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Matrine induces apoptosis in angiotensin II‐stimulated hyperplasia of cardiac fibroblasts: effects on Bcl‐2/Bax expression and caspase‐3 activation
Author(s) -
Li Yang,
Wang Baohua,
Zhou Chenghui,
Bi Yongyi
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a973-c
Subject(s) - matrine , apoptosis , angiotensin ii , fibroblast , angiotensin ii receptor type 1 , chemistry , caspase 3 , pharmacology , renin–angiotensin system , endocrinology , in vitro , medicine , programmed cell death , receptor , biochemistry , chromatography , blood pressure
Recent studies demonstrated that matrine (an active component from Chinese traditional herb medicine)prevented cardiac remodeling in vivo and inhibited cardiac fibroblast proliferation in vitr . Matrine is reported to induce apoptosis in a series of tumor cell lines and skin fibroblasts. It’s effect on the apoptosis of cardiac fibroblast has yet to be evaluated. The present study is designed to assess the effect of matrine on angiotensin II‐induced hyperplastic growth of cardiac fibroblasts. Cardiac fibroblasts were prepared from hearts of neonatal Kunming mice by collagenase disruption. Cultured cardiac fibroblasts were either not treated, treated with 0.1 μM angiotensin II, or matrine (2.0~4.0 mM) alone, or matrine plus angiotensin II for 12~72 hours. We found that matrine significantly, dose‐ and time‐dependently inhibited angiotensin II‐induced cell proliferation. Matrine addition to the culture medium led to most cells arrested in the G1 phase of the cell cycle, the fraction of cells in S phase was markedly decreased and the cells in sub‐G1 phase was marked increased compared to control and angiotensin II alone groups. Apoptosis index in matrine treatment group was markedly increased, accompanied by a down‐regulation in Bcl‐2/Bax ratio and an up‐regulation in cleaved caspase‐3 activity. These results suggest that matrine can induce apoptosis, thereby inhibit angiotensin‐II induced hyperplasic growth of cardiac fibroblasts. The regulations of matrine on Bcl‐2/Bax expression and caspase‐3 activation may be the pro‐apoptotic mechanisms involved.