The fate and role of the pericytes in myocardial diseases.
angiogenesis
fibrosis
heart failure
inflammation
pericyte
Journal
European journal of clinical investigation
ISSN: 1365-2362
Titre abrégé: Eur J Clin Invest
Pays: England
ID NLM: 0245331
Informations de publication
Date de publication:
08 Apr 2024
08 Apr 2024
Historique:
revised:
24
03
2024
received:
20
02
2024
accepted:
25
03
2024
medline:
8
4
2024
pubmed:
8
4
2024
entrez:
8
4
2024
Statut:
aheadofprint
Résumé
The adult mammalian heart contains a large population of pericytes that play important roles in homeostasis and disease. In the normal heart, pericytes regulate microvascular permeability and flow. Myocardial diseases are associated with marked alterations in pericyte phenotype and function. This review manuscript discusses the role of pericytes in cardiac homeostasis and disease. Following myocardial infarction (MI), cardiac pericytes participate in all phases of cardiac repair. During the inflammatory phase, pericytes may secrete cytokines and chemokines and may regulate leukocyte trafficking, through formation of intercellular gaps that serve as exit points for inflammatory cells. Moreover, pericyte contraction induces microvascular constriction, contributing to the pathogenesis of 'no-reflow' in ischemia and reperfusion. During the proliferative phase, pericytes are activated by growth factors, such as transforming growth factor (TGF)-β and contribute to fibrosis, predominantly through secretion of fibrogenic mediators. A fraction of pericytes acquires fibroblast identity but contributes only to a small percentage of infarct fibroblasts and myofibroblasts. As the scar matures, pericytes form a coat around infarct neovessels, promoting stabilization of the vasculature. Pericytes may also be involved in the pathogenesis of chronic heart failure, by regulating inflammation, fibrosis, angiogenesis and myocardial perfusion. Pericytes are also important targets of viral infections (such as SARS-CoV2) and may be implicated in the pathogenesis of cardiac complications of COVID19. Considering their role in myocardial inflammation, fibrosis and angiogenesis, pericytes may be promising therapeutic targets in myocardial disease.
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
e14204Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL76246
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL149407
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL85440
Pays : United States
Informations de copyright
© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.
Références
Rouget C. Mémoire sur le développement, la structure et les propriétés physiologique des cappilaires sanguins et lymphatiques. Arch Physiol Norm Path. 1873;5:603‐663.
Zimmermann KW. Der feinere Bau der Blutkapillaren. Z Anat Entwicklungsgesch. 1923;68:29‐109.
Armulik A, Genove G, Betsholtz C. Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev Cell. 2011;21:193‐215.
Dessalles CA, Babataheri A, Barakat AI. Pericyte mechanics and mechanobiology. J Cell Sci. 2021;134(6):jcs240226. doi:10.1242/jcs.240226
Attwell D, Mishra A, Hall CN, O'Farrell FM, Dalkara T. What is a pericyte? J Cereb Blood Flow Metab. 2016;36:451‐455.
Dulmovits BM, Herman IM. Microvascular remodeling and wound healing: a role for pericytes. Int J Biochem Cell Biol. 2012;44:1800‐1812.
Yamazaki T, Mukouyama YS. Tissue specific origin, development, and pathological perspectives of pericytes. Front Cardiovasc Med. 2018;5:78.
Sims DE. The pericyte – a review. Tissue Cell. 1986;18:153‐174.
Hartmann DA, Underly RG, Grant RI, Watson AN, Lindner V, Shih AY. Pericyte structure and distribution in the cerebral cortex revealed by high‐resolution imaging of transgenic mice. Neurophotonics. 2015;2:041402.
Nehme A, Edelman J. Dexamethasone inhibits high glucose‐, TNF‐alpha‐, and IL‐1beta‐induced secretion of inflammatory and angiogenic mediators from retinal microvascular pericytes. Invest Ophthalmol Vis Sci. 2008;49:2030‐2038.
Wang S, Cao C, Chen Z, et al. Pericytes regulate vascular basement membrane remodeling and govern neutrophil extravasation during inflammation. PLoS One. 2012;7:e45499.
Ren S, Johnson BG, Kida Y, et al. LRP‐6 is a coreceptor for multiple fibrogenic signaling pathways in pericytes and myofibroblasts that are inhibited by DKK‐1. Proc Natl Acad Sci USA. 2013;110:1440‐1445.
Kramann R, Schneider RK, DiRocco DP, et al. Perivascular Gli1+ progenitors are key contributors to injury‐induced organ fibrosis. Cell Stem Cell. 2015;16:51‐66.
Campagnolo P, Katare R, Madeddu P. Realities and misconceptions on the pericytes role in tissue repair. Regen Med. 2018;13:119‐122.
Paquet‐Fifield S, Schluter H, Li A, et al. A role for pericytes as microenvironmental regulators of human skin tissue regeneration. J Clin Invest. 2009;119:2795‐2806.
Sun R, Kong X, Qiu X, Huang C, Wong PP. The emerging roles of pericytes in modulating tumor microenvironment. Front Cell Dev Biol. 2021;9:676342.
