Background and aims: Arterial calcification (AC), which is an important process in the pathogenesis of atherosclerosis, is accelerated by angiotensin II (Ang II), a critical effector of the renin-angiotensin system (RAS). Receptor for advanced glycation end-product (RAGE) is an important pattern recognition receptor downstream of Ang II. Although recent studies have suggested an association between RAGE-mediated signaling and RAS in AC, the detailed mechanism, particularly in relation to Ang II, remains unclear. Methods: Therefore, we investigated the role of RAGE-mediated signaling pathways and the therapeutic efficacy of soluble RAGE (sRAGE) in Ang II-induced AC, using both a human aortic smooth muscle cell (HAoSMC) model, and an in vivo apolipoprotein E knockout (ApoE KO) mouse model. Results: According to our data, Ang II significantly increased the calcification of HAoSMCs, and the associated activation of RAGE was mediated by subsequent HMGB1 release through Angiotensin II type 1 receptor activation. Both HMGB1 neutralizing antibody and sRAGE inhibited Ang II-induced calcium deposition. Furthermore, sRAGE attenuated HMGB1 secretion and the activation of RAGE-mediated signaling. The in vivo study indicated that Ang II significantly induced calcium deposition in the aorta, and this was significantly attenuated by sRAGE. Conclusions: Our findings strongly suggest that blockade of RAGE, using sRAGE, effectively attenuates Ang II-induced arterial calcification.
|Number of pages||10|
|Publication status||Published - 2022 Apr|
Bibliographical noteFunding Information:
This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) grant funded NRF-2018R1A1A1A05078230 (S. Lim), NRF-2020R1A2C1007103 (S. Park), NRF-2019R1A2C1088428 (M. Seo), and by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) grant funded by the Ministry of Health & Welfare ( HI20C1566 , Y. Jang).
© 2022 Elsevier B.V.
All Science Journal Classification (ASJC) codes
- Cardiology and Cardiovascular Medicine