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To delineate the molecular mechanism underlying the inverse agonist activity of olmesartan, a potent angiotensin II type 1 (AT1) receptor antagonist, we performed binding affinity studies and an inositol phosphate production assay. Binding affinity of olmesartan and its related compounds to wild-type and mutant AT1 receptors demonstrated that interactions(More)
OBJECTIVE Plasma high density lipoprotein (HDL) levels have been shown to be inversely correlated with coronary artery disease, but the mechanisms of the direct protective effect of HDL on endothelial cells (ECs) are not fully understood. In this study, we investigated the role of the HDL-mediated promotion of angiogenesis in human coronary artery ECs(More)
Although the sartan family of angiotensin II type 1 (AT(1)) receptor blockers (ARBs), which includes valsartan, olmesartan, and losartan, have a common pharmacophore structure, their effectiveness in therapy differs. Although their efficacy may be related to their binding strength, this notion has changed with a better understanding of the molecular(More)
The angiotensin II type 1 (AT(1)) receptor blocker (ARB) candesartan strongly reduces blood pressure (BP) in patients with hypertension and has been shown to have cardioprotective effects. A new ARB, azilsartan, was recently approved and has been shown to provide a more potent 24-h sustained antihypertensive effect than candesartan. However, the molecular(More)
Endothelial cells (ECs) are the critical cellular element responsible for postnatal angiogenesis. Since the calcium channel blocker (CCB) nifedipine indirectly upregulates endothelial superoxide dismutase expression by stimulating the production of vascular endothelial growth factor (VEGF) from smooth muscle cells (SMCs), we examined whether nifedipine(More)
ATP-binding cassette transporters (ABC) G1 and ABCA1 are membrane cholesterol transporters and have been implicated to mediate cholesterol efflux from cells in the presence of high density lipoproteins and its major protein constituent apolipoprotein A-I, respectively. We previously demonstrated that unsaturated fatty acids suppress the stimulatory effects(More)
In rat models of transplant vasculopathy, the strongest staining of CXCR3 is observed in the innermost layer of the neointima and because neointimal hyperplasia is seen after coronary angioplasty, the CXC chemokines may be targets for preventing stenosis. The expression of leukocyte surface chemokine receptors (CCR2/CCR5/CXCR2/CXCR3), as determined by flow(More)
OBJECTIVES This study analyzed the antiarrhythmogenic effect of reconstituted high-density lipoprotein (rHDL) against ischemia/reperfusion in vivo. BACKGROUND Recent studies have suggested that a reduction in the plasma HDL level may contribute to cardiac sudden death. Although there are currently only a few therapeutic strategies for increasing HDL, an(More)
Since little is known about the effects of reconstituted high-density lipoprotein (rHDL) in left ventricular (LV) remodeling, these effects were examined in rats after acute myocardial infraction (MI). Sixteen male Wistar rats were randomly divided into three groups: Sham-operated (n=6), and MI rats that received a permanent ligation around the proximal(More)
OBJECTIVE We evaluated whether a novel inducible cholesterol efflux (iCE) peptide [Fukuoka University Apolipoprotein A-I Mimetic Peptide (FAMP)] protects against myocardial ischemia reperfusion injury (IRI) through a nitric oxide (NO) pathway by an improvement of high-density lipoprotein (HDL) functionality. METHODS AND RESULTS Male C57BL6/J mice were(More)