Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0264733 (ventricular dilatation)
 2,163 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to compare the angiotensin II type 1 receptor antagonist candesartan cilexitil (candesartan) and the angiotensin-converting enzyme inhibitor cilazapril on cardiac function, assessed by Doppler echocardiography and cardiac gene expression associated with cardiac remodeling, in rats with myocardial infarction. Candesartan or cilazapril was administered after myocardial infarction. At 1 and 4 weeks after myocardial infarction, cardiac function and mRNA expression in noninfarcted myocardium were analyzed. Candesartan and cilazapril equally prevented increases in hypertrophy in noninfarcted myocardium, left ventricular dilatation, and ejection fraction at 4 weeks. The E-wave/A-wave velocity ratio and the rate of E-wave deceleration, measures of diastolic function, increased to 9.2+/-0.6 and 26.3+/-2. 6 m/s2 at 1 week after myocardial infarction. Candesartan and cilazapril, administered at a dose of 1 mg/kg per day, prevented increases in E-wave/A-wave velocity ratio and E-wave deceleration at 1 and 4 weeks. Candesartan and cilazapril significantly suppressed increased mRNA expression of beta-myosin heavy chain, alpha-skeletal actin, and atrial natriuretic peptide in noninfarcted ventricle at 1 and 4 weeks and expression of collagen I and III at 4 weeks to a similar extent. When given at a dose of 10 mg/kg per day, both candesartan and cilazapril prevented cardiac dysfunction and gene expression to the same extent as when given at 1 mg/kg per day. In conclusion, Doppler echocardiography showed that candesartan and cilazapril equally improved systolic and diastolic function and that ventricular remodeling accompanied modulation of cardiac gene expression.
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PMID:Effects of candesartan and cilazapril on rats with myocardial infarction assessed by echocardiography. 1020 31

The cardiovascular interstitial space is largely composed of type I and III fibrillar collagens. Tissue structure, form and function are determined not only by the collagen content but also by the ratio of different collagens to each other. Matrix metalloproteinases are members of a family of secreted and membrane-bound enzymes that are capable of degrading highly proteolytic resistant fibrillar type I and III collagens. Collagen tissue content is determined by balanced collagen synthesis and degradation. MMP activity and adverse tissue remodeling have been identified in coronary plaques in unstable angina. It has also been linked with the progression of aortic aneurysms and with left ventricular dilatation in congestive heart failure in patients with ischemic and non-ischemic cardiomyopathy. The role of MMPs in these cardiovascular diseases and possible therapeutic options are the focus of this review.
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PMID:[Significance of matrix metalloproteinases in cardiovascular diseases]. 1109 46

We previously reported an approximately 50% incidence of rats with symptoms of congestive heart failure (CHF) at 8 wk postinfrarenal aorto-caval fistula. However, it was not clear whether compensatory ventricular remodeling could continue beyond 8 wk or whether the remaining animals would have developed CHF or died. Therefore, the intent of this study was to complete the characterization of this model of sustained volume overload by determining the morbidity and mortality and the temporal response of left ventricular (LV) remodeling and function beyond 8 wk. The findings demonstrate an upper limit to LV hypertrophy and substantial increases in LV volume and compliance, matrix metalloproteinase activity, and collagen volume fraction associated with the development of CHF. There was an 80% incidence of morbidity and mortality following 21 wk of chronic volume overload. These findings indicate that the development of CHF is triggered by marked ventricular dilatation and increased compliance occurring once the myocardial hypertrophic response is exhausted.
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PMID:Contribution of ventricular remodeling to pathogenesis of heart failure in rats. 1115 66

Progressive ventricular dilatation commonly accompanies the transition to overt failure in chronically overloaded hearts; however, only recently have studies begun to elucidate underlying molecular alterations. In particular, the potential role of altered myocardial expression of the procollagenase gene in this process has not previously been examined. Biventricular hypertrophy and dilatation were produced in rats by creating an abdominal aortocaval fistula. The time courses of changes in expression of collagen I and III genes and of the procollagenase gene (matrix metalloproteinase-1, MMP-1) were assessed by Northern blot hybridization. Expression of all three genes increased promptly; however, collagenase gene expression peaked much earlier (8 h) than did expression of either of the collagen genes (7 days), and all returned to baseline levels by 45 days. These data corroborate earlier reports of increased collagen gene expression in this model, but more importantly, they provide the first evidence of concurrent activation of collagenase gene expression, suggesting that enhancement of collagen degradation may be a prerequisite for structural cardiac dilatation.
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PMID:Changes in collagenase and collagen gene expression after induction of aortocaval fistula in rats. 1140 87

