Effect of metoprolol on vulnerable plaque in rabbits by changing shear stress around plaque and reducing inflammation.

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.

A new renal artery atherosclerosis mini pig model suitable for interventional studies / 中华肾脏病杂志

Objective To establish a mini pig model suitable for interventional studies in vivo. Methods The endothelia of unilateral renal arteries in 8 purebred Chinese experimental mini pigs(CEMP)was denuded by inflated balloons after the animals were fed with high cholesterol diet for 13 weeks.The CEMP were fed with h high cholesterol diet continuously till the 40th week.The levels of blood lipid panel and creatinine were tested at week 1,14 and 40.Bilateral renal arteries were examined with intravascular uhrasonography at week 14 and 40.The vessel samples were collected at week 40 and stained with haematoxylin-eosin,Masson trichrome technique, oil O and anti-macrophage immunohistological technique. Results Significant differences of blood lipid panel and creatinine were found between week 1 and week 40.Focal ischemic renal injury could be observed pathologically.Renal arteries of CEMP were suitable for interventional procedure such as angiography and intravascular ultrasonography.Cross-sectional information of vessels could be provided clearly by intravascular ultrasonography and the intimamedian thickness of injured renal arteries was much thicker than that of non-injured ones[(0.89±0.03)mm vs (0.30±0.02)mm,P＜0.05]as evidenced by this diagnostic technique.Pathological findings demonstrated the atheroselerotic profiles of the injured renal arteries.Fibrous and fibro-fatty plaques were the main pathologic types in this CEMP model. Conclusions An animal model with renal arterial atherosclerosis mimicking the progression of atheroselerotic renovaseular disease,which is suitable for interventional procedure is established successfully.Intravascular ultasonography may have potential clinical prospect on the evaluation of atherosclerotic renovaseular disease.