AIMS: Angiogenesis is critical for re-establishing blood supply to ischaemic myocardium after myocardial infarction (MI). Human studies have associated arterial baroreflex (ABR) deficiency with higher rate of sudden death after MI. The present work was designed to examine whether ABR deficiency affects angiogenesis in MI rats. METHODS AND RESULTS: Baroreflex sensitivity (BRS) was determined in conscious rats at 1 month after occlusion of the left anterior descending coronary artery. The survival time was significantly shorter in Sprague-Dawley rats with BRS <0.60 ms/mmHg vs. those with BRS ≥0.60 ms/mmHg. Sinoaortic denervation destroyed ABR, and decreased capillary density, regional blood flow and vascular endothelial growth factor (VEGF) concentration after MI. Ketanserin (0.6 mg/kg/day) enhanced BRS, and increased capillary density, regional blood flow, and VEGF. Sinoaortic denervation also reduced the expression of vesicular acetylcholine (ACh) transporter and α7-nicotinic ACh receptor (α7-nAChR). Angiogenesis after MI was significantly attenuated in α7-nAChR knockout mice. In contrast, increase in endogenous ACh with cholinesterase inhibitor pyridostigmine (30 mg/kg/day) increased angiogenesis after MI. In cultured cardiac microvascular endothelial cells, ACh stimulated the expression of VEGF, phosphorylation of VEGF receptor 2, and tube formation in a manner dependent upon α7-nAChR. CONCLUSION: Our results demonstrated that ABR deficiency could attenuate angiogenesis in ischaemic myocardium. These findings provide further mechanistic basis for enhancing baroreflex function in the treatment of MI.
AIMS: Angiogenesis is critical for re-establishing blood supply to ischaemic myocardium after myocardial infarction (MI). Human studies have associated arterial baroreflex (ABR) deficiency with higher rate of sudden death after MI. The present work was designed to examine whether ABR deficiency affects angiogenesis in MI rats. METHODS AND RESULTS: Baroreflex sensitivity (BRS) was determined in conscious rats at 1 month after occlusion of the left anterior descending coronary artery. The survival time was significantly shorter in Sprague-Dawley rats with BRS <0.60 ms/mmHg vs. those with BRS ≥0.60 ms/mmHg. Sinoaortic denervation destroyed ABR, and decreased capillary density, regional blood flow and vascular endothelial growth factor (VEGF) concentration after MI. Ketanserin (0.6 mg/kg/day) enhanced BRS, and increased capillary density, regional blood flow, and VEGF. Sinoaortic denervation also reduced the expression of vesicular acetylcholine (ACh) transporter and α7-nicotinic ACh receptor (α7-nAChR). Angiogenesis after MI was significantly attenuated in α7-nAChR knockout mice. In contrast, increase in endogenous ACh with cholinesterase inhibitor pyridostigmine (30 mg/kg/day) increased angiogenesis after MI. In cultured cardiac microvascular endothelial cells, ACh stimulated the expression of VEGF, phosphorylation of VEGF receptor 2, and tube formation in a manner dependent upon α7-nAChR. CONCLUSION: Our results demonstrated that ABR deficiency could attenuate angiogenesis in ischaemic myocardium. These findings provide further mechanistic basis for enhancing baroreflex function in the treatment of MI.
Authors: Gaetano M De Ferrari; Antonio Sanzo; Grazia Maria Castelli; Annalisa Turco; Alice Ravera; Fabio Badilini; Peter J Schwartz Journal: J Cardiovasc Transl Res Date: 2014-07-29 Impact factor: 4.132
Authors: Cristiano Mostarda; Bruno Rodrigues; Alessandra Medeiros; Edson D Moreira; Ivana C Moraes-Silva; Patricia C Brum; Katia De Angelis; Maria-Cláudia Irigoyen Journal: Am J Transl Res Date: 2014-05-15 Impact factor: 4.060
Authors: Stephen Baine; Ingrid Bonilla; Andriy Belevych; Andrei Stepanov; Lisa E Dorn; Radmila Terentyeva; Dmitry Terentyev; Federica Accornero; Cynthia A Carnes; Sandor Gyorke Journal: J Cell Mol Med Date: 2021-03-23 Impact factor: 5.310