Rayner SG, Hung CF, Liles WC, Altemeier WA. Lung pericytes as mediators of inflammation. Am J Physiol Lung Cell Mol Physiol. 2023;325:L1‐L8.
Nees S, Weiss DR, Senftl A, et al. Isolation, bulk cultivation, and characterization of coronary microvascular pericytes: the second most frequent myocardial cell type in vitro. Am J Physiol Heart Circ Physiol. 2012;302:H69‐H84.
Pinto AR, Ilinykh A, Ivey MJ, et al. Revisiting cardiac cellular composition. Circ Res. 2016;118:400‐409.
Popescu LM, Curici A, Wang E, Zhang H, Hu S, Gherghiceanu M. Telocytes and putative stem cells in ageing human heart. J Cell Mol Med. 2015;19:31‐45.
Forbes MS, Rennels ML, Nelson E. Ultrastructure of pericytes in mouse heart. Am J Anat. 1977;149:47‐70.
Higuchi K, Hashizume H, Aizawa Y, Ushiki T. Scanning electron microscopic studies of the vascular smooth muscle cells and pericytes in the rat heart. Arch Histol Cytol. 2000;63:115‐126.
Litvinukova M, Talavera‐Lopez C, Maatz H, et al. Cells of the adult human heart. Nature. 2020;588:466‐472.
Grant RI, Hartmann DA, Underly RG, Berthiaume AA, Bhat NR, Shih AY. Organizational hierarchy and structural diversity of microvascular pericytes in adult mouse cortex. J Cereb Blood Flow Metab. 2019;39:411‐425.
Krueger M, Bechmann I. CNS pericytes: concepts, misconceptions, and a way out. Glia. 2010;58:1‐10.
O'Farrell FM, Mastitskaya S, Hammond‐Haley M, Freitas F, Wah WR, Attwell D. Capillary pericytes mediate coronary no‐reflow after myocardial ischaemia. eLife. 2017;6:e29280.
Ozerdem U, Grako KA, Dahlin‐Huppe K, Monosov E, Stallcup WB. NG2 proteoglycan is expressed exclusively by mural cells during vascular morphogenesis. Dev Dyn. 2001;222:218‐227.
Zhao G, Joca HC, Lederer WJ. Dynamic measurement and imaging of capillaries, arterioles, and pericytes in mouse heart. J Vis Exp. 2020;(161). doi:10.3791/61566
Birbrair A, Zhang T, Wang ZM, et al. Skeletal muscle pericyte subtypes differ in their differentiation potential. Stem Cell Res. 2013;10:67‐84.
Birbrair A, Zhang T, Files DC, et al. Type‐1 pericytes accumulate after tissue injury and produce collagen in an organ‐dependent manner. Stem Cell Res Ther. 2014;5:122.
Horiuchi K, Kano K, Minoshima A, et al. Pericyte‐specific deletion of ninjurin‐1 induces fragile vasa vasorum formation and enhances intimal hyperplasia of injured vasculature. Am J Physiol Heart Circ Physiol. 2021;320:H2438‐H2447.
Alex L, Tuleta I, Harikrishnan V, Frangogiannis NG. Validation of specific and reliable genetic tools to identify, label, and target cardiac pericytes in mice. J Am Heart Assoc. 2022;11:e023171.
Chen Q, Zhang H, Liu Y, et al. Endothelial cells are progenitors of cardiac pericytes and vascular smooth muscle cells. Nat Commun. 2016;7:12422.
Cuervo H, Pereira B, Nadeem T, et al. PDGFRbeta‐P2A‐CreER(T2) mice: a genetic tool to target pericytes in angiogenesis. Angiogenesis. 2017;20:655‐662.
Spiranec K, Chen W, Werner F, et al. Endothelial C‐type natriuretic peptide acts on pericytes to regulate microcirculatory flow and blood pressure. Circulation. 2018;138:494‐508.
Henderson NC, Arnold TD, Katamura Y, et al. Targeting of alphav integrin identifies a core molecular pathway that regulates fibrosis in several organs. Nat Med. 2013;19:1617‐1624.
Sciurba JC, Gieseck RL, Jiwrajka N, et al. Fibroblast‐specific integrin‐alpha V differentially regulates type 17 and type 2 driven inflammation and fibrosis. J Pathol. 2019;248:16‐29.
Guimaraes‐Camboa N, Cattaneo P, Sun Y, et al. Pericytes of multiple organs do not behave as mesenchymal stem cells in vivo. Cell Stem Cell. 2017;20:345‐359.e5.
Kapoor N, Liang W, Marban E, Cho HC. Direct conversion of quiescent cardiomyocytes to pacemaker cells by expression of Tbx18. Nat Biotechnol. 2013;31:54‐62.
Cai CL, Martin JC, Sun Y, et al. A myocardial lineage derives from Tbx18 epicardial cells. Nature. 2008;454:104‐108.
Hartmann DA, Underly RG, Watson AN, Shih AY. A murine toolbox for imaging the neurovascular unit. Microcirculation. 2015;22:168‐182.
