Millions of cardiomyocytes die immediately after myocardial infarction, regardless of whether the culprit coronary artery undergoes prompt revascularization. Residual ischaemia in the peri-infarct border zone causes further cardiomyocyte damage, resulting in a progressive decline in contractile function. To date, no treatment has succeeded in increasing the vascularization of the infarcted heart. In the past decade, new approaches that can target the heart’s highly plastic perivascular niche have been proposed. The perivascular environment is populated by mesenchymal progenitor cells, fibroblasts, myofibroblasts and pericytes, which can together mount a healing response to the ischaemic damage. In the infarcted heart, pericytes have crucial roles in angiogenesis, scar formation and stabilization, and control of the inflammatory response. Persistent ischaemia and accrual of age-related risk factors can lead to pericyte depletion and dysfunction. In this Review, we describe the phenotypic changes that characterize the response of cardiac pericytes to ischaemia and the potential of pericyte-based therapy for restoring the perivascular niche after myocardial infarction. Pericyte-related therapies that can salvage the area at risk of an ischaemic injury include exogenously administered pericytes, pericyte-derived exosomes, pericyte-engineered biomaterials, and pharmacological approaches that can stimulate the differentiation of constitutively resident pericytes towards an arteriogenic phenotype. Promising preclinical results from in vitro and in vivo studies indicate that pericytes have crucial roles in the treatment of coronary artery disease and the prevention of post-ischaemic heart failure.
Cardiac pericytes interact with endothelial cells through physical and paracrine mechanisms to maintain normal vascular homeostasis.
In the infarcted heart, pericytes have crucial roles in angiogenesis, scar formation, and stabilization and control of the inflammatory response.
Persistent ischaemia and accrual of age-related risk factors can lead to pericyte depletion and dysfunction; nevertheless, some age-related cardiac defects might be treatable using pharmacotherapeutic approaches or by supplying the heart with exogenous pericytes alone or in combination with other cell types.
A greater understanding of the molecular mechanisms underlying the numerous functions of cardiac pericytes could uncover novel therapeutic solutions for coronary artery disease.
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E.A. and P.M. are supported by a Heart Research UK translational project grant (RG2697/21/23); R.K. is supported by a Smart Idea Project grant (UOOX2205); and P.C. is supported by a National Centre for the Replacement, Refinement & Reduction of Animals in Research Skills and Knowledge grant (NC/T001216/1).
The authors declare no competing interests.
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Avolio, E., Campagnolo, P., Katare, R. et al. The role of cardiac pericytes in health and disease: therapeutic targets for myocardial infarction. Nat Rev Cardiol (2023). https://doi.org/10.1038/s41569-023-00913-y