The role of cardiac pericytes in health and disease: therapeutic targets for myocardial infarction

Millions of cardiomyocytes die immediately after a myocardial infarction event, 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 enhancing the infarcted heart’s vascularization. Therefore, new approaches that can target the heart's highly plastic perivascular niche are needed. This environment is populated by mesenchymal progenitor cells, fibroblasts, myofibroblasts and pericytes, which can natively mount a healing response to the ischaemic damage although this mechanism may be compromised by aging and risk factors. In this Review, we illustrate 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 a myocardial infarction. Treatments for salvaging of the area at risk of ischaemic injury include exogenously administered pericytes, pericyte-derived exosomes, pericyte-engineered biomaterials, and pharmacological approaches stimulating the differentiation of constitutively resident pericytes toward an arteriogenic phenotype. Promising preclinical results from in vitro and in vivo studies indicate that pericytes have a crucial role in the treatment of coronary artery disease and the prevention of post-ischaemic heart failure.