Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vascular tissues, chymase catalyzes the production of angiotensin II, which plays a crucial role in vascular diseases. Recent clinical studies and animal models of vascular proliferation and atherosclerosis have provided evidence that angiotensin II formed by chymase is involved in these processes. These observations suggest that chymase might promote the development of vascular proliferation and atherosclerosis. Chymase also activates matrix metalloproteinase 9, which promotes aortic aneurysm and angiogenesis, and thus chymase inhibitors might also prevent the progression of abdominal aortic aneurysm and angiogenesis. We propose that chymase is a novel target for preventing vascular diseases.
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PMID:Chymase as a novel target for the prevention of vascular diseases. 1538 Sep 35

Abdominal aortic aneurysm is a multifactorial disease with genetic risk factors and an immunologic component. Immune cells, including macrophages, neutrophils, mast cells, B- and T- lymphocytes, along with vascular smooth muscle cells and adventitial fibroblasts, produce cytokines and enzymes, promoting an inflammatory reaction, extracellular matrix degradation, and neovascularization. Among the different enzymes secreted by immune and stromal cells, matrix metalloproteinase (MMP)-2, MMP-9, MMP-12, cathepsins, and neutrophil elastase cause medial degeneration. Chymase causes smooth muscle cell apoptosis, and MMP-3, MMP-8, and MMP-13 cause adventitial collagen degradation, promoting abdominal aortic aneurysm rupture. At the same time chemokines (interleukin 8, macrophage inflammatory protein 1 alpha, monocyte chemotactic protein-1) cause recruitment and proliferation of inflammatory cells, whereas cytokines (vascular endothelial growth factor and transforming growth factor-beta) promote neoangiogenesis.
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PMID:Immune cells and molecular mediators in the pathogenesis of the abdominal aortic aneurysm. 1969 Apr 70

Chymase plays a crucial role in angiotensin II formation in various tissues. Angiotensin II induces gene expression of transforming growth factor (TGF)-beta and matrix metalloproteinase (MMP)-9 precursors, and chymase can convert precursors of TGF-beta and MMP-9 to their active forms. In cultured fibroblasts, significant increases in cell growth and TGF-beta levels were observed after chymase injection; these increases were inhibited by a chymase inhibitor, but not by an angiotensin II-receptor blocker. In apolipoprotein E-deficient mice, abdominal aortic aneurysm (AAA) development depends on an increase in MMP-9 activities induced by angiotensin II infusion, but the inhibition of MMP-9 activation by a chymase inhibitor resulted in attenuation of the angiotensin II-induced AAA development. The upregulation of MMP-9 and TGF-beta levels is involved in damage to various organs, but these gene expressions are not completely induced by angiotensin II alone. Therefore, chymase inhibition may be useful for attenuating MMP-9 and TGF-beta levels, in addition to reducing angiotensin II formation, and this function may provide powerful organ protection. In this review, we propose the possible use of chymase inhibitors as agents to prevent organ damage.
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PMID:New approaches to blockade of the renin-angiotensin-aldosterone system: chymase as an important target to prevent organ damage. 2067 58