Chen WC, Baily JE, Corselli M, et al. Human myocardial pericytes: multipotent mesodermal precursors exhibiting cardiac specificity. Stem Cells. 2015;33:557‐573.
Wang Z, Xu Q, Zhang N, Du X, Xu G, Yan X. CD146, from a melanoma cell adhesion molecule to a signaling receptor. Signal Transduct Target Ther. 2020;5:148.
Ren G, Michael LH, Entman ML, Frangogiannis NG. Morphological characteristics of the microvasculature in healing myocardial infarcts. J Histochem Cytochem. 2002;50:71‐79.
Anfosso F, Bardin N, Frances V, et al. Activation of human endothelial cells via S‐endo‐1 antigen (CD146) stimulates the tyrosine phosphorylation of focal adhesion kinase p125(FAK). J Biol Chem. 1998;273:26852‐26856.
Alarcon‐Martinez L, Yilmaz‐Ozcan S, Yemisci M, et al. Capillary pericytes express alpha‐smooth muscle actin, which requires prevention of filamentous‐actin depolymerization for detection. eLife. 2018;7:e34861.
Verbeek MM, Otte‐Holler I, Wesseling P, Ruiter DJ, de Waal RM. Induction of alpha‐smooth muscle actin expression in cultured human brain pericytes by transforming growth factor‐beta 1. Am J Pathol. 1994;144:372‐382.
Desmouliere A, Geinoz A, Gabbiani F, Gabbiani G. Transforming growth factor‐beta 1 induces alpha‐smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts. J Cell Biol. 1993;122:103‐111.
Hinz B. Myofibroblasts. Exp Eye Res. 2016;142:56‐70.
Willems IE, Havenith MG, De Mey JG, Daemen MJ. The alpha‐smooth muscle actin‐positive cells in healing human myocardial scars. Am J Pathol. 1994;145:868‐875.
Frangogiannis NG, Michael LH, Entman ML. Myofibroblasts in reperfused myocardial infarcts express the embryonic form of smooth muscle myosin heavy chain (SMemb). Cardiovasc Res. 2000;48:89‐100.
Barron L, Gharib SA, Duffield JS. Lung pericytes and resident fibroblasts: busy multitaskers. Am J Pathol. 2016;186:2519‐2531.
Geevarghese A, Herman IM. Pericyte‐endothelial crosstalk: implications and opportunities for advanced cellular therapies. Transl Res. 2014;163:296‐306.
Crisan M, Yap S, Casteilla L, et al. A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell. 2008;3:301‐313.
Muhl L, Genove G, Leptidis S, et al. Single‐cell analysis uncovers fibroblast heterogeneity and criteria for fibroblast and mural cell identification and discrimination. Nat Commun. 2020;11:3953.
Edelman DA, Jiang Y, Tyburski J, Wilson RF, Steffes C. Pericytes and their role in microvasculature homeostasis. J Surg Res. 2006;135:305‐311.
Armulik A, Genove G, Mae M, et al. Pericytes regulate the blood‐brain barrier. Nature. 2010;468:557‐561.
Torok O, Schreiner B, Schaffenrath J, et al. Pericytes regulate vascular immune homeostasis in the CNS. Proc Natl Acad Sci USA. 2021;118:e2016587118.
Joyce NC, Haire MF, Palade GE. Contractile proteins in pericytes. I. Immunoperoxidase localization of tropomyosin. J Cell Biol. 1985;100:1379‐1386.
Spiranec Spes K, Chen W, Krebes L, et al. Heart‐microcirculation connection: effects of ANP (atrial natriuretic peptide) on pericytes participate in the acute and chronic regulation of arterial blood pressure. Hypertension. 2020;76:1637‐1648.
Hellstrom M, Kalen M, Lindahl P, Abramsson A, Betsholtz C. Role of PDGF‐B and PDGFR‐beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. Development. 1999;126:3047‐3055.
Cornuault L, Herion FX, Bourguignon C, et al. Partial mural cell ablation disrupts coronary vasculature integrity and induces systolic dysfunction. J Am Heart Assoc. 2023;12:e029279.
Simmonds SJ, Grootaert MOJ, Cuijpers I, et al. Pericyte loss initiates microvascular dysfunction in the development of diastolic dysfunction. Eur Heart J Open. 2024;4:oead129.
Chintalgattu V, Rees ML, Culver JC, et al. Coronary microvascular pericytes are the cellular target of sunitinib malate‐induced cardiotoxicity. Sci Transl Med. 2013;5:187ra169.
Lee LL, Khakoo AY, Chintalgattu V. Cardiac pericytes function as key vasoactive cells to regulate homeostasis and disease. FEBS Open Bio. 2021;11:207‐225.
Zhao G, Joca HC, Nelson MT, Lederer WJ. ATP‐ and voltage‐dependent electro‐metabolic signaling regulates blood flow in heart. Proc Natl Acad Sci USA. 2020;117:7461‐7470.
DeWood MA, Spores J, Notske R, et al. Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction. N Engl J Med. 1980;303:897‐902.
