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Soluble RAGE attenuates Ang II-induced arterial calcification via inhibiting AT1R-HMGB1-RAGE axis

Jisu Jeong1, Soyoung Cho1, Miran Seo2

  • 1Graduate Program in Science for Aging, Yonsei University, Seoul, South Korea; Integrative Research Center for Cerebrovascular and Cardiovascular Diseases, Division of Cardiology, Yonsei University College of Medicine, Seoul, South Korea.

Atherosclerosis
|March 12, 2022
PubMed
Abstract

Insights

Soluble RAGE (sRAGE) effectively blocks angiotensin II (Ang II)-induced arterial calcification by inhibiting the HMGB1/RAGE pathway. This finding highlights sRAGE as a potential therapeutic for atherosclerosis.

Area of Science:

  • Cardiovascular Research
  • Molecular Biology
  • Pathogenesis of Atherosclerosis

Background:

  • Arterial calcification (AC) is a key factor in atherosclerosis development.
  • Angiotensin II (Ang II), a renin-angiotensin system (RAS) effector, accelerates AC.
  • Receptor for advanced glycation end-product (RAGE) signaling is implicated in AC, but its precise role with Ang II is unclear.

Purpose of the Study:

  • To investigate RAGE-mediated signaling in Ang II-induced AC.
  • To evaluate the therapeutic potential of soluble RAGE (sRAGE) in this process.

Main Methods:

  • Utilized human aortic smooth muscle cells (HAoSMCs) and apolipoprotein E knockout (ApoE KO) mice.
  • Examined Ang II-induced calcification, HMGB1 release, and RAGE pathway activation.
  • Assessed the effects of HMGB1 neutralizing antibody and sRAGE.

Main Results:

  • Ang II significantly increased HAoSMC calcification via HMGB1 release and RAGE activation.
  • Both HMGB1 antibody and sRAGE inhibited Ang II-induced calcium deposition.
  • sRAGE treatment reduced HMGB1 secretion and RAGE signaling activation.
  • In vivo studies confirmed sRAGE attenuated Ang II-induced aortic calcification.

Conclusions:

  • Blockade of RAGE with sRAGE effectively reduces Ang II-induced arterial calcification.
  • The HMGB1/RAGE pathway is a critical mediator of Ang II-induced AC.
  • sRAGE shows promise as a therapeutic agent for arterial calcification.
Keywords:
Angiotensin II type 1 receptor (AT1R)Arterial calcificationRAGESoluble RAGE

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