| Objective1. Inflammation plays a pathogenic role in the progression of chronic heart failure (CHF). Several reports have demonstrated enhanced plasma levels of inflammatory cytokines in CHF patients. Although much attention has been paid to TNF-a and IL-6, few studies have examined these mediators in circulating leukocytes. Our knowledge about other members of the cytokines network is limited. The present study was designed to investigate the gene expression profiles in peripheral blood mononuclear cells (PBMC) from patients with CHF and healthy controls using a gene array, and to identify the gene expression of cytotokine network and related mediators in CHF.2. Tumor Necrosis Factor- a plays a pathogenic role in the progression of cardiac remodeling and dysfunction. The MMPs are a family of enzymes which contribute to extracelullar matrix degradation in the progression of cardiac remodeling. It has been shown how cardiac MMPs activities change after myocardial infarction. However, there have been controversies over the change of the MMPs activities, and few studies reported the time course of TNF a expression and relationship with MMPs activities during the progression of left ventricular remodeling. The present study was intended to clarify the change of cardiac TNF- a expression and matrix metalloproteinases activities, and observe their relation with ventricular remodeling and cardiac function during the progression of left ventricular remodeling in an experimental model of rat myocardial infarction.3. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, statins, has beenshown to attenuate ischemic-reperfusion injury, inhibit the expression of proinflammatory cytokines gene from PBMC in patients with CHF, reduce the expression of MMPs in vascular endothelial cells, downregulate ATI receptors in vascular smooth muscle cells and have anti-inflammatory and other cardiovascular protective effects. However, little is known about the effects of statins on left ventricular remodeling and failure post MI, and it is unknown whether the combination of ACE inhibitors and statins exert additive or synergistic effects. The aim of this study was to compare the effects of statins , ACE inhibitors and their combination on ventricular remodeling , cardiac function , TNF- a expression, and MMPs activities after myocardial infarction in rats. Methods1. Eight patients with CHF and 8 gender and age matched healthy controls were enrolled in this study. Anticoagulant blood samples from healthy controls and CHF patients were collected. PBMC were isolated. Total RNA was extracted from PBMC. Two cDNA probes for CHF and healthy controls were synthesized from total RNA by in vitro reverse transcriptional reaction and labeled with Cy5 and Cy3 respectively. Two probes were simultaneous hybridized with a gene array (the above mentioned). The hybridization signals were obtained with laser scanner and analyzed with ImaGene 3.0 software.2. 45 male Sprague Dawley (SD) rats were developed into acute myocardial infarction by ligation of the anterior descending coronary artery and divided randomly into five groups of 1, 7, 14, 28, and 42 days after infarction. 45 rats were randomized into five sham-operated groups corresponding to five infracted groups. Heart function and left ventricular remodeling were confirmed by echocardiography and hemodynamic measurements. The relative expression of TNF- a mRNA was assessed by the technique of reverse transcription-polymerase chain reaction (RT-PCR). MMPs activities were assessed by Zymography.3. Fifty male SD rats were developed into acute myocardial infarction and divided randomly into myocardial infarction(MI) control, ACE inhibitor fosinopril(10 mg/kg/d), statins pravastatin (20 mg/kg/d) and a combination of the above drugsgroup respectively. Ten rats were selected randomly as Sham-operated group. Six weeks after treatment with the drugs by gastric gavage, heart weight (HW)/body weight(BW) ratio was determined. The expression o...
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