Frangogiannis NG. Pathophysiology of myocardial infarction. Compr Physiol. 2015;5:1841‐1875.
Bentzon JF, Otsuka F, Virmani R, Falk E. Mechanisms of plaque formation and rupture. Circ Res. 2014;114:1852‐1866.
Arslan F, Smeets MB, O'Neill LA, et al. Myocardial ischemia/reperfusion injury is mediated by leukocytic toll‐like receptor‐2 and reduced by systemic administration of a novel anti‐toll‐like receptor‐2 antibody. Circulation. 2010;121:80‐90.
Frangogiannis NG, Mendoza LH, Lindsey ML, et al. IL‐10 is induced in the reperfused myocardium and may modulate the reaction to injury. J Immunol. 2000;165:2798‐2808.
Frangogiannis NG. The role of transforming growth factor (TGF)‐beta in the infarcted myocardium. J Thorac Dis. 2017;9:S52‐S63.
Kong P, Shinde AV, Su Y, et al. Opposing actions of fibroblast and cardiomyocyte Smad3 signaling in the infarcted myocardium. Circulation. 2018;137:707‐724.
Frangogiannis NG. Transforming growth factor‐beta in myocardial disease. Nat Rev Cardiol. 2022;19:435‐455.
Shinde AV, Humeres C, Frangogiannis NG. The role of alpha‐smooth muscle actin in fibroblast‐mediated matrix contraction and remodeling. Biochim Biophys Acta. 2017;1863:298‐309.
Frangogiannis NG. The extracellular matrix in myocardial injury, repair, and remodeling. J Clin Invest. 2017;127:1600‐1612.
Hanna A, Shinde AV, Frangogiannis NG. Validation of diagnostic criteria and histopathological characterization of cardiac rupture in the mouse model of nonreperfused myocardial infarction. Am J Physiol Heart Circ Physiol. 2020;319:H948‐H964.
Fu X, Khalil H, Kanisicak O, et al. Specialized fibroblast differentiated states underlie scar formation in the infarcted mouse heart. J Clin Invest. 2018;128:2127‐2143.
Alex L, Frangogiannis NG. Pericytes in the infarcted heart. Vasc Biol. 2019;1:H23‐H31.
Gao XM, Wu QZ, Kiriazis H, et al. Microvascular leakage in acute myocardial infarction: characterization by histology, biochemistry, and magnetic resonance imaging. Am J Physiol Heart Circ Physiol. 2017;312:H1068‐H1075.
Hollander MR, de Waard GA, Konijnenberg LS, et al. Dissecting the effects of ischemia and reperfusion on the coronary microcirculation in a rat model of acute myocardial infarction. PLoS One. 2016;11:e0157233.
Trost A, Lange S, Schroedl F, et al. Brain and retinal pericytes: origin, function and role. Front Cell Neurosci. 2016;10:20.
Kottke MA, Walters TJ. Where's the leak in vascular barriers? A review. Shock. 2016;46:20‐36.
Quijada P, Park S, Zhao P, et al. Cardiac pericytes mediate the remodeling response to myocardial infarction. J Clin Invest. 2023;133:e162188.
Alex L, Tuleta I, Hernandez SC, et al. Cardiac pericytes acquire a fibrogenic phenotype and contribute to vascular maturation after myocardial infarction. Circulation. 2023;148:882‐898.
Siao CJ, Lorentz CU, Kermani P, et al. ProNGF, a cytokine induced after myocardial infarction in humans, targets pericytes to promote microvascular damage and activation. J Exp Med. 2012;209:2291‐2305.
Lee SJ, Lee CK, Kang S, et al. Angiopoietin‐2 exacerbates cardiac hypoxia and inflammation after myocardial infarction. J Clin Invest. 2018;128:5018‐5033.
Pettersson A, Nagy JA, Brown LF, et al. Heterogeneity of the angiogenic response induced in different normal adult tissues by vascular permeability factor/vascular endothelial growth factor. Lab Invest. 2000;80:99‐115.
Hellstrom M, Gerhardt H, Kalen M, et al. Lack of pericytes leads to endothelial hyperplasia and abnormal vascular morphogenesis. J Cell Biol. 2001;153:543‐553.
Nyul‐Toth A, Kozma M, Nagyoszi P, et al. Expression of pattern recognition receptors and activation of the non‐canonical inflammasome pathway in brain pericytes. Brain Behav Immun. 2017;64:220‐231.
Edelman DA, Jiang Y, Tyburski JG, Wilson RF, Steffes CP. Lipopolysaccharide activation of pericyte's toll‐like receptor‐4 regulates co‐culture permeability. Am J Surg. 2007;193:730‐735.
Stark K, Eckart A, Haidari S, et al. Capillary and arteriolar pericytes attract innate leukocytes exiting through venules and ‘instruct’ them with pattern‐recognition and motility programs. Nat Immunol. 2013;14:41‐51.
Leaf IA, Nakagawa S, Johnson BG, et al. Pericyte MyD88 and IRAK4 control inflammatory and fibrotic responses to tissue injury. J Clin Invest. 2017;127:321‐334.
