Cardiac pericytes may contribute to heart disease

Abstract

Cardiovascular diseases which are the leading cause of death worldwide are promoted by well-known risk factors that include high blood pressure, age, sex, diabetes and/or obesity. Pericytes are mural cells wrapped around microvessels in many organs. They are mostly described as essential for microvascular integrity in the brain and retina. While the detrimental effects of cardiovascular risk factors on endothelial cells have been extensively studied, little is known about their impact on the biology of pericytes, especially in the heart. To determine how cardiac pericytes are modified by some cardiovascular risk factors. To do so, we used mice that were exposed to a high-fat diet (HFD) only to recapitulate obesity, to a HFD together with low dose-streptozotocin injections to mimic type 2 diabetes or to a HFD and L-NAME to recapitulate obesity with a mild hypertension. Mice were sacrificed 3 or 6 months after establishing these risk factors for histological and gene expression analyses. In mice exposed to the HFD + L-NAME regimen for 3 months, the percentage of capillaries covered by pericytes was not modified. However their phenotype appeared to be modified. Indeed, we isolated pericytes (CD31–, CD146+ cells) in the heart of both HFD L-NAME fed mice and control mice using magnetic beads and performed a bulk RNA-sequencing analysis on these cells which identified 3 genes of which the expression was significantly different in the 2 groups. In particular, Angiopoietin-like 4 mRNA expression was increased in the pericytes of HFD + L-NAME fed mice. This protein plays an important role in the regulation of lipid metabolism which makes it attractive to explore. In mice exposed to either HFD alone of HFD + streptozotocin for 6 months, the percentage of capillaries covered by pericytes was significantly diminished suggesting pericyte death. Cardiovascular risk factors, such as obesity and diabetes, may change the phenotype and/or the number of pericytes in the heart suggesting that these cells, known to be critical for microvascular integrity, could contribute to the onset of cardiac diseases.