Angiotensin Receptor-1 Blocker Inhibits Atherosclerotic Changes and Endothelial Disruption of the Aortic Valve in Hypercholesterolemic Rabbits

Abstract

Atherosclerotic changes in the aortic valves of rabbits fed with cholesterol were inhibited by ARB, whereas endo-thelial integrity was preserved and transdifferentiation into myofibroblasts and/or osteoblasts in valve leaflets was inhibited.

Prognostic factors for progression of early- and late-stage calcific aortic valve disease in Japanese: The Japanese Aortic Stenosis Study (JASS) Retrospective Analysis

“…21,22 An experimental study showed that in hypercholesterolemic rabbits, ARBs prevented lesion formation in the aortic valve, specifically preventing the accumulation of macrophages, myofibroblasts and osteoblasts, upregulation of osteopontin and ACE, and disruption of endothelial integrity. 23 Findings from these earlier studies and this study suggest that ARBs prevent progression of CAVD during the early stage. However, use of ACE inhibitors did not affect CAVD progression in this study.…”

Pathogenesis of Calcific Aortic Valve Disease

“…16,17,27 Interestingly, treatment with an angiotensin receptor antagonist, olmesartan, inhibited aortic valve leaflet Runx2/Cbfa1 upregulation and macrophage accumulation in the latter study. 27 As noted previously, phosphate induces vesicle formation in myofibroblasts. 67 In vascular smooth muscle cells, this effect of phosphate is mediated by its binding to the sodium-dependent phosphate cotransporter Pit1, which upregulates Runx2/Cbfa1.…”

“…76 The Runx/Cbfa1 transcription factor is increased in aortic valves of 2 hypercholesterolemic rabbit models. 16,17,27 Interestingly, treatment with an angiotensin receptor antagonist, olmesartan, inhibited aortic valve leaflet Runx2/Cbfa1 upregulation and macrophage accumulation in the latter study. 27 As noted previously, phosphate induces vesicle formation in myofibroblasts.…”

“…[22][23][24][25] The second issue is that, for many years, there were no animal models that faithfully replicated the key histological features of the disease. Recently, rabbit models been developed, 16,26,27 with that of Rajamannan and colleagues already providing a number of novel insights. 16 -18,28,29 In particular, these models have implicated the Wnt 18 and Runx2/ Cbfa1 16,17,27 signaling pathways in disease pathogenesis.…”

Telmisartan, a unique ARB, improves left ventricular remodeling of infarcted heart by activating PPAR gamma

“…6,7,37,38 On the other hand, ARBs usually inhibit TGF-b1-CTGF signaling and OPN activity, but do not affect MMP-2 or MMP-9 activity. [39][40][41][42] Thus, Telmisartan is a unique ARB that possesses potent anti-fibrotic activity via inhibition of MMP activation, OPN expression and TGF-b1-CTGF signaling.…”