Mezzaroma E, Toldo S, Farkas D, et al. The inflammasome promotes adverse cardiac remodeling following acute myocardial infarction in the mouse. Proc Natl Acad Sci USA. 2011;108:19725‐19730.
Frangogiannis NG, Mendoza LH, Lewallen M, Michael LH, Smith CW, Entman ML. Induction and suppression of interferon‐inducible protein 10 in reperfused myocardial infarcts may regulate angiogenesis. FASEB J. 2001;15:1428‐1430.
Anzai A, Choi JL, He S, et al. The infarcted myocardium solicits GM‐CSF for the detrimental oversupply of inflammatory leukocytes. J Exp Med. 2017;214:3293‐3310.
Bajpai G, Bredemeyer A, Li W, et al. Tissue resident CCR2‐ and CCR2+ cardiac macrophages differentially orchestrate monocyte recruitment and fate specification following myocardial injury. Circ Res. 2019;124:263‐278.
Proebstl D, Voisin MB, Woodfin A, et al. Pericytes support neutrophil subendothelial cell crawling and breaching of venular walls in vivo. J Exp Med. 2012;209:1219‐1234.
Allencherril J, Jneid H, Atar D, et al. Pathophysiology, diagnosis, and management of the no‐reflow phenomenon. Cardiovasc Drugs Ther. 2019;33:589‐597.
Kloner RA, Ganote CE, Jennings RB. The “no‐reflow” phenomenon after temporary coronary occlusion in the dog. J Clin Invest. 1974;54:1496‐1508.
Schwartz BG, Kloner RA. Coronary no reflow. J Mol Cell Cardiol. 2012;52:873‐882.
Kloner RA, Rude RE, Carlson N, Maroko PR, DeBoer LW, Braunwald E. Ultrastructural evidence of microvascular damage and myocardial cell injury after coronary artery occlusion: which comes first? Circulation. 1980;62:945‐952.
Rezkalla SH, Stankowski RV, Hanna J, Kloner RA. Management of no‐reflow phenomenon in the catheterization laboratory. JACC Cardiovasc Interv. 2017;10:215‐223.
O'Farrell FM, Attwell D. A role for pericytes in coronary no‐reflow. Nat Rev Cardiol. 2014;11:427‐432.
Costa MA, Paiva AE, Andreotti JP, et al. Pericytes constrict blood vessels after myocardial ischemia. J Mol Cell Cardiol. 2018;116:1‐4.
Kaul S, Methner C, Cao Z, Mishra A. Mechanisms of the “no‐reflow” phenomenon after acute myocardial infarction: potential role of pericytes. JACC Basic Transl Sci. 2023;8:204‐220.
Chen W, Saxena A, Li N, et al. Endogenous Irak‐M attenuates postinfarction remodeling through effects on macrophages and fibroblasts. Arterioscler Thromb Vasc Biol. 2012;32:2598‐2608.
Cleutjens JP, Verluyten MJ, Smiths JF, Daemen MJ. Collagen remodeling after myocardial infarction in the rat heart. Am J Pathol. 1995;147:325‐338.
Khalil H, Kanisicak O, Vagnozzi RJ, et al. Cell‐specific ablation of Hsp47 defines the collagen‐producing cells in the injured heart. JCI Insight. 2019;4:e128722.
Sava P, Ramanathan A, Dobronyi A, et al. Human pericytes adopt myofibroblast properties in the microenvironment of the IPF lung. JCI Insight. 2017;2:e96352.
Sundberg C, Ivarsson M, Gerdin B, Rubin K. Pericytes as collagen‐producing cells in excessive dermal scarring. Lab Invest. 1996;74:452‐466.
Kraler S, Balbi C, Vdovenko D, et al. Circulating GDF11 exacerbates myocardial injury in mice and associates with increased infarct size in humans. Cardiovasc Res. 2023;119:2729‐2742.
Wu X, Reboll MR, Korf‐Klingebiel M, Wollert KC. Angiogenesis after acute myocardial infarction. Cardiovasc Res. 2021;117:1257‐1273.
Li R, Chen B, Kubota A, et al. Protective effects of macrophage‐specific integrin alpha5 in myocardial infarction are associated with accentuated angiogenesis. Nat Commun. 2023;14:7555.
van Hinsbergh VW, Koolwijk P. Endothelial sprouting and angiogenesis: matrix metalloproteinases in the lead. Cardiovasc Res. 2008;78:203‐212.
Zymek P, Bujak M, Chatila K, et al. The role of platelet‐derived growth factor signaling in healing myocardial infarcts. J Am Coll Cardiol. 2006;48:2315‐2323.
Dobaczewski M, Akrivakis S, Nasser K, Michael LH, Entman ML, Frangogiannis NG. Vascular mural cells in healing canine myocardial infarcts. J Histochem Cytochem. 2004;52:1019‐1029.
Pfeffer MA, Shah AM, Borlaug BA. Heart failure with preserved ejection fraction in perspective. Circ Res. 2019;124:1598‐1617.
Braunwald E. Heart Disease. A Textbook of Cardiovascular Medicine. 4th ed. WB Saunders; 1992.
