オクヤマ　ミチヒロ   Michihiro Okuyama   奥山　倫弘    所属   川崎医科大学  医学部 臨床医学　心臓血管外科学    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Adipocyte Calpain-2 Deficiency Reduces Obesity-Accelerated Abdominal Aortic Aneurysm Formation in Mice.
掲載誌名	正式名：FASEB bioAdvances 略　 称：FASEB Bioadv ISSNコード：25739832/25739832
掲載区分	国外
巻・号・頁	7(10),pp.e70061
国際共著	国際共著
著者・共著者	Ana Clara Frony, Aida Javidan, Weihua Jiang, Michihiro Okuyama, Lihua Yang, Haruhito A Uchida, Venkateswaran Subramanian
発行年月	2025/10
概要	Abdominal adiposity is associated with increased risk of abdominal aortic aneurysm (AAA) development. Calpains are non-lysosomal calcium-dependent cysteine proteases that are highly expressed in human and experimental AAAs. Using a pharmacological inhibitor and genetically deficient mice, we previously demonstrated that calpain-2 (a major ubiquitous isoform) deficiency mitigated angiotensin II (AngII)-induced AAA formation in hypercholesterolemic mice. In addition, we also demonstrated that calpain inhibition strongly suppressed adipose tissue inflammation in obese mice. Here, we evaluated the contribution of adipocyte-specific calpain-2 on obesity-accelerated AAA in mice. Calpain-2 protein is highly expressed in the periaortic adipose tissue (PAAT) of AngII-induced AAAs in obese mice. To determine the relative contribution of calpain-2 in obesity-accelerated AAA development, calpain-2 floxed mice were bred to mice with a tamoxifen-inducible form of Cre under control of either the ubiquitous promoter, chicken β-actin, or adipocyte-specific promoter, Adipoq. Ubiquitous or adipocyte-specific depletion of calpain-2 in mice significantly suppressed Ang II-induced AAA formation in obese mice. In addition, calpain-2 depletion reduced the incidence of AngII-induced AAAs in mice. Furthermore, calpain-2 deficiency prevented AngII-induced aortic medial elastin fragmentation, adventitial collagen disruption, and periaortic leukocytic accumulation. These results suggest that adipocyte-derived calpain-2 plays a critical role in AngII-induced AAA development in diet-induced obese mice.
DOI	10.1096/fba.2025-00202
PMID	41112958