Abid S, Marcos E, Parpaleix A, Amsellem V, Breau M, Houssaini A, Vienney N, Lefevre M, Derumeaux G, Evans S, Hubeau C, Delcroix M, Quarck R, Adnot S, Lipskaia L (2019) CCR2/CCR5-mediated macrophage-smooth muscle cell crosstalk in pulmonary hypertension. Eur Respir J 54(4):1802308

Google Scholar 

Awad KS, Elinoff JM, Wang S, Gairhe S, Ferreyra GA, Cai R, Sun J, Solomon MA, Danner RL (2016) Raf/ERK drives the proliferative and invasive phenotype of BMPR2-silenced pulmonary artery endothelial cells. Am J Physiol Lung Cell Mol Physiol 310(2):L187–L201

Google Scholar 

Bai P, Lyu L, Yu T, Zuo C, Fu J, He Y, Wan Q, Wan N, Jia D, Lyu A (2019) Macrophage-derived legumain promotes pulmonary hypertension by activating the MMP (matrix metalloproteinase)-2/TGF (transforming growth factor)-β1 signaling. Arterioscler Thromb Vasc Biol 39(4):e130–e145

Google Scholar 

Batool M, Berghausen EM, Zierden M, Vantler M, Schermuly RT, Baldus S, Rosenkranz S, Ten Freyhaus H (2020) The six-transmembrane protein Stamp2 ameliorates pulmonary vascular remodeling and pulmonary hypertension in mice. Basic Res Cardiol 115(6):68

Google Scholar 

Böger R, Hannemann J (2020) Dual role of the L-arginine-ADMA-NO pathway in systemic hypoxic vasodilation and pulmonary hypoxic vasoconstriction. Pulm Circ 10(2):2045894020918850

Google Scholar 

Bordenave J, Thuillet R, Tu L, Phan C, Cumont A, Marsol C, Huertas A, Savale L, Hibert M, Galzi J-L, Bonnet D, Humbert M, Frossard N, Guignabert C (2020) Neutralization of CXCL12 attenuates established pulmonary hypertension in rats. Cardiovasc Res 116(3):686–697

Google Scholar 

Byrne AJ, Maher TM, Lloyd CM (2016) Pulmonary macrophages: a new therapeutic pathway in fibrosing lung disease? Trends Mol Med 22(4):303–316

Google Scholar 

Chan SY, Loscalzo J (2008) Pathogenic mechanisms of pulmonary arterial hypertension. J Mol Cell Cardiol 44(1):14–30

Google Scholar 

Chen Q, Liu Y (2020) Heterogeneous groups of alveolar type II cells in lung homeostasis and repair. Am J Physiol Cell Physiol 319(6):C991–C996

Google Scholar 

Chen S, Rong M, Platteau A, Hehre D, Smith H, Ruiz P, Whitsett J, Bancalari E, Wu S (2011) CTGF disrupts alveolarization and induces pulmonary hypertension in neonatal mice: implication in the pathogenesis of severe bronchopulmonary dysplasia. Am J Physiol Lung Cell Mol Physiol 300(3):L330–L340

Google Scholar 

Dai Z, Li M, Wharton J, Zhu MM, Zhao Y-Y (2016) Prolyl-4 hydroxylase 2 (PHD2) deficiency in endothelial cells and hematopoietic cells induces obliterative vascular remodeling and severe pulmonary arterial hypertension in mice and humans through hypoxia-inducible factor-2α. Circulation 133(24):2447–2458

Google Scholar 

Dai Z, Zhu MM, Peng Y, Jin H, Machireddy N, Qian Z, Zhang X, Zhao Y-Y (2018) Endothelial and smooth muscle cell interaction via FoxM1 signaling mediates vascular remodeling and pulmonary hypertension. Am J Respir Crit Care Med 198(6):788–802

Google Scholar 

Deng L, Blanco FJ, Stevens H, Lu R, Caudrillier A, McBride M, McClure JD, Grant J, Thomas M, Frid M, Stenmark K, White K, Seto AG, Morrell NW, Bradshaw AC, MacLean MR, Baker AH (2015) MicroRNA-143 activation regulates smooth muscle and endothelial cell crosstalk in pulmonary arterial hypertension. Circ Res 117(10):870–883

Google Scholar 

Dickinson MG, Bartelds B, Molema G, Borgdorff MA, Boersma B, Takens J, Weij M, Wichers P, Sietsma H, Berger RMF (2011) Egr-1 expression during neointimal development in flow-associated pulmonary hypertension. Am J Pathol 179(5):2199–2209

