Abstract | BACKGROUND: METHODS: MI was induced by ligating the left anterior descending coronary artery in rats. Twenty-four hours after ligation, the survived rats were randomly divided into five groups and treated for 8 weeks: placebo group, ACEI group (benazepril 10 mg.kg(-1).d(-1)), ARB group (irbesartan 50 mg.kg(-1).d(-1)), ACEI + ARB group ( benazepril 10 mg.kg(-1).d(-1) + irbesartan 50 mg.kg(-1).d(-1)) and control group ( sham-operated rats). After 8 weeks, we examined the following indexes: the ratio of ventricular weight to body weight (VW/BW), left ventricular end diastolic dimension (LVDd), ejection fraction (EF), fractional shortening (FS), ratio of E-wave to A-wave velocity, collagen of noninfarcted zone, the mRNA expression of TGFbeta(1), Smad 2, and Smad 3 by RT-PCR in noninfarcted zone, the protein expression of Smad 2 and Smad 3 in noninfarcted zone by Western blot. RESULTS: VW/BW significantly increased in the placebo groups compared with that in the control group (P < 0.01). This increase was limited in ACEI, ARB, and combined groups (P < 0.01 compared with placebo group). There was no significant difference among the three actively treated groups. Collagen was increased in placebo group (5.68 +/- 0.5)% compared with that in control group (P < 0.01). ACEI, ARB and combined treatment attenuated this increase of collagen [(4.3 +/- 0.5)%, (3.5 +/- 0.5)%, (3.2 +/- 0.4)%] in comparison with that in placebo group (P < 0.01 respectively). Combined treatment showed more significant effect on collagen deposition. EF and FS significantly decreased, LVDd and E/A significantly increased in placebo group compared with that in control group (P < 0.01 respectively). ACEI, ARB and combined treatment ameliorated these indexes (P < 0.01 compared with placebo group). The mRNA expression of TGFbeta(1), Smad 2, and Smad 3 (0.700 +/- 0.045, 0.959 +/- 0.037 and 0.850 +/- 0.051) increased in placebo group compared with that in control group (P < 0.01). ACEI, ARB and combined treatment normalized the increase (P < 0.01). Furthermore, ARB and combined treatment proved to be more effective in decreasing TGF beta(1) and Smad mRNA expression than ACEI treatment (P < 0.01). The expression of Smad 2 and Smad 3 protein increased in placebo group compared with that in control group (P < 0.01). ACEI, ARB and combined treatment normalized the increase (P < 0.01). Furthermore, ARB and combined treatment proved to be more effective than ACEI alone (P < 0.01). CONCLUSIONS: TGFbeta(1)-Smads signal activation is correlated with ventricular remodeling following MI. ACEI and ARB treatment prevents ventricular remodeling by inhibiting expression of Smad 2 and Smad 3. ARB and combined treatment are more effective than ACEI alone.
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Authors | Rui-ying Zhang, Lan-feng Wang, Lei Zhang, Xiang-ning Meng, Shao-jun Li, Wu-ru Wang |
Journal | Chinese medical journal
(Chin Med J (Engl))
Vol. 119
Issue 8
Pg. 649-55
(Apr 20 2006)
ISSN: 0366-6999 [Print] China |
PMID | 16635409
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Angiotensin II Type 1 Receptor Blockers
- Angiotensin-Converting Enzyme Inhibitors
- Smad2 Protein
- Smad2 protein, rat
- Smad3 Protein
- Smad3 protein, rat
- Tgfb1 protein, rat
- Transforming Growth Factor beta
- Transforming Growth Factor beta1
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Topics |
- Angiotensin II Type 1 Receptor Blockers
(administration & dosage, therapeutic use)
- Angiotensin-Converting Enzyme Inhibitors
(administration & dosage, therapeutic use)
- Animals
- Drug Therapy, Combination
- Echocardiography
- Male
- Myocardial Infarction
(drug therapy)
- Rats
- Rats, Wistar
- Smad2 Protein
(analysis, genetics)
- Smad3 Protein
(analysis, genetics)
- Transforming Growth Factor beta
(genetics)
- Transforming Growth Factor beta1
- Ventricular Remodeling
(drug effects)
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