Pathological Role of Receptor for Advanced Glycation End Products in Calcified Aortic Valve Stenosis

Autor: Kosuke Saku, Nobuhiro Tahara, Tohru Takaseya, Hiroyuki Otsuka, Kazuyoshi Takagi, Takahiro Shojima, Yusuke Shintani, Yasuyuki Zaima, Satoshi Kikusaki, Tomofumi Fukuda, Atsunobu Oryoji, Yuri Nishino, Takanori Matsui, Tatsuyuki Kakuma, Jun Akiba, Yoshihiro Fukumoto, Sho‐ichi Yamagishi, Hiroyuki Tanaka
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, Vol 9, Iss 13 (2020)
Druh dokumentu: article
ISSN: 2047-9980
DOI: 10.1161/JAHA.119.015261
Popis: Background 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 the AGEs–RAGE axis could also be involved in the pathophysiological mechanism of calcified AS. Methods and Results A total of 54 patients with calcified AS who underwent aortic valve replacement were prospectively enrolled from 2014 to 2016 (mean age 75.3±7.7 years). Aortic valve specimens were obtained from 47 patients and 16 deceased control subjects without aortic valve disease (mean age 63.2±14.5 years). The valvular expression of RAGE was evaluated by immunohistochemistry. Serum levels of AGEs and soluble RAGE were measured in 50 patients with calcified AS and 70 age‐matched and sex‐matched control subjects without heart disease. The valvular RAGE expression in patients with calcified AS was higher than controls (P=0.004) and was significantly associated with a decreased ankle‐brachial pressure index (P=0.007) and an increased intima‐media thickness (P=0.026). RAGE and α–smooth muscle actin were coexpressed and were partially costained with osteocalcin and alkaline phosphatase. The serum levels of AGEs and soluble RAGE were significantly higher in the patients with calcified AS than in the controls (P=0.013 and P
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