Key result
High serum cholesterol correlated with arterial chymase activity in humans and hamsters, and an orally active nonpeptide chymase inhibitor prevented lipid deposition in hamsters.
Why the study?
Does an orally active nonpeptide chymase inhibitor prevent lipid deposition in Syrian hamsters fed a high cholesterol diet?
Does an orally active nonpeptide chymase inhibitor prevent lipid deposition in Syrian hamsters fed a high cholesterol diet?
Chymase upregulation is associated with high cholesterol and may facilitate atherosclerosis, a process that can be attenuated by a chymase inhibitor in animal models.
Chymase inhibition may attenuate atherosclerosis in hypercholesterolemia; leaves open translation to human therapy.
The renin-angiotensin system has been studied and recognized as one of the major blood pressure-regulating systems for the past century. In the last quarter century, however, many alternative pathways of angiotensin II formation have been found, and among them, chymase has been a focus of interest because of its specificity and potency in the human cardiovascular system. Chymase evidently is not involved in functional regulation of blood pressure at least in the short term, but evidence is accumulating that it may be involved in structural remodeling of the cardiovascular system. We found increased vascular chymase activity in atherosclerotic lesions of the human aorta as well as in cardiac remodeling after myocardial infarction. We found a significant positive correlation between serum total or LDL cholesterol levels and arterial chymase-dependent angiotensin II-forming activity in patients who were undergoing coronary artery bypass operation, suggesting that high serum cholesterol may trigger upregulation of vascular chymase and facilitate the development of atherosclerosis. This hypothesis was tested in Syrian hamsters fed a high cholesterol diet containing 0.5% cholesterol: A marked lipid deposition in the aortic cusp developed and the plasma cholesterol levels were positively correlated with aortic chymase activity. An orally active nonpeptide chymase inhibitor almost canceled this lipid deposition. These clinical and experimental data indicated an association between cholesterol and vascular chymase upregulation that may facilitate the development of atherosclerosis.
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Arakawa et al. (2000) studied Atherosclerosis. High serum cholesterol and chymase inhibitor was evaluated on Arterial chymase-dependent angiotensin II-forming activity and lipid deposition. High serum cholesterol correlated with arterial chymase activity in humans and hamsters, and an orally active nonpeptide chymase inhibitor prevented lipid deposition in hamsters.
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