Aldosterone-synthase overexpression in heart: a tool to explore aldosterone's effects.
Clinical observations indicate that elevated aldosterone impairs cardiovascular function. The mechanisms, however, are not totally understood although total and cardiovascular mortality are decreased by aldosterone antagonists. Experimentally, increased plasma aldosterone induces pericoronary inflammation and cardiac fibrosis. Our laboratory has discovered that aldosterone is synthesized in the rat heart, and has demonstrated that this cardiac aldosterone is involved in post-infarction cardiac remodeling. In man, activated cardiac aldosterone production has been described in patients with heart failure. In transgenic mice that overexpress aldosterone-synthase in the heart, we observe a normal cardiac function but a major coronary dysfunction, more pronounced in males. These observations converge to a potential physiological and pathological relevance of this system. Beneficial effects of anti-aldosterone treatment in heart failure may thus be secondary in part to blockade of cardiac aldosterone action.
Heymes
C
C
IFR Circulation, INSERM U527, Hopital Lariboisiere, Université Paris 7, 41 Boulevard de la Chapelle, 75475 Paris cedex 10, France.
Garnier
A
A
Fuchs
S
S
Bendall
J K
JK
Nehme
J
J
Ambroisine
M L
ML
Robidel
E
E
Swynghedauw
B
B
Milliez
P
P
Delcayre
C
C
D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D003327:Coronary Disease / Q000235:genetics / Q000503:physiopathology; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D012737:Sex Factors; D020257:Ventricular Remodeling / Q000502:physiology
D000451:Mineralocorticoid Receptor Antagonists; D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2