| Background and Objective: Left ventricular (LV) remodeling after myocardial infarction (MI) contributes significantly to LV dilation, dysfunction and death. Mechanism of LV remodeling for disability and death has received a great deal of attention.In contrast, remodeling of the extracellular collagen matrix plays a major role in left remodeling,it has received little attention.As well, A host of clinical trials showed that angiotensin-converting enzyme (ACE) inhibitor and angiotensin Ⅱ(AngⅡ) type 1 (AT1) receptor blockers (ARBs) can improve outcome in survivors of MI. However the antifibrotic action of ACEI and ARBs on collagen in the infarct zone and noninfarct zone remain unreconciled with the benefits. At present some studies think that activation of RAAS for long-time is the one of most important factor in local cardiac tissue during the development of heart remodeling and failure after myocardial infarction. AngⅡ is the one of principal members in this system, and it is the main functional molecular. It will switch and accelar in the progress of collagen synthesis and ventricle remodeling. AngⅡ can bind to specific receptor AT1 or AT2 of myocardium by autocrine and (or) paracrine type, then affect cardiac fibrosis and collagen remodeling through multiple signal-transduction pathways. Inhibiting AngⅡ synthesis in myocardium is the main method that inhibit collagen and ventricle remodeling after MI. But some investigations demonstrate the efficiency of ACEI and ARB whose roles inhibit RAAS will weaken or extinction . It will gives clue to that the development of ventricular remodeling and heart failure can not rely on RAAS of the patiens perhapsly when in some degrees of ventricular remodeling. So there is important significance if we explore the molecular mechanism of myocardium collagen and ventricular remodeling after MI. As well, some studies also have demonstrated that AngⅡ can activate extracellular signal-regulated kinase (ERK, ERK1/ERK2 is the principle member) which is one of family members of mitogen activation protein kinase(MAPK) and regulates gene expression after MI, then leads to cell proliferation and all kinds of protein synthsis, so Ang Ⅱ acts as key role in many factor leading to remodeling and failure. Meanwhile, the activity and expression of ERK and CTGF is the same phenomenon in the procession of interstitial remodeling after myocardial infarction. Super-expression of CTGF in long-term could facilitate the development of myocardial fibrosis. In this study ,we were to access the expression of AngⅡ,ERK1/ERK2 and CTGF pathway on cardiac remodeling, to explore the effect and molecular mechanisms of Captopril and Valsartan on cardiac remodeling after myocardial infarction. The aim was to provide experimental data for therapy of heart failure after myocardial infarction and clinical application of Captopril or Valsartan. Method: MI models was maded in SD rats by ligation of the left anterior descending coronary artery .Rats with extensive MI were randomized to treat with placebo,Captopril or Valsartan(100mg/kg body per day or 15mg/kg body per day) as via gavage for 8 weeks starting on the 3th post-operation day . There were four groups: Sham group (n=10), MI group (n=10),Captopril group(Cap group n=9)and Valsartan group(Val group n=10).Infarcted size, left and right ventricular weights, index of weight, cardiac hydroxyproline and collagen content of four groups wererecorded after 8 weeks. The gene expression of ERK1/ERK2 and CTGF were detected by RT-PCR. The expression of AngⅡ﹑ERK1/ERK2 and CTGF protein were detected by immunohistochemistry. Results: (1)Placebo-treated infracted rats (MI group) developed significant increase in left ventricular weight or weight index, com-pared with Sham group (p<0.05), in Cap group rats, a significant reduction of left ventricular weight index was founded (p<0.05 versus MI group),while in Val group rats, there was no significantly difference (p>0.05); Right ventricular weight or weight index has no significantly increase (p>0.05). (2) In non-infar...
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