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 chronic elevation in ventricular wall stress secondary to ventricular volume or pressure overload leads to structural remodeling of the muscular, vascular and extracellular matrix components of the myocardium. While initially a compensatory response, the progressive hypertrophy and ventricular dilatation induced by this condition ultimately have a detrimental effect on ventricular function, resulting in heart failure. Fibrillar collagen provides the skeletal framework which interconnects the cardiomyocytes, thereby maintaining ventricular shape and size and contributing to tissue stiffness. Accordingly, these myocardial collagen fibers must be disrupted for ventricular dilatation, sphericalization and wall thinning to occur. The presence of an abundant, latent matrix metalloproteinase (MMP) population which coexists with myocardial fibrillar collagen has been documented. Thus, the potential for collagen degradation to exceed synthesis exists should there be significant activation of this latent MMP system. Mast cells are known to store and release a variety of biologically active mediators including TNF-alpha and proteases such as tryptase and chymase, which can induce MMP activation. Increased cardiac mast cell density has been implicated in the pathophysiology of human end-stage cardiomyopathy and experimental myocardial infarction, hypertension and chronic volume overload secondary to mitral regurgitation and aorto-caval fistula. The potential role of cardiac mast cells in activating MMPs, which then results in fibrillar collagen degradation and adverse myocardial remodeling secondary to chronic volume and pressure overload will be the subject of this review.
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PMID:Cardiac mast cell regulation of matrix metalloproteinase-related ventricular remodeling in chronic pressure or volume overload. 1637 24

Human chymase activates not only angiotensin II but also transforming growth factor-beta, a major stimulator of myocardial fibrosis, while rat chymase activates transforming growth factor-beta, but not angiotensin II. To clarify the role of chymase-dependent transforming growth factor-beta activation, we evaluated whether chymase inhibition prevents cardiac fibrosis and cardiac dysfunction after myocardial infarction in rats. Myocardial infarction was induced by ligation of the left anterior descending coronary artery. One day after the ligation, rats were randomized into 2 groups: 1) a chymase-treated group that received 10 mg/kg per day of the chymase inhibitor NK3201 orally for 4 weeks; and 2) a vehicle group of non-treated rats with myocardial infarction. We also included a control group who underwent sham-operation and no treatment. Four weeks after ligation, echocardiography revealed that chymase inhibitor treatment reduced the akinetic area and increased fractional area change but did not significantly change left ventricular end-diastolic area. Chymase inhibition significantly reduced left ventricular end-diastolic pressure, increased the maximal end-systolic pressure-volume relationship and decreased the time constant of left ventricular relaxation. Chymase activity in the non-infarcted myocardium was significantly increased in the vehicle group, but it was significantly reduced by chymase inhibitor treatment. The fibrotic area in the cardiac tissues and the mRNA levels of collagen I and collagen III were also significantly lower in the chymase inhibitor-treated group than in the vehicle group. Therefore, the pathway forming chymase-dependent transforming growth factor-beta may play an important role in myocardial fibrosis and cardiac dysfunction rather than left ventricular dilatation after myocardial infarction.
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PMID:Chymase inhibition prevents cardiac fibrosis and dysfunction after myocardial infarction in rats. 1671 54