論文種別	原著(症例報告除く)
言語種別	英語
査読の有無	その他(不明)
表題	Vascular Endothelial NAMPT-Mediated NAD+ Biosynthesis Regulates Angiogenesis and Cardiometabolic Functions in Male Mice.
掲載誌名	正式名：Aging cell 略　 称：Aging Cell ISSNコード：14749726/14749718
掲載区分	国外
巻・号・頁	24(11),pp.e70222
著者・共著者	Shotaro Kosugi, Shintaro Yamaguchi