Journal of Cardiovascular Pharmacology 2014-07-01

β-Blockers promote angiogenesis in the mouse aortic ring assay.

Tonino Stati, Marco Musumeci, Sonia Maccari, Alessia Massimi, Elisa Corritore, Georgios Strimpakos, Elvira Pelosi, Liviana Catalano, Giuseppe Marano

文献索引：J. Cardiovasc. Pharmacol. 64(1) , 21-7, (2014)

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摘要

Recent results indicate that the reduction of β-adrenergic signaling impairs angiogenesis under ischemic conditions. Because angiogenesis may occur in the absence of ischemia, it remains to be determined whether and how β-adrenergic signaling regulates angiogenesis, which develops under normoxic conditions. The effect of β-adrenergic ligands on angiogenesis was investigated using 3-dimensional cultures of mouse aortic rings embedded in collagen type I, in which luminized microvessels develop in response to vascular endothelial growth factor (VEGF). Under normoxic conditions, both isoproterenol, a β-adrenergic receptor (β-AR) agonist, and forskolin, an adenylate cyclase activator, were unable to influence aortic microvessel sprouting. On the contrary, treatment with propranolol, a β-AR antagonist, caused an approximately 70% increase in VEGF-mediated microvessel sprouting. This effect was abolished in rings from both double β-AR and β1-AR knockout mice, but not in rings from β2-AR knockout mice. Significant increases in microvessel sprouting were also observed when mouse aortic rings from C57BL/6 mice were treated with the β1-AR-selective antagonists metoprolol and bisoprolol or with the β2-AR-selective antagonist ICI 118,551. Conversely, carvedilol, a nonselective β-AR antagonist, was unable to affect aortic sprouting. These findings suggest that some β-blockers display proangiogenic activity through a mechanism that is independent of their ability to antagonize catecholamine action. The present results also identify a new function for β-AR signaling as a facilitator for VEGF-mediated angiogenesis and have implications for understanding the mechanisms that regulate angiogenic responses under normoxic conditions.