodelling unaltered in experimental pulmonary hypertension. Cardiovasc. Res. 2019, 115, 432–439.
  30. Li, C.G.; Mahon, C.; Sweeney, N.M.; Verschueren, E.; Kantamani, V.; Li, D.; Hennigs, J.K.; Marciano, D.P.; Diebold, I.; Abu-Halawa, O.; et al. PPARγ Interaction with UBR5/ATMIN Promotes DNA Repair to Maintain Endothelial Homeostasis. Cell Rep. 2019, 26, 1333–1343.e1337.
  31. Tang, H.; Babicheva, A.; McDermott, K.M.; Gu, Y.; Ayon, R.J.; Song, S.; Wang, Z.; Gupta, A.; Zhou, T.; Sun, X.; et al. Endothelial HIF-2α contributes to severe pulmonary hypertension due to endothelial-to-mesenchymal transition. American journal of physiology. Lung Cell. Mol. Physiol. 2018, 314, L256–L275.
  32. Oliveira, S.D.S.; Chen, J.; Castellon, M.; Mao, M.; Raj, J.U.; Comhair, S.; Erzurum, S.; Silva, C.L.M.; Machado, R.F.; Bonini, M.G.; et al. Injury-Induced Shedding of Extracellular Vesicles Depletes Endothelial Cells of Cav-1 (Caveolin-1) and Enables TGF-β (Transforming Growth Factor-β)-Dependent Pulmonary Arterial Hypertension. Arterioscler. Thromb. Vasc. Biol. 2019, 39, 1191–1202.
  33. Yu, X.; Chen, X.; Zheng, X.D.; Zhang, J.; Zhao, X.; Liu, Y.; Zhang, H.; Zhang, L.; Yu, H.; Zhang, M.; et al. Growth Differentiation Factor 11 Promotes Abnormal Proliferation and Angiogenesis of Pulmonary Artery Endothelial Cells. Hypertension 2018, 71, 729–741.
  34. Kurakula, K.; Sun, X.Q.; Happé, C.; da Silva Goncalves Bos, D.; Szulcek, R.; Schalij, I.; Wiesmeijer, K.C.; Lodder, K.; Tu, L.; Guignabert, C. Prevention of progression of pulmonary hypertension by the Nur77 agonist 6-mercaptopurine: Role of BMP signalling. Eur. Respir. J. 2019, 54, 1802400.
  35. Wang, E.L.; Jia, M.M.; Luo, F.M.; Li, T.; Peng, J.J.; Luo, X.J.; Song, F.L.; Yang, J.F.; Peng, J.; Liu, B. Coordination between NADPH oxidase and vascular peroxidase 1 promotes dysfunctions of endothelial progenitor cells in hypoxia-induced pulmonary hypertensive rats. Eur. J. Pharmacol. 2019, 857, 172459.
  36. Goyanes, A.M.; Moldobaeva, A.; Marimoutou, M.; Varela, L.C.; Wang, L.; Johnston, L.F.; Aladdin, M.M.; Peloquin, G.L.; Kim, B.S.; Damarla, M.; et al. Functional Impact of Human Genetic Variants of COL18A1/Endostatin on Pulmonary Endothelium. Am. J. Respir. Cell Mol. Biol. 2020, 62, 524–534.
  37. Park, C.S.; Kim, S.H.; Yang, H.Y.; Kim, J.H.; Schermuly, R.T.; Cho, Y.S.; Kang, H.; Park, J.H.; Lee, E. Sox17 Deficiency Promotes Pulmonary Arterial Hypertension via HGF/c-Met Signaling. Circ. Res. 2022, 131, 792–806.
  38. Kondababu, K.; Smolders, V.F.E.D.; Olga, T.; Wouter, J.J.; Quax, P.H.A.; MarieJosé, G. Endothelial Dysfunction in Pulmonary Hypertension: Cause or Consequence? Biomedicines 2021, 9, 57.
  39. Sakamaki, F.; Kyotani, S.; Nagaya, N.; Sato, N.; Oya, H.; Satoh, T.; Nakanishi, N. Increased plasma P-selectin and decreased thrombomodulin in pulmonary arterial hypertension were improved by continuous prostacyclin therapy. Circulation 2000, 102, 2720–2725.
  40. Maeda, N.Y.; Clavé, M.M.; Bydlowski, S.P.; Lopes, A.A. Decreased circulating thrombomodulin is improved by tadalafil therapy in hypoxemic patients with advanced pulmonary arterial hypertension. Thromb. Res. 2016, 146, 15–19.
  41. Pan, Y.Y.; Yang, J.X.; Mao, W.; Wang, X.X. RNA-binding protein SFPQ cooperates with HDAC1 to suppress CD40 transcription in pulmonary adventitial fibroblasts. Cell Biol. Int. 2019, 44, 166–176.
  42. Kovacs, L.; Cao, Y.; Han, W.; Meadows, L.; Kovacs-Kasa, A.; Kondrikov, D.; Verin, A.D.; Barman, S.A.; Dong, Z.; Huo, Y.; et al. PFKFB3 in Smooth Muscle Promotes Vascular Remodeling in Pulmonary Arterial Hypertension. Am. J. Respir. Crit. Care Med. 2019, 200, 617–627.
  43. Sun, X.; Kumar, S.; Sharma, S.; Aggarwal, S.; Lu, Q.; Gross, C.; Rafikova, O.; Lee, S.G.; Dasarathy, S.; Hou, Y.; et al. Endothelin-1 induces a glycolytic switch in pulmonary arterial endothelial cells via the mitochondrial translocation of endothelial nitric oxide synthase. Am. J. Respir. Cell Mol. Biol. 2014, 50, 1084–1095.
  44. Yu, Q.; Tai, Y.Y.; Tang, Y.; Zhao, J.; Negi, V.; Culley, M.K.; Pilli, J.; Sun, W.; Brugger, K.; Mayr, J.; et al. BOLA (BolA Family Member 3) Deficiency Controls Endothelial Metabolism and Glycine Homeostasis in Pulmonary Hypertension. Circulation 2019, 139, 2238–2255.
  45. Bertero, T.; Oldham, W.M.; Cottrill, K.A.; Pisano, S.; Vanderpool, R.R.; Yu, Q.; Zhao, J.; Tai, Y.; Tang, Y.; Zhang, Y.Y.; et al. Vascular stiffness mechanoactivates YAP/TAZ-dependent glutaminolysis to drive pulmonary hypertension. J. Clin. Investig. 2016, 126, 3313–3335.
  46. Thoré, P.; Girerd, B.; Jaïs, X.; Savale, L.; Ghigna, M.R.; Eyries, M.; Levy, M.; Ovaert, C.; Servettaz, A. Phenotype and outcome of pulmonary arterial hypertension patients carrying a TBX4 mutation. Eur. Respir. J. 2020, 55, 1902340.
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to : , , , , , , , , ,
View Times: 494
Revisions: 3 times (View History)
Update Date: 24 Apr 2023
Video Production Service