Rolle IG, Crivellari I, Zanello A, et al. Heart failure impairs the mechanotransduction properties of human cardiac pericytes. J Mol Cell Cardiol. 2021;151:15‐30.
Koenig AL, Shchukina I, Amrute J, et al. Single‐cell transcriptomics reveals cell‐type‐specific diversification in human heart failure. Nat Cardiovasc Res. 2022;1:263‐280.
Sasayama S, Ross J Jr, Franklin D, Bloor CM, Bishop S, Dilley RB. Adaptations of the left ventricle to chronic pressure overload. Circ Res. 1976;38:172‐178.
Schwartzkopff B, Frenzel H, Dieckerhoff J, et al. Morphometric investigation of human myocardium in arterial hypertension and valvular aortic stenosis. Eur Heart J. 1992;13 Suppl D:17‐23.
van Hoeven KH, Factor SM. A comparison of the pathological spectrum of hypertensive, diabetic, and hypertensive‐diabetic heart disease. Circulation. 1990;82:848‐855.
Brilla CG, Maisch B. Regulation of the structural remodelling of the myocardium: from hypertrophy to heart failure. Eur Heart J. 1994;15 Suppl D:45‐52.
Schellings MW, Pinto YM, Heymans S. Matricellular proteins in the heart: possible role during stress and remodeling. Cardiovasc Res. 2004;64:24‐31.
Frangogiannis NG. Matricellular proteins in cardiac adaptation and disease. Physiol Rev. 2012;92:635‐688.
Saucerman JJ, Tan PM, Buchholz KS, McCulloch AD, Omens JH. Mechanical regulation of gene expression in cardiac myocytes and fibroblasts. Nat Rev Cardiol. 2019;16:361‐378.
Sun M, Chen M, Dawood F, et al. Tumor necrosis factor‐alpha mediates cardiac remodeling and ventricular dysfunction after pressure overload state. Circulation. 2007;115:1398‐1407.
Khalil H, Kanisicak O, Prasad V, et al. Fibroblast‐specific TGF‐beta‐Smad2/3 signaling underlies cardiac fibrosis. J Clin Invest. 2017;127:3770‐3783.
Liu X, Burke RM, Lighthouse JK, et al. P53 regulates the extent of fibroblast proliferation and fibrosis in left ventricle pressure overload. Circ Res. 2023;133:271‐287.
Witsch T, Martinod K, Sorvillo N, Portier I, De Meyer SF, Wagner DD. Recombinant human ADAMTS13 treatment improves myocardial remodeling and functionality after pressure overload injury in mice. J Am Heart Assoc. 2018;7:e007004.
Paulus WJ, Tschope C. A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J Am Coll Cardiol. 2013;62:263‐271.
Salvador AM, Nevers T, Velazquez F, et al. Intercellular adhesion molecule 1 regulates left ventricular leukocyte infiltration, cardiac remodeling, and function in pressure overload‐induced heart failure. J Am Heart Assoc. 2016;5:e003126.
Ali SR, Ranjbarvaziri S, Talkhabi M, et al. Developmental heterogeneity of cardiac fibroblasts does not predict pathological proliferation and activation. Circ Res. 2014;115:625‐635.
Moore‐Morris T, Guimaraes‐Camboa N, Banerjee I, et al. Resident fibroblast lineages mediate pressure overload‐induced cardiac fibrosis. J Clin Invest. 2014;124:2921‐2934.
Avolio E, Mangialardi G, Slater SC, et al. Secreted protein acidic and cysteine rich matricellular protein is enriched in the bioactive fraction of the human vascular pericyte secretome. Antioxid Redox Signal. 2021;34:1151‐1164.
Peisker F, Halder M, Nagai J, et al. Mapping the cardiac vascular niche in heart failure. Nat Commun. 2022;13:3027.
Methner C, Mishra A, Golgotiu K, et al. Pericyte constriction underlies capillary derecruitment during hyperemia in the setting of arterial stenosis. Am J Physiol Heart Circ Physiol. 2019;317:H255‐H263.
McConkey HZR, Marber M, Chiribiri A, Pibarot P, Redwood SR, Prendergast BD. Coronary microcirculation in aortic stenosis. Circ Cardiovasc Interv. 2019;12:e007547.
Camici PG, Olivotto I, Rimoldi OE. The coronary circulation and blood flow in left ventricular hypertrophy. J Mol Cell Cardiol. 2012;52:857‐864.
Camici PG, Tschope C, Di Carli MF, Rimoldi O, Van Linthout S. Coronary microvascular dysfunction in hypertrophy and heart failure. Cardiovasc Res. 2020;116:806‐816.
Mohammed SF, Hussain S, Mirzoyev SA, Edwards WD, Maleszewski JJ, Redfield MM. Coronary microvascular rarefaction and myocardial fibrosis in heart failure with preserved ejection fraction. Circulation. 2015;131:550‐559.
Gilbert RE, Krum H. Heart failure in diabetes: effects of anti‐hyperglycaemic drug therapy. Lancet. 2015;385:2107‐2117.
