Induction of angiotensin converting enzyme and angiotensin II receptors in the atherosclerotic aorta of high-cholesterol fed Cynomolgus monkeys

Significance of Chymase-Dependent Angiotensin II–Forming Pathway in the Development of Vascular Proliferation

“…Considering these findings, up to 7 days after the operation, the Ang II formation in the grafted veins is thought to be dependent mainly on the chymase-dependent Ang II-forming pathway. In fact, the Ang II concentration and the mRNA levels of fibronectin, collagen I, and collagen III, all of which are induced by an increase of Ang II action, 7,24 were significantly increased in the grafted veins 7 days after the operation, whereas they were significantly suppressed by the chymase inhibitor. Moreover, the ratio of intima to media of the grafted veins was also decreased by the chymase inhibitor 7 days after the operation.…”

Anti-atherosclerotic efficacy of olmesartan

“…1 It was previously reported that angiotensin-converting enzyme (ACE) activity in atherosclerotic lesions in monkeys fed a high-cholesterol diet was increased significantly compared with that of a normal-diet group. [3][4][5] In this atherosclerotic model, both ACE inhibitor and A II type 1 (AT 1 )-receptor antagonist significantly reduced the progression of atherosclerosis. 5 These compounds did not affect BP and plasma cholesterol level in these normotonic, hypercholesterolaemic animals.…”

“…3,5,12 Recent papers have suggested that cytokines, growth factors and adhesion molecules may relate to the development of the atherosclerosis. 3,13 Levels of pro-inflammatory cytokine, M-CSF, are reported to be upregulated with the development of atherosclerosis.…”

“…16,17 Previously, we reported that the level of TGF-␤1 mRNA in aorta was increased in monkeys fed a high-cholesterol diet but that an ACE inhibitor, imidapril, reduced lipid deposition in vascular tissues with a reduction in the increased TGF-␤1 mRNA level. 3 The intracellular adhesion molecule, ICAM-1, is also induced by A II and plays an important part in mediating the localization of monocytes in the intimal surface. 13,18 In this study, olmesartan also tended to reduce the levels of both TGF-␤1 and ICAM-1 induced by the high-cholesterol diet, though the reduction was not significant.…”

“…[1][2][3][4][5] Angiotensin II (A II) has been shown to be a potent vasoconstrictor, and it also promotes the growth of vascular smooth muscle cells via the activation of several growth factors. 1 It was previously reported that angiotensin-converting enzyme (ACE) activity in atherosclerotic lesions in monkeys fed a high-cholesterol diet was increased significantly compared with that of a normal-diet group.…”