Google Scholar 

Dreymueller D, Martin C, Schumacher J, Groth E, Boehm JK, Reiss LK, Uhlig S, Ludwig A (2014) Smooth muscle cells relay acute pulmonary inflammation via distinct ADAM17/ErbB axes. J Immunol 192(2):722–731

Google Scholar 

El Kasmi KC, Pugliese SC, Riddle SR, Poth JM, Anderson AL, Frid MG, Li M, Pullamsetti SS, Savai R, Nagel MA, Fini MA, Graham BB, Tuder RM, Friedman JE, Eltzschig HK, Sokol RJ, Stenmark KR (2014) Adventitial fibroblasts induce a distinct proinflammatory/profibrotic macrophage phenotype in pulmonary hypertension. J Immunol 193(2):597–609

Google Scholar 

Evans CE, Cober ND, Dai Z, Stewart DJ, Zhao Y-Y (2021) Endothelial cells in the pathogenesis of pulmonary arterial hypertension. Eur Respir J 58(3):2003957

Google Scholar 

Fiscon G, Conte F, Farina L, Paci P (2018) Network-based approaches to explore complex biological systems towards network medicine. Genes 9(9):437

Google Scholar 

Gao Y, Chen T, Raj JU (2016) Endothelial and smooth muscle cell interactions in the pathobiology of pulmonary hypertension. Am J Respir Cell Mol Biol 54(4):451–460

Google Scholar 

Grimmer B, Kuebler WM (2017) The endothelium in hypoxic pulmonary vasoconstriction. J Appl Physiol (1985) 123(6):1635–1646

Google Scholar 

Gu J, Zhang H, Ji B, Jiang H, Zhao T, Jiang R, Zhang Z, Tan S, Ahmed A, Gu Y (2017) Vesicle miR-195 derived from endothelial cells inhibits expression of serotonin transporter in vessel smooth muscle cells. Sci Rep 7:43546

Google Scholar 

Guignabert C, Tu L, Girerd B, Ricard N, Huertas A, Montani D, Humbert M (2015) New molecular targets of pulmonary vascular remodeling in pulmonary arterial hypertension: importance of endothelial communication. Chest 147(2):529–537

Google Scholar 

Hansmann G (2017) Pulmonary hypertension in infants, children, and young adults. J Am Coll Cardiol 69(20):2551–2569

Google Scholar 

Hoeper MM, Ghofrani H-A, Grünig E, Klose H, Olschewski H, Rosenkranz S (2017) Pulmonary hypertension. Dtsch Arzteblatt Int 114(5):73–84

Google Scholar 

Hou J, Ji J, Chen X, Cao H, Tan Y, Cui Y, Xiang Z, Han X (2021) Alveolar epithelial cell-derived sonic hedgehog promotes pulmonary fibrosis through OPN-dependent alternative macrophage activation. FEBS J 288(11):3530–3546

Google Scholar 

Hough RF, Bhattacharya S, Bhattacharya J (2018) Crosstalk signaling between alveoli and capillaries. Pulm Circ 8(3):2045894018783735

Google Scholar 

Hsu JY, Major JL, Riching AS, Sen R, Pires da Silva J, Bagchi RA (2020) Beyond the genome: challenges and potential for epigenetics-driven therapeutic approaches in pulmonary arterial hypertension. Biochem Cell Biol = Biochim Biol Cell 98(6):631–646

Google Scholar 

Huang S, Yue Y, Feng K, Huang X, Li H, Hou J, Yang S, Huang S, Liang M, Chen G, Wu Z (2020) Conditioned medium from M2b macrophages modulates the proliferation, migration, and apoptosis of pulmonary artery smooth muscle cells by deregulating the PI3K/Akt/FoxO3a pathway. PeerJ 8:e9110

Google Scholar 

Huertas A, Perros F, Tu L, Cohen-Kaminsky S, Montani D, Dorfmüller P, Guignabert C, Humbert M (2014) Immune dysregulation and endothelial dysfunction in pulmonary arterial hypertension: a complex interplay. Circulation 129(12):1332–1340

Google Scholar 

Hwang I (2013) Cell-cell communication via extracellular membrane vesicles and its role in the immune response. Mol Cells 36(2):105–111

Google Scholar 

Jiao Y, Li Z, Loughran PA, Fan EK, Scott MJ, Li Y, Billiar TR, Wilson MA, Shi X, Fan J (2018) Frontline science: macrophage-derived exosomes promote neutrophil necroptosis following hemorrhagic shock. J Leukoc Biol 103(2):175–183

