Influence of Nebivolol and Metoprolol on Inflammatory Mediators in Human Coronary Endothelial or Smooth Muscle Cells. Effects on Neointima Formation After Balloon Denudation in Carotid Arteries of Rats Treated with Nebivolol

Abstract

Objective and Background: Inflammation plays a critical role in all stages of atherogenesis. Proliferating vascular smooth muscle cells (SMC) and endothelial cells (EC) enhancing the inflammatory response, both contribute to the progression of atherosclerosis. Anti-proliferative, anti-inflammatory and anti-oxidative therapy seems to be a promising therapeutic strategy. The aim of this study was to assess the anti-proliferative and anti-inflammatory effect of the β-blocker nebivolol in comparison to metoprolol in vitro and to find out whether nebivolol inhibits neointima formation in vivo. Methods and Results: Real-time-RT-PCR revealed a decrease in VCAM-1, ICAM-1, PDGF-B, E-selectin and P-selectin mRNA expression in human coronary artery EC and SMC incubated with nebivolol for 72 hours while metoprolol did not have this effect. Nebivolol reduced MCP-1 and PDGF-BB protein in the culture supernatant of SMC and EC, respectively. Sprague-Dawley rats were treated with nebivolol for 0 or 35 days before and 28 days after carotid balloon injury. Immunohistological analyses showed that pre-treatment with nebivolol was associated with a decreased number of SMC layers and macrophages and an increased lumen area at the site of the arterial injury. The intima area was reduced by 43% after pre-treatment. Conclusion: We found that nebivolol reduced the expression of proinflammatory genes in endothelial cells and vascular smooth muscle cells in vitro whereas metoprolol did not. In vivo, nebivolol inhibited neointima formation by reducing SMC proliferation and macrophage accumulation.

Nebivolol, but Not Metoprolol, Improves Endothelial Function of the Corpus Cavernosum in Apolipoprotein E-Knockout Mice

“…Moreover, atherosclerotic plaque formation in the aortic root as well as reactive oxygen species (ROS) production was decreased or even normalized by nebivolol, whereas metoprolol had less or no effects. These results are consistent with recent findings indicating the beneficial role of nebivolol on endothelial function in different animal models (Oelze et al, 2006;Wolf et al, 2007). Comparable effects could be observed in the penile tissue.…”

Major differences in gene expression in human coronary smooth muscle cells after nebivolol or metoprolol treatment

“…The inhibition of MCP-1 secretion in vascular smooth muscle cells by nebivolol might therefore reduce monocyte recruitment and slow down plaque formation. This reduction in inflammatory cells in combination with reduced plaque size could be demonstrated for nebivolol treated rats after carotid artery denudation [34].…”

The Role of Inflammation in Myocardial Infarction

“…Recent research has shown that beta-blockers appear to have only a minimal (nebivolol) or no effect (metoprolol) on proinflammatory genes in endothelial cells [233]. In contrast, in another study carvedilol (a beta-blocker well known for its anti-inflammatory and antioxidant properties) [234] was found to suppress plasma levels of TNF-α and IL-6 in ischemic and nonischemic dilated cardiomyopathy, but with effects more marked in nonischemic patients [235].…”