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Calcitonin gene-related peptide attenuates angiotensin II-induced ROS-dependent apoptosis in vascular smooth muscle
Hong-Min Luo1, Xia Wu2, Wen-Xuan Liu3
1Department of Nephrology, Third Hospital, Hebei Medical University, Shijiazhuang, China.
Abstract:
Apoptosis is associated with various cardiovascular diseases. CGRP exerts a variety of effects within the cardiovascular system, and protects against the onset and development of angiotensin (Ang) II-induced vascular dysfunction and remodelling. However, it is not known whether CGRP has a direct effect on Ang II-induced apoptosis in vascular smooth muscle cells (VSMCs), and the mechanism underlying the anti-apoptotic role remains unclear. In this study, CGRP significantly suppressed reactive oxygen species (ROS) and apoptosis in Ang II-induced VSMCs. In VSMCs pre-treated with a CGRP receptor antagonist (CGRP8-37), the CGRP-mediated inhibition of Ang II-induced ROS and apoptosis was completely abolished. Moreover, pre-treatment with N-acetyl-L cysteine (NAC), an ROS scavenger, blocked the effects of CGRP on Ang II-induced apoptosis. In addition, the activation of CaMKII and the downstream transcription factor CREB stimulated by Ang II was abrogated by CGRP. Importantly, in both CGRP and NAC-treated VSMCs, CGRP failed to further attenuate CaMKII and CREB activation. The results demonstrate that CGRP attenuated Ang II-induced ROS-dependent apoptosis in VSMCs by inhibiting the CaMKII/CREB signalling pathway.
Insights
Calcitonin gene-related peptide (CGRP) protects against angiotensin II-induced apoptosis in vascular smooth muscle cells by reducing reactive oxygen species (ROS) and inhibiting the CaMKII/CREB pathway.
Area of Science:
- Cardiovascular Biology
- Cellular Signaling
- Molecular Medicine
Background:
- Apoptosis is implicated in cardiovascular diseases.
- Calcitonin gene-related peptide (CGRP) has protective cardiovascular effects.
- CGRP's direct impact on angiotensin II-induced vascular smooth muscle cell (VSMC) apoptosis and its mechanism are unknown.
Purpose of the Study:
- To investigate the effect of CGRP on angiotensin II-induced apoptosis in VSMCs.
- To elucidate the underlying mechanism of CGRP's anti-apoptotic action.
Main Methods:
- VSMCs were treated with angiotensin II, CGRP, CGRP receptor antagonist (CGRP8-37), and N-acetyl-L cysteine (NAC).
- Reactive oxygen species (ROS) production and apoptosis were measured.
- Activation of CaMKII and CREB signaling pathways was assessed.
Main Results:
- CGRP significantly suppressed angiotensin II-induced ROS and apoptosis in VSMCs.
- CGRP receptor antagonism abolished CGRP's protective effects.
- ROS scavenging with NAC blocked CGRP's effect on apoptosis.
- CGRP inhibited angiotensin II-induced activation of CaMKII and CREB.
Conclusions:
- CGRP attenuates angiotensin II-induced apoptosis in VSMCs.
- This effect is mediated by the reduction of ROS.
- The mechanism involves the inhibition of the CaMKII/CREB signaling pathway.
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