Chymase inhibition reduces the progression to heart failure after autoimmune myocarditis in rats.

Chymase inhibition reduces the progression to heart failure after autoimmune myocarditis in rats. Research Abstract Details 

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Chymase inhibition reduces the progression to heart failure after autoimmune myocarditis in rats. Abstract Text:

Suresh S Palaniyandi,Yusuke Nagai,Kenichi Watanabe,Meilei Ma,Punniyakoti T Veeraveedu,Paras Prakash,Fadia A Kamal,Yuichi Abe,Ken'ichi Yamaguchi,Hitoshi Tachikawa,Makoto Kodama,Yoshifusa Aizawa,

Chymase has been known as a local angiotensin II-generating enzyme in the cardiovascular system in dogs, monkeys, hamsters, and humans; however, recently it was reported that chymase also has various other functions. Therefore, we decided to examine whether the inhibition of chymase improves disease conditions associated with the pathophysiology of dilated cardiomyopathy in rats and its possible mechanism of action as rat chymase is unable to produce angiotensin II. We examined the effect of TY-51469, a novel chymase inhibitor (0.1 mg/kg/day [group CYI-0.1, n = 15] and 1 mg/kg/day [group CYI-1, n = 15]), in myosin-immunized postmyocarditis rats. Another group of myosin-immunized rats was treated with vehicle (group V, n = 15). Age-matched normal rats without immunization (group N, n = 10) were also included in the study. After 4 weeks of treatment, we evaluated cardiac function; area of fibrosis; fibrogenesis; levels of transforming growth factor (TGF)-beta1 and collagen III; hypertrophy and its marker, atrial natriuretic peptide (ANP); and mast cell activity. Survival rate and myocardial functions improved dose-dependently with chymase inhibitor treatment after myosin immunization. A reduction in the percent area of myocardial fibrosis, fibrogenesis, myocardial hypertrophy, and mast cell activity along with a reduction in TGF-beta1, collagen III, and ANP levels in the myocardium were noted in postmyocarditis rats that received chymase inhibitor treatment. The treatment also decreased myocardial aldosterone synthase levels in those animals. Inhibition of chymase reduces the pathogenesis of postmyocarditis dilated cardiomyopathy and progression to heart failure by preventing the pathological remodeling and residual inflammation in rats.

Chymase inhibition reduces the progression to heart failure after autoimmune myocarditis in rats. Publishing Authors By Initials

SS Palaniyandi,Y Nagai,K Watanabe,M Ma,PT Veeraveedu,P Prakash,FA Kamal,Y Abe,K Yamaguchi,H Tachikawa,M Kodama,Y Aizawa,

For similar peptides: intercellular signaling peptides and proteins: cytokines: transforming growth factor beta: transforming growth factor beta1 research abstracts see: peptides: intercellular signaling peptides and proteins: cytokines: transforming growth factor beta: transforming growth factor beta1 research

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Chymase inhibition reduces the progression to heart failure after autoimmune myocarditis in rats. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Experimental biology and medicine (Maywood, N.J.)

VOLUME: 232

Page Numbers: 1213-21

Journal Abbreviation: Exp. Biol. Med. (Maywood)

ISSN: 1535-3702

DAY: 27

MONTH: Oct

YEAR: 2007

Chymase inhibition reduces the progression to heart failure after autoimmune myocarditis in rats. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 100973463

Chymase inhibition reduces the progression to heart failure after autoimmune myocarditis in rats. Keywords Mesh Terms:

KEYWORDS: Transforming Growth Factor beta1

MESH TERMS: metabolism

Chemical & Substance for Abstract: Chymase inhibition reduces the progression to heart failure after autoimmune myocarditis in rats. Information

Substance Name: Chymases

Registry Number: EC 3.4.21.39

Grant and Affiliation Information for Chymase inhibition reduces the progression to heart failure after autoimmune myocarditis in rats.

AFFILIATION: Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata City, 956-8603, Japan.

Country: United States

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MEDLINETA: Exp Biol Med (Maywood)

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