Beggah Ahmed T, Escoubet Brigitte, Puttini Stefania, Cailmail Stephane, Delage Vanessa, Ouvrard-Pascaud Antoine, Bocchi Brigitte, Peuchmaur Michel, Delcayre Claude, Farman Nicolette, Jaisser Frederic
Institut National de la Santé et de la Recherche Médicale U478, Hôpital Bichat-Claude Bernard, AP-HP, Federative Institute of Research 02, 75870 Paris, France.
Proc Natl Acad Sci U S A. 2002 May 14;99(10):7160-5. doi: 10.1073/pnas.102673599. Epub 2002 May 7.
Cardiac failure is a common feature in the evolution of cardiac disease. Among the determinants of cardiac failure, the renin-angiotensin-aldosterone system has a central role, and antagonism of the mineralocorticoid receptor (MR) has been proposed as a therapeutic strategy. In this study, we questioned the role of the MR, not of aldosterone, on heart function, using an inducible and cardiac-specific transgenic mouse model. We have generated a conditional knock-down model by expressing solely in the heart an antisense mRNA directed against the murine MR, a transcription factor with unknown targets in cardiomyocytes. Within 2-3 mo, mice developed severe heart failure and cardiac fibrosis in the absence of hypertension or chronic hyperaldosteronism. Moreover, cardiac failure and fibrosis were fully reversible when MR antisense mRNA expression was subsequently suppressed.
心力衰竭是心脏疾病发展过程中的一个常见特征。在心力衰竭的决定因素中，肾素-血管紧张素-醛固酮系统起着核心作用，拮抗盐皮质激素受体（MR）已被提出作为一种治疗策略。在本研究中，我们使用可诱导的心脏特异性转基因小鼠模型，探究了MR而非醛固酮对心脏功能的作用。我们通过仅在心脏中表达针对小鼠MR的反义mRNA，构建了一个条件性敲低模型，MR是一种在心肌细胞中靶标未知的转录因子。在2至3个月内，小鼠在无高血压或慢性醛固酮增多症的情况下出现了严重的心力衰竭和心脏纤维化。此外，当随后抑制MR反义mRNA表达时，心力衰竭和纤维化完全可逆。
