Abstract 553: Relaxin Attenuates Angiotensin II--Induced Proinflammatory Signaling in Vascular Smooth Muscle Cells
Relaxin 2 (RLX) was traditionally considered a reproductive hormone. However, recent studies indicate that it also has potent short-term vasodilatory and long-term arterial remodeling and anti-fibrotic effects. Based on these findings, a recombinant form of relaxin, Serelaxin, was successfully used in treatment of the acute heart failure. In the present study, we tested the hypothesis that RLX can attenuate the Angiotensin II (Ang II) mediated vascular inflammation. Ang II, the principal hormone of the renin-angiotensin system, can induce secretion of the Monocyte Chemoattractant Protein-1 (MCP-1) and Interleukin 6 (IL-6). Release of these proinflammatory mediators is an initial step in vascular inflammation, an important early component in the development of cardiovascular disease. Utilizing ELISA, we observed that RLX pretreatment inhibited Ang II-induced secretion of MCP-1 and IL-6 by 70 (p<0.05) and 87% (p<0.05), respectively, in human aortic smooth muscle cells. The same effect was achieved in isolated mouse aortas. We next studied the effect of RLX on Ang II-induced activation of the NFκB pathway and ROS signaling. RLX pretreatment inhibited Ang II-mediated induction of NADPH oxidase 5 expression and production of H2O2 as measured by the sensor HyPer. RLX also prevented P65 phosophorylation and nuclear translocation in response to Ang II. We conclude that RLX inhibits secretion of IL-6 and MCP-1 likely through interference with ROS-mediated NFκB activation. Via this mechanism, RLX may thus represent a therapeutic treatment of pro-inflammatory cardiovascular conditions such as acute heart failure, peripheral arterial disease, and aortic aneurysms.
Author Disclosures: S. Vukelic: None. B. Lassegue: None. K. Griendling: None.
- © 2014 by American Heart Association, Inc.