Estrogen inhibits mast cell chymase release to prevent pressure overload-induced adverse cardiac remodeling.
Estrogen regulation of myocardial chymase and chymase effects on cardiac remodeling are unknown. To test the hypothesis that estrogen prevents pressure overload-induced adverse cardiac remodeling by inhibiting mast cell (MC) chymase release, transverse aortic constriction or sham surgery was performed in 7-week-old intact and ovariectomized (OVX) rats. Three days before creating the constriction, additional groups of OVX rats began receiving 17β-estradiol, a chymase inhibitor, or a MC stabilizer. Left ventricular function, cardiomyocyte size, collagen volume fraction, MC density and degranulation, and myocardial and plasma chymase levels were assessed 18 days postsurgery. Aortic constriction resulted in ventricular hypertrophy in intact and OVX groups, whereas collagen volume fraction was increased only in OVX rats. Chymase protein content was increased by aortic constriction in the intact and OVX groups, with the magnitude of the increase being greater in OVX rats. MC density and degranulation, plasma chymase levels, and myocardial active transforming growth factor-β1 levels were increased by aortic constriction only in OVX rats. Estrogen replacement markedly attenuated the constriction-increased myocardial chymase, MC density and degranulation, plasma chymase, and myocardial active transforming growth factor-β1, as well as prevented ventricular hypertrophy and increased collagen volume fraction. Chymostatin attenuated the aortic constriction-induced ventricular hypertrophy and collagen volume fraction in the OVX rats similar to that achieved by estrogen replacement. Nedocromil yielded similar effects, except for the reduction of chymase content. We conclude that the estrogen-inhibited release of MC chymase is responsible for the cardioprotection against transverse aortic constriction-induced adverse cardiac remodeling.
From the Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia.
Jianping
J
Li
From the Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia.
Shaiban
S
Jubair
From the Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia. joseph.janicki@uscmed.sc.edu.
Joseph S
JS
Janicki
D000818:Animals; D002312:Cardiomyopathy, Hypertrophic / Q000150:complications; D015550:Cell Degranulation / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D053818:Chymases / Q000378:metabolism*; D003094:Collagen / Q000032:analysis; D004958:Estradiol / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D005260:Female; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000517:prevention & control*; D008407:Mast Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D009206:Myocardium / Q000201:enzymology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D017835:Nedocromil / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000517:prevention & control; D020257:Ventricular Remodeling / Q000187:drug effects*
D009842:Oligopeptides; D053773:Transforming Growth Factor beta1; D017835:Nedocromil; D004958:Estradiol; D003094:Collagen; C002101:chymostatin; D053818:Chymases
cardiac remodeling; chymase; estrogen; mast cell