Rubler S, Dlugash J, Yuceoglu YZ, Kumral T, Branwood AW, Grishman A. New type of cardiomyopathy associated with diabetic glomerulosclerosis. Am J Cardiol. 1972;30:595‐602.
Tuleta I, Frangogiannis NG. Fibrosis of the diabetic heart: clinical significance, molecular mechanisms, and therapeutic opportunities. Adv Drug Deliv Rev. 2021;176:113904.
Alex L, Russo I, Holoborodko V, Frangogiannis NG. Characterization of a mouse model of obesity‐related fibrotic cardiomyopathy that recapitulates features of human heart failure with preserved ejection fraction. Am J Physiol Heart Circ Physiol. 2018;315:H934‐H949.
Obokata M, Reddy YNV, Pislaru SV, Melenovsky V, Borlaug BA. Evidence supporting the existence of a distinct obese phenotype of heart failure with preserved ejection fraction. Circulation. 2017;136:6‐19.
Mangialardi G, Ferland‐McCollough D, Maselli D, et al. Bone marrow pericyte dysfunction in individuals with type 2 diabetes. Diabetologia. 2019;62:1275‐1290.
Hammes HP, Lin J, Renner O, et al. Pericytes and the pathogenesis of diabetic retinopathy. Diabetes. 2002;51:3107‐3112.
Feenstra DJ, Yego EC, Mohr S. Modes of retinal cell death in diabetic retinopathy. J Clin Exp Ophthalmol. 2013;4:298.
Romeo G, Liu WH, Asnaghi V, Kern TS, Lorenzi M. Activation of nuclear factor‐kappaB induced by diabetes and high glucose regulates a proapoptotic program in retinal pericytes. Diabetes. 2002;51:2241‐2248.
Li W, Shen S, Khatami M, Rockey JH. Stimulation of retinal capillary pericyte protein and collagen synthesis in culture by high‐glucose concentration. Diabetes. 1984;33:785‐789.
Gillies MC, Su T. High glucose inhibits retinal capillary pericyte contractility in vitro. Invest Ophthalmol Vis Sci. 1993;34:3396‐3401.
Liu Y, Zhang H, Wang S, et al. Reduced pericyte and tight junction coverage in old diabetic rats are associated with hyperglycemia‐induced cerebrovascular pericyte dysfunction. Am J Physiol Heart Circ Physiol. 2021;320:H549‐H562.
Caporali A, Meloni M, Nailor A, et al. p75(NTR)‐dependent activation of NF‐kappaB regulates microRNA‐503 transcription and pericyte‐endothelial crosstalk in diabetes after limb ischaemia. Nat Commun. 2015;6:8024.
Hinkel R, Howe A, Renner S, et al. Diabetes mellitus‐induced microvascular destabilization in the myocardium. J Am Coll Cardiol. 2017;69:131‐143.
Alex L, Tuleta I, Hanna A, Frangogiannis NG. Diabetes induces cardiac fibroblast activation, promoting a matrix‐preserving nonmyofibroblast phenotype, without stimulating pericyte to fibroblast conversion. J Am Heart Assoc. 2023;12:e027463.
Shi S, Qin M, Shen B, et al. Association of cardiac injury with mortality in hospitalized patients with COVID‐19 in Wuhan, China. JAMA Cardiol. 2020;5:802‐810.
Shi S, Qin M, Cai Y, et al. Characteristics and clinical significance of myocardial injury in patients with severe coronavirus disease 2019. Eur Heart J. 2020;41:2070‐2079.
Frangogiannis NG. The significance of COVID‐19‐associated myocardial injury: how overinterpretation of scientific findings can fuel media sensationalism and spread misinformation. Eur Heart J. 2020;41:3836‐3838.
Buja LM, Wolf DA, Zhao B, et al. The emerging spectrum of cardiopulmonary pathology of the coronavirus disease 2019 (COVID‐19): report of 3 autopsies from Houston, Texas, and review of autopsy findings from other United States cities. Cardiovasc Pathol. 2020;48:107233.
Bradley BT, Maioli H, Johnston R, et al. Histopathology and ultrastructural findings of fatal COVID‐19 infections in Washington state: a case series. Lancet. 2020;396:320‐332.
Basso C, Leone O, Rizzo S, et al. Pathological features of COVID‐19‐associated myocardial injury: a multicentre cardiovascular pathology study. Eur Heart J. 2020;41:3827‐3835.
Robinson FA, Mihealsick RP, Wagener BM, et al. Role of angiotensin‐converting enzyme 2 and pericytes in cardiac complications of COVID‐19 infection. Am J Physiol Heart Circ Physiol. 2020;319:H1059‐H1068.
Guzik TJ, Mohiddin SA, Dimarco A, et al. COVID‐19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options. Cardiovasc Res. 2020;116:1666‐1687.
Tsai EJ, Ci D, Tucker NR. Cell‐specific mechanisms in the heart of COVID‐19 patients. Circ Res. 2023;132:1290‐1301.
