0316 : Vascular smooth muscle mineralocorticoid receptor contributes to coronary and left ventricular dysfunction after myocardial infarction

Aims Because mineralocorticoid receptor (MR) antagonists have shown efficacy in slowing down the progression of heart failure after myocardial infarction (MI), there is interest to elucidate the cell-specific involvement of MR. Indeed, the role of MR in vascular smooth muscle cells (VSMC) in heart failure, especially its impact on coronary circulation, has never been investigated. Methods and Results Two months after MI, mice lacking the MR specifically in VSMC (MI-MRSMKO) and mice treated with the MR antagonist finerenone (MI-fine) had better coronary function than control (MI-CTL), as assessed by acetylcholine-induced relaxation of isolated arteries (relaxation %: MI-CTL: 36±5, MI-MRSMKO: 54±3, MI-fine: 76±4; P Conclusion After MI, VSMC-specific MR invalidation benefits LV dysfunction, likely through improvement of coronary reserve and of coronary endothelial function, demonstrating for the first time the deleterious role of smooth muscle MR activation in heart failure. Furthermore, systemic MR blockade by finerenone confers additional functional improvements.