Effect of metoprolol on vulnerable plaque in rabbits by changing shear stress around plaque and reducing inflammation
ABSTRACT The beta-adrenoceptor antagonists are known to reduce cardiovascular events, but less is known about their effects on vulnerable plaque. The purpose of this study is to explore the role of metoprolol on vulnerable plaque and the possible mechanism. Vulnerable plaque model was established by local transfection with p53 gene in New Zealand Rabbits. Metoprolol treatment attenuated vessel positive remodeling and reduced vulnerability index (1.61+/-0.58 vs. 2.33+/-0.12, P<0.01). Although the difference did not reach statistical significance, the rate of rupture of atherosclerotic plaque (31% vs. 75%) and intima-media thickness (0.05+/-0.01 vs. 0.08+/-0.01 cm) were less in the metoprolol group than in the control group. The level of shear stress-related inflammatory cytokines such as intercellular adhesion molecule 1 (ICAM-1), vascular adhesion molecule 1 (VCAM-1), matrix metalloproteinase 1 (MMP-1), were lower in the metoprolol group than in the control group (P<0.01). Compared with control group, total cholesterol and low-density lipoprotein cholesterol were lower (P<0.01) in the metoprolol group. After metoprolol treatment, shear stress increased, and was not different to baseline (physiological shear stress, P>0.05). Shear stress and vulnerability index showed a negative correlation. These findings suggest that metoprolol could inhibit the development of atherosclerosis and stabilize vulnerable plaque by regulation of lipid and reduction of inflammation, in which the change from low shear stress to physiological shear stress around plaque may play an important role.
Conference Paper: Multiscale Wireless Communications Using Compactly-Parametrized WaveletsSignals, Systems and Computers, 2005. Conference Record of the Thirty-Ninth Asilomar Conference on; 01/2005
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ABSTRACT: We assessed the effect of epinephrine on human monocytes. Monocytes were isolated from 16 healthy obese and 10 lean healthy subjects. Insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp. Obese subjects were subdivided into 2 sub-groups, insulin sensitive (IS) and insulin resistant (IR). Monocyte properties [attachment to laminin 1, migration through laminin 1, oxidized-low density lipoprotein (oxLDL) phagocytosis] were assessed pre- and post-stimulation in vitro with epinephrine. Experiments were repeated after incubation with a Na(+)/H( +) exchanger-1 inhibitor (NHE-1) (cariporide). Epinephrine increased monocyte attachment to laminin in lean and obese IR subjects through involvement of NHE-1, PKC, NO synthase, NADPH oxidase and actin polymerization. In contrast, epinephrine did not affect monocyte migration. Epinephrine increased oxLDL phagocytosis in all groups studied. Incubation with cariporide attenuated oxLDL phagocytosis. Epinephrine induces monocyte dysfunction which may be atherogenic.Angiology 01/2011; 62(1):38-45. DOI:10.1177/0003319710371616 · 2.37 Impact Factor
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ABSTRACT: To examine whether the decrease in IMT progression rate in the carotid bulb induced by metoprolol CR/XL treatment (25mg once daily) observed in the β-blocker Cholesterol-lowering Asymptomatic Plaque Study (BCAPS) was accompanied by an effect on carotid plaque echogenicity. Gray scale median (GSM) in carotid plaques, used as a score of echogenicity, was measured at baseline and after 36 months in those 341 subjects (aged 49-69 years) with an asymptomatic moderate- to large-sized carotid plaque present at baseline and at follow-up. Participants were in a factorial design assigned to treatment with metoprolol CR/XL (25mg once daily), fluvastatin (40 mg once daily) or corresponding placebo. After 36 months plaques were more echogenic in participants treated compared to those not treated with metoprolol CR/XL (57.3 ± 16.8 versus 51.8 ± 20.0, p=0.006). GSM had increased more from baseline in the metoprolol CR/XL treated subjects (25 ± 15 versus 18 ± 20, p<0.001), and plaques that had become more echolucent were less frequent in the metoprolol CR/XL treated subjects (3.6% versus 17.0%, p<0.001). Long-term treatment with low dose metoprolol CR/XL in clinically healthy subjects with moderate-sized carotid plaques was associated with increase in plaque echogenicity, suggesting a potential beneficial effect of the β-blocker treatment on plaque stability.Atherosclerosis 06/2011; 215(2):440-5. DOI:10.1016/j.atherosclerosis.2010.12.031 · 3.97 Impact Factor