0542 : Vascular smooth muscle mineralocorticoid receptor contributes to coronary and left ventricular dysfunction after myocardial infarction

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• 作者：Alexandre Gueret¹ ; Najah Harouki¹ ; Julie Favre¹ ; Guillaume Galmiche² ; Lionel Nicol¹ ; Jean-Paul Henry¹ ; Christian Thuillez¹ ; Vincent Richard¹ ; Peter Kolkhof³ ; Paul Mulder⁴ ; Antoine Ouvrard-Pascaud⁴ ; ^{antoine.ouvrard-pascaud@univ-rouen.fr" class="auth_mail" title="E-mail the corresponding author} ; Fré ; dé ; ric Jaisser²
• 刊名：Archives of Cardiovascular Diseases Supplements
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：8
• 期：3
• 页码：223
• 全文大小：50 K

文摘

Mineralocorticoid receptor (MR) antagonists slow down the progression of heart failure after myocardial infarction (MI), but the cell-specific role of MR in these benefits is unclear. In the present study, the role of MR expressed in vascular smooth muscle cells (VSMC) was investigated. Two months after coronary artery ligation causing MI, mice with VSMC-specific MR deletion (MI-MRSMKO) and mice treated with the MR antagonist finerenone (MIfine) had improved left ventricular (LV) compliance and elastance when compared to infarcted control mice (MI-CTL), as well as reduced interstitial fibrosis. Importantly, the coronary reserve assessed by magnetic resonance imaging was preserved (difference in myocardial perfusion before and after induction of vasodilatation, ml/mg/min: MI-CTL: 1.1±0.5, NS; MIMRSMKO: 4.6±1.6, P<0.05; MI-fine: 3.6±0.7, P<0.01). The endothelial function, tested on isolated septal coronary arteries by analyzing the acetylcholineinduced NO-dependent relaxation, was also improved by MR deletion in VSMC or by finerenone treatment (relaxation %: MI-CTL: 36±5, MIMRSMKO: 54±3 and MI-fine: 76±4; P<0.05). Such impairment of the coronary endothelial function upon MI involved an oxidative-stress that was reduced when MR was deleted in VSMC or by finerenone treatment. Moreover, short-term incubation of coronary arteries isolated from non-infarcted animals with low dose angiotensin-II (10-9mol/L) induced oxidative-stress and impaired acetylcholine-induced relaxation in CTL but neither in MRSMKO nor in mice pre-treated with finerenone.

In conclusion, deletion of MR in VSMC improved LV dysfunction after MI, likely through maintenance of the coronary reserve and improvement of coronary endothelial function. MR blockage by finerenone had similar effects.

The author hereby declares no conflict of interest