Google Scholar 

Jimenez SA, Piera-Velazquez S (2016) Endothelial to mesenchymal transition (EndoMT) in the pathogenesis of systemic sclerosis-associated pulmonary fibrosis and pulmonary arterial hypertension. Myth or reality? Matrix Biol 51:26–36

Google Scholar 

Kato A, Okura T, Hamada C, Miyoshi S, Katayama H, Higaki J, Ito R (2014) Cell stress induces upregulation of osteopontin via the ERK pathway in type II alveolar epithelial cells. PLoS One 9(6):e100106

Google Scholar 

Kim D, George MP (2019) Pulmonary hypertension. Med Clin North Am 103(3):413–423

Google Scholar 

Kuebler WM, Bonnet S, Tabuchi A (2018) Inflammation and autoimmunity in pulmonary hypertension: is there a role for endothelial adhesion molecules? (2017 Grover conference series). Pulm Circ 8(2):2045893218757596

Google Scholar 

Labrousse-Arias D, Castillo-González R, Rogers NM, Torres-Capelli M, Barreira B, Aragonés J, Cogolludo Á, Isenberg JS, Calzada MJ (2016) HIF-2α-mediated induction of pulmonary thrombospondin-1 contributes to hypoxia-driven vascular remodelling and vasoconstriction. Cardiovasc Res 109(1):115–130

Google Scholar 

Larson-Casey JL, He C, Carter AB (2020) Mitochondrial quality control in pulmonary fibrosis. Redox Biol 33:101426

Google Scholar 

Le Hiress M, Tu L, Ricard N, Phan C, Thuillet R, Fadel E, Dorfmüller P, Montani D, de Man F, Humbert M, Huertas A, Guignabert C (2015) Proinflammatory signature of the dysfunctional endothelium in pulmonary hypertension. Role of the macrophage migration inhibitory factor/CD74 complex. Am J Respir Crit Care Med 192(8):983–997

Google Scholar 

Lee J, Arisi I, Puxeddu E, Mramba LK, Amicosante M, Swaisgood CM, Pallante M, Brantly ML, Sköld CM, Saltini C (2018) Bronchoalveolar lavage (BAL) cells in idiopathic pulmonary fibrosis express a complex pro-inflammatory, pro-repair, angiogenic activation pattern, likely associated with macrophage iron accumulation. PLoS One 13(4):e0194803

Google Scholar 

Li S, Zhai C, Shi W, Feng W, Xie X, Pan Y, Wang J, Yan X, Chai L, Wang Q, Zhang Q, Liu P, Li M (2020) Leukotriene B induces proliferation of rat pulmonary arterial smooth muscle cells via modulating GSK-3β/β-catenin pathway. Eur J Pharmacol 867:172823

Google Scholar 

Li M, Riddle S, Kumar S, Poczobutt J, McKeon BA, Frid MG, Ostaff M, Reisz JA, Nemkov T, Fini MA, Laux A, Hu C-J, El Kasmi KC, D'Alessandro A, Brown RD, Zhang H, Stenmark KR (2021) Microenvironmental regulation of macrophage transcriptomic and metabolomic profiles in pulmonary hypertension. Front Immunol 12:640718

Google Scholar 

Liang L-Y, Wang M-M, Liu M, Zhao W, Wang X, Shi L, Zhu M-J, Zhao Y-L, Liu L, Maurya P, Wang Y (2020) Chronic toxicity of methamphetamine: oxidative remodeling of pulmonary arteries. Toxicol In Vitro 62:104668

Google Scholar 

Lin Q, Fan C, Gomez-Arroyo J, Van Raemdonck K, Meuchel LW, Skinner JT, Everett AD, Fang X, Macdonald AA, Yamaji-Kegan K, Johns RA (2019) HIMF (hypoxia-induced mitogenic factor) signaling mediates the HMGB1 (high mobility group box 1)-dependent endothelial and smooth muscle cell crosstalk in pulmonary hypertension. Arterioscler Thromb Vasc Biol 39(12):2505–2519

Google Scholar 

Liu Y, Zhang H, Yan L, Du W, Zhang M, Chen H, Zhang L, Li G, Li J, Dong Y, Zhu D (2018) MMP-2 and MMP-9 contribute to the angiogenic effect produced by hypoxia/15-HETE in pulmonary endothelial cells. J Mol Cell Cardiol 121:36–50