Brumback BD, Dmytrenko O, Robinson AN, et al. Human cardiac pericytes are susceptible to SARS‐CoV‐2 infection. JACC Basic Transl Sci. 2023;8:109‐120.
Khan AO, Reyat JS, Hill H, et al. Preferential uptake of SARS‐CoV‐2 by pericytes potentiates vascular damage and permeability in an organoid model of the microvasculature. Cardiovasc Res. 2022;118:3085‐3096.
Avolio E, Madeddu P. Discovering cardiac pericyte biology: from physiopathological mechanisms to potential therapeutic applications in ischemic heart disease. Vascul Pharmacol. 2016;86:53‐63.
Avolio E, Meloni M, Spencer HL, et al. Combined intramyocardial delivery of human pericytes and cardiac stem cells additively improves the healing of mouse infarcted hearts through stimulation of vascular and muscular repair. Circ Res. 2015;116:e81‐e94.
Cathery W, Faulkner A, Maselli D, Madeddu P. Concise Review: the regenerative journey of pericytes toward clinical translation. Stem Cells. 2018;36:1295‐1310.
Katare R, Riu F, Mitchell K, et al. Transplantation of human pericyte progenitor cells improves the repair of infarcted heart through activation of an angiogenic program involving micro‐RNA‐132. Circ Res. 2011;109:894‐906.
Alvino VV, Fernandez‐Jimenez R, Rodriguez‐Arabaolaza I, et al. Transplantation of allogeneic pericytes improves myocardial vascularization and reduces interstitial fibrosis in a swine model of reperfused acute myocardial infarction. J Am Heart Assoc. 2018;7:e006727.
Chen CW, Okada M, Proto JD, et al. Human pericytes for ischemic heart repair. Stem Cells. 2013;31:305‐316.
Avolio E, Katare R, Thomas AC, et al. Cardiac pericyte reprogramming by MEK inhibition promotes arteriologenesis and angiogenesis of the ischemic heart. J Clin Invest. 2022;132:e152308.
Alvino VV, Mohammed KAK, Gu Y, Madeddu P. Approaches for the isolation and long‐term expansion of pericytes from human and animal tissues. Front Cardiovasc Med. 2022;9:1095141.
Lee LL, Khakoo AY, Chintalgattu V. Isolation and purification of murine cardiac pericytes. J Vis Exp. 2019;(150). doi:10.3791/59571
He L, Vanlandewijck M, Raschperger E, et al. Analysis of the brain mural cell transcriptome. Sci Rep. 2016;6:35108.
Cho H, Park C, Hwang IY, et al. Rgs5 targeting leads to chronic low blood pressure and a lean body habitus. Mol Cell Biol. 2008;28:2590‐2597.
Sladojevic N, Yu B, Liao JK. Regulator of G‐protein signaling 5 maintains brain endothelial cell function in focal cerebral ischemia. J Am Heart Assoc. 2020;9:e017533.
Birbrair A, Zhang T, Wang ZM, Messi ML, Mintz A, Delbono O. Pericytes at the intersection between tissue regeneration and pathology. Clin Sci (Lond). 2015;128:81‐93.
Milner DJ, Weitzer G, Tran D, Bradley A, Capetanaki Y. Disruption of muscle architecture and myocardial degeneration in mice lacking desmin. J Cell Biol. 1996;134:1255‐1270.
Avolio E, Rodriguez‐Arabaolaza I, Spencer HL, et al. Expansion and characterization of neonatal cardiac pericytes provides a novel cellular option for tissue engineering in congenital heart disease. J Am Heart Assoc. 2015;4:e002043.
Meus MA, Hertig V, Villeneuve L, Jasmin JF, Calderone A. Nestin expressed by pre‐existing cardiomyocytes recapitulated in part an embryonic phenotype; suppressive role of p38 MAPK. J Cell Physiol. 2017;232:1717‐1727.
Hertig V, Tardif K, Meus MA, et al. Nestin expression is upregulated in the fibrotic rat heart and is localized in collagen‐expressing mesenchymal cells and interstitial CD31(+)‐ cells. PLoS One. 2017;12:e0176147.
Hui M, Tenenbaum HC. New face of an old enzyme: alkaline phosphatase may contribute to human tissue aging by inducing tissue hardening and calcification. Anat Rec. 1998;253:91‐94.
Huebener P, Abou‐Khamis T, Zymek P, et al. CD44 is critically involved in infarct healing by regulating the inflammatory and fibrotic response. J Immunol. 2008;180:2625‐2633.
Li Y, Song D, Mao L, Abraham DM, Bursac N. Lack of Thy1 defines a pathogenic fraction of cardiac fibroblasts in heart failure. Biomaterials. 2020;236:119824.
Kapur NK, Wilson S, Yunis AA, et al. Reduced endoglin activity limits cardiac fibrosis and improves survival in heart failure. Circulation. 2012;125:2728‐2738.
Tual‐Chalot S, Garcia‐Collado M, Redgrave RE, et al. Loss of endothelial endoglin promotes high‐output heart failure through peripheral arteriovenous shunting driven by VEGF signaling. Circ Res. 2020;126:243‐257.