Left ventricular remodeling is the process by which ventricular size, shape, and function are regulated by mechanical, neurohormonal, and genetic factors. Remodeling may be physiological and adaptive during normal growth or pathological due to myocardial infarction, cardiomyopathy, hypertension, or valvular heart disease. Postinfarction remodeling has been divided into an early phase within 72 hours and a late phase beyond 72 hours. The early phase involves expansion of the infarct zone, which may result in early ventricular rupture or aneurysm formation. Late remodeling involves the left ventricle globally and is associated with time-dependent dilatation, the distortion of ventricular shape, and mural hypertrophy. Hypertrophy and collagen degradation are adaptive responses during postinfarction remodeling. Myocardial repair is triggered by cytokines released from injured myocytes. Ventricular remodeling is influenced most by infarct artery patency. Once infarct evolution has occurred, pharmacological intervention, like ACE inhibition and beta-adrenoreceptor blocking agents, may minimize infarct expansion and ventricular dilatation and improve the long-term prognosis.
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PMID:[Pathophysiology and therapeutic aspects of left ventricular "remodeling" in the post-infarct phase]. 1177 72

The effect of ACE inhibition after myocardial infarction (MI) on MI healing and remodeling in the presence of hypertension is not exactly known. Therefore, the effect of quinapril on scar formation, remodeling and hemodynamics was studied in spontaneously hypertensive rats (SHR). Nine weeks after moderate and large MI, left ventricular end-diastolic pressure (LVEDP) and passive pressure-volume relations were similar in 28-week-old hypertensive and normotensive rats. Chronic therapy with quinapril (6 mg/kg/day, started 30 min post-MI) reduced LVEDP and LV to body weight ratio, yet did not affect pressure-volume relations. Quinapril increased MI size and reduced the content and brightness of collagen fibers in the scar examined by polarized light microscopy. In conclusion, ventricular dilatation after MI was not accelerated in SHR, probably due to LV hypertrophy. Quinapril produced beneficial hemodynamic effects similar to that observed in the normotensive rat model. The significance and timing of ACE inhibitor-induced impairment of scar formation need further evaluation.
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PMID:Ventricular remodeling after myocardial infarction and effects of ACE inhibition on hemodynamics and scar formation in SHR. 1193 99

The most common etiologies for mitral regurgitation (MR) include mitral valve prolapse syndrome, coronary artery disease, infective endocarditis, rheumatic heart disease, collagen vascular disease, and, recently, anoretic drugs have also been reported to cause MR. In chronic severe MR, forward cardiac output is maintained for the development of afterload reduction with increase in compensatory left ventricular (LV) end-diastolic volume and LV ejection fraction. It is well established that some patients with asymptomatic mitral regurgitation develop irreversible contractile dysfunction of the LV, which is often masked by the afterload-reducing effect of the regurgitant flow; cardiologist have to use some variables, like LV chamber elastance, LV End-Systolic dimensions and volumes, left atrial area combined with ejection fraction, in their clinical evaluations tube able to predict surgery mortality. Careful and periodic evaluation of left ventricular function and size is essential to optimize the timing of surgical intervention in these patients. After symptoms occur, outcome is improved with surgical interventions compared to medical therapy, with a reported survival of only 45% at 5 years without surgical intervention. Vasodilators, diuretics, and recently, angiotensin receptor antagonists have been used in MR medical therapy. Long-term carvedilol therapy in patients with chronic heart failure may prevent or partially reverse progressive left ventricular dilatation. Concomitant by, it has been associated with recovery of diastolic reserve and a decrease in mitral regurgitation.
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PMID:[Heart failure and pure mitral failure. Prognostic impact and its best treatment]. 1200 70

Mast cells contain proteases capable of activating matrix metalloproteinases (MMPs). However, given the relatively low density of mast cells in the myocardium (i.e., 1.5-5.3 cells/mm(2)), it is unknown whether these enzymes are present in sufficient quantities in the normal heart to mediate MMP activation. Accordingly, this study sought to determine whether chemically induced degranulation of cardiac mast cells (with compound 48/80) would have an effect in isolated, blood-perfused, functioning rat hearts. Mast cell degranulation produced a 15% increase in histamine levels present in the coronary efflux, a significant increase in myocardial water (i.e., edema) relative to normal values (80.1 +/- 3.4% vs. 77.4 +/- 1.08%, P < or = 0.03), a substantial activation of MMP-2 (126% increase relative to controls, P < or = 0.02), and a marked decrease in myocardial collagen volume fraction (0.46 +/- 0.10% vs. 0.97 +/- 0.33%, P < or = 0.001). Furthermore, although an increase in ventricular stiffness was expected due to the extent of edema resulting from mast cell degranulation, modest ventricular dilatation was observed. These findings clearly demonstrate that the number of mast cells present in normal hearts is sufficient to mediate activation of MMPs and produce extracellular matrix degradation, thereby potentially causing subsequent ventricular dilatation.
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PMID:Cardiac mast cell-mediated activation of gelatinase and alteration of ventricular diastolic function. 1200 23

In the heart, collagens are the major extracellular matrix (ECM) protein. The fibrillar collagens of the heart surround and interconnect myocytes and muscle fibers to provide for muscle fiber and myocyte alignment which imparts mechanical support to the myocardium and governs tissue stiffness. Loss of collagen fibrils and struts are said to lead to myocyte slippage, ventricular dilation, and progressive contractile dysfunction. Failed human hearts examined either at autopsy or explantation invariably exhibit alterations of the ECM primarily due to changes in collagen. Modulation of the balance between matrix synthesis and degradation is important in the process of ventricular remodeling and in the pathophysiology of chronic heart failure. Support for the importance of the ECM and activity of matrix metalloproteinases (MMP) in the development of chronic heart failure has been demonstrated both in animal models of heart disease and in humans. A causative role for the ECM in this process was recently revealed in experiments using a transgenic mouse model that expresses the specific collagen-degrading enzyme, MMP-1, in the heart. These studies demonstrated that chronic expression of MMP-1 leads to dynamic changes in the heart and ultimately results in systolic dysfunction. Multiple studies in animal models have also shown that inhibition of MMP activity in animal models of heart failure have attenuated the onset of left ventricular dilatation. Future studies will determine whether inhibition of MMP activity improves morbidity and mortality in patients with heart failure.
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PMID:Matrix metalloproteinase disruption of the extracellular matrix and cardiac dysfunction. 1200 33

1. Peroxisome proliferator activated receptor gamma (PPARgamma) has been implicated in several cellular pathways assumed to beneficially affect heart failure progression. In contrast, population-based studies demonstrate an increased incidence of heart failure in patients treated with PPARgamma agonists. Therefore, we examined the effect of pioglitazone, a PPARgamma agonist, on chronic left ventricular remodeling after experimental myocardial infarction (MI) in mice. 2. Mice were treated with placebo or pioglitazone (20 mg x kg(-1) by gavage) from week 1 to week 6 after ligation of the left anterior descending artery. Serial transthoracic echocardiography was performed at weeks 1, 3, and 6. 3. Over 6 weeks, there was no difference in mortality (placebo 12%, pioglitazone 10%). Echocardiography showed significant left ventricular dilatation in animals with MI (week 6, end-systolic area, placebo sham 9.6+/-1.3 vs placebo MI 14.4+/-2.5 mm(2)). However, there was no difference between the placebo and pioglitazone groups (week 6, end-systolic area, pioglitazone MI 14.8+/-2.9 mm(2), P=NS vs placebo). 4. Moreover, there were no changes in metabolic parameters, inflammation, and collagen deposition. Endothelial function in the aorta was not changed by PPARgamma activation. 5. In conclusion, PPARgamma activation did not adversely affect left ventricular remodeling and survival in mice with chronic MI. However, we were also not able to identify a protective effect of pioglitazone.
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PMID:Peroxisome proliferator activated-receptor agonism and left ventricular remodeling in mice with chronic myocardial infarction. 1466 33


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