Google Scholar 

Liu F, Peng W, Chen J, Xu Z, Jiang R, Shao Q, Zhao N, Qian K (2021) Exosomes derived from alveolar epithelial cells promote alveolar macrophage activation mediated by miR-92a-3p in sepsis-induced acute lung injury. Front Cell Infect Microbiol 11:646546

Google Scholar 

Makino A, Firth AL, Yuan JXJ (2011) Endothelial and smooth muscle cell ion channels in pulmonary vasoconstriction and vascular remodeling. Compr Physiol 1(3):1555–1602

Google Scholar 

Miyagawa K, Shi M, Chen P-I, Hennigs JK, Zhao Z, Wang M, Li CG, Saito T, Taylor S, Sa S, Cao A, Wang L, Snyder MP, Rabinovitch M (2019) Smooth muscle contact drives endothelial regeneration by BMPR2-Notch1-mediated metabolic and epigenetic changes. Circ Res 124(2):211–224

Google Scholar 

Montani D, Lau EM, Dorfmüller P, Girerd B, Jaïs X, Savale L, Perros F, Nossent E, Garcia G, Parent F, Fadel E, Soubrier F, Sitbon O, Simonneau G, Humbert M (2016) Pulmonary veno-occlusive disease. Eur Respir J 47(5):1518–1534

Google Scholar 

Mumby S, Gambaryan N, Meng C, Perros F, Humbert M, Wort SJ, Adcock IM (2017) Bromodomain and extra-terminal protein mimic JQ1 decreases inflammation in human vascular endothelial cells: implications for pulmonary arterial hypertension. Respirology 22(1):157–164

Google Scholar 

Napoli C, Benincasa G, Loscalzo J (2019) Epigenetic inheritance underlying pulmonary arterial hypertension. Arterioscler Thromb Vasc Biol 39(4):653–664

Google Scholar 

Oliveira SDS, Castellon M, Chen J, Bonini MG, Gu X, Elliott MH, Machado RF, Minshall RD (2017) Inflammation-induced caveolin-1 and BMPRII depletion promotes endothelial dysfunction and TGF-β-driven pulmonary vascular remodeling. Am J Physiol Lung Cell Mol Physiol 312(5):L760–L771

Google Scholar 

Pasha Q (2014) Saudi guidelines on the diagnosis and treatment of pulmonary hypertension: genetics of pulmonary hypertension. Ann Thorac Med 9(Suppl 1):S16–S20

Google Scholar 

Perros F, Ranchoux B, Izikki M, Bentebbal S, Happé C, Antigny F, Jourdon P, Dorfmüller P, Lecerf F, Fadel E, Simonneau G, Humbert M, Bogaard HJ, Eddahibi S (2015) Nebivolol for improving endothelial dysfunction, pulmonary vascular remodeling, and right heart function in pulmonary hypertension. J Am Coll Cardiol 65(7):668–680

Google Scholar 

Peters-Golden M, Henderson WR (2007) Leukotrienes. N Engl J Med 357(18):1841–1854

Google Scholar 

Petrusca DN, Van Demark M, Gu Y, Justice MJ, Rogozea A, Hubbard WC, Petrache I (2014) Smoking exposure induces human lung endothelial cell adaptation to apoptotic stress. Am J Respir Cell Mol Biol 50(3):513–525

Google Scholar 

Pi L, Fu C, Lu Y, Zhou J, Jorgensen M, Shenoy V, Lipson KE, Scott EW, Bryant AJ (2018) Vascular endothelial cell-specific connective tissue growth factor (CTGF) is necessary for development of chronic hypoxia-induced pulmonary hypertension. Front Physiol 9:138

Google Scholar 

Pu X, Lin X, Duan X, Wang J, Shang J, Yun H, Chen Z (2020) Oxidative and endoplasmic reticulum stress responses to chronic high-altitude exposure during the development of high-altitude pulmonary hypertension. High Alt Med Biol 21(4):378–387

Google Scholar 

Pulido T, Zayas N, de Mendieta MA, Plascencia K, Escobar J (2016) Medical therapies for pulmonary arterial hypertension. Heart Fail Rev 21(3):273–283

Google Scholar 

Qian J, Tian W, Jiang X, Tamosiuniene R, Sung YK, Shuffle EM, Tu AB, Valenzuela A, Jiang S, Zamanian RT, Fiorentino DF, Voelkel NF, Peters-Golden M, Stenmark KR, Chung L, Rabinovitch M, Nicolls MR (2015) Leukotriene B4 activates pulmonary artery adventitial fibroblasts in pulmonary hypertension. Hypertension 66(6):1227–1239