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)

Congestive heart failure is often preceded by a latent or preclinical phase in which patients are relatively asymptomatic. During this period, there is neuroendocrine activation, left ventricular dysfunction, and remodeling of the heart. The extent to which these activities are interrelated is unclear, but it appears from experimental studies that myocardial damage is associated with chronic sympathetic nervous system activation, left ventricular hypertrophy, and a subsequent increase in left ventricular volume. The nondamaged myocardial tissue demonstrates enhanced messenger RNA for angiotensinogen and angiotensin converting enzyme activity. Angiotensin II along with other trophic signals may prime the cell for "growth." Alteration of left ventricular function may produce unusual loading conditions on the myocardium. Stretch of membrane-bound ion channels may impart mechanical signals that may be transduced and expressed as cellular hypertrophy. Interstitial collagenase may be activated, leading to disruption of the collagen-supporting network. Elongated cells (eccentric hypertrophy), cell slippage, and cell dropout may contribute to the dilatative process. The end product is cardiac dilatation, inefficient left ventricular performance, and congestive heart failure. We have observed that an increase in left ventricular mass is the initial morphological response to acute myocardial damage in a canine model. This occurs at 1 week and is followed by progressive activation of the sympathetic nervous system, left ventricular dilatation, and modest left ventricular dysfunction, a condition that mimics preclinical heart failure in patients. The remodeling process in the canine model, including the increase in mass and volume, may be blocked by angiotensin converting enzyme inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neurohumoral activation in preclinical heart failure. Remodeling and the potential for intervention. 809 70

The purpose of the present study was to assess whether the insertion (I)/deletion (D) polymorphism of the angiotensin converting enzyme (ACE) gene, and the polymorphism of angiotensinogen (AGT) gene with threonine (T) instead of methionine (M) at amino acid 235 in exon 2 (M235T) were associated with left ventricular dilatation after myocardial infarction. In 103 patients with myocardial infarction, the left ventricular (LV) end-diastolic volume index (EDVI) and the end-systolic volume index (ESVI) were assessed by echocardiography at two time points, namely at 7 +/- 4 days and at 3.9 +/- 1.3 months (mean +/- S.D.) after the infarction. The increases in the LVEDVI and LVESVI on the second echocardiogram were significantly higher in subjects with the DD and ID genotypes than in patients with the II genotype (P < 0.05 and P < 0.005, respectively). Multiple regression analysis revealed that the LVESVI at the first echocardiographic examination and the ACE I/D genotype were significant predictors of the LVEDVI and LVESVI at the second echocardiographic examination. However, the AGT M235T genotype was eliminated. In conclusion, the DD and ID genotypes of the ACE gene were significantly associated with the progression of the LVEDVI and LVESVI after myocardial infarction. The presence of the deletion allele of the ACE gene may be a risk factor of congestive heart failure after a myocardial infarction.
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PMID:Genetic basis of left ventricular remodeling after myocardial infarction. 879 80

Coronary heart disease is a multifactorial disease, influenced by environmental and genetic factors. Experimental and clinical data show that the renin-angiotensin system has important indications in coronary artery disease by influencing progressive ventricular dilatation, ventricular function, and outcome. Angiotensin II may have direct toxic effects on myocardial cells, induce hypertrophy in noninfarcted areas, activate the sympathetic nervous system, stimulate fibroblast proliferation, vasoconstrict coronary vessels, increase left ventricular afterload, and impair diastolic relaxation. Associations between a polymorphism of the angiotensinogen gene and angiotensin-converting enzyme gene and the occurrence of myocardial infarction have been reported. Patients with the DD genotype (ACE gene) have higher plasma ACE and myocardial ACE activity. Preliminary data suggest that the DD genotype is associated with more progressive ventricular dilatation post myocardial infarction and with a greater response after ACE inhibition. The DD genotype is also associated with a higher incidence of left ventricular hypertrophy, which may have implications for the induction of hypertrophy in noninfarcted areas. Whatever the mechanisms, chronic ACE inhibition, started early after myocardial infarction, improves survival and reduces mortality and morbidity for major cardiovascular events.
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PMID:Role of the renin-angiotensin system as a risk factor for control of morbidity and mortality in coronary artery disease. 911 54