Pathological role of receptor for advanced glycation end products in calcified aortic valve stenosis

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16601
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular surgery
• Research Institution: Kurume University
• Principal Investigator: Saku Kosuke 久留米大学, 医学部, 助教 (50771862)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 大動脈弁狭窄症 / AGEs / RAGE / 慢性炎症 / 動脈硬化

Outline of Final Research Achievements

Aortic stenosis (AS) is highly prevalent in patients with atherosclerotic cardiovascular disease. Advanced glycation end products (AGEs) and the receptor for AGEs (RAGE) play a pivotal role for vascular calcification in　atherosclerosis. We hypothesize that AGEs-RAGE axis could also be involved in the pathophysiological mechanism of AS.
54 patients with AS who underwent aortic valve replacement (AVR) were enrolled from 2014 to 2016. 16 deceased specimens and 70 serum samples without heart disease was used as controls. Valvular RAGE expression in AS was higher than controls. RAGE and αSMA were co-expressed, which were partially co-stained with osteocalcin and ALP. Serum levels of RAGE were higher in AS than controls. RAGE was independently correlated with changes in left ventricular function after AVR .In conclusions, our results suggests that RAGE may play a role in the pathogenesis of calcified AS, being a prognostic marker of patients with AS after AVR.

Free Research Field

心臓血管外科

Academic Significance and Societal Importance of the Research Achievements

本研究によって、大動脈弁狭窄症（AS）は動脈硬化と類似した病態を有し、終末糖化産物（AGEs）とその受容体RAGE（Receptor for AGEs）が、ASの病態の進行に関与することが示唆された。また、血清RAGEは、大動脈弁置換術後の心機能と相関していることも示された。以上から、RAGEはASに対する内科的治療のターゲット及び治療効果判定になる得る可能性があるだけでなく、ASに対する大動脈弁置換術後の予後を表すバイオマーカーにもなり得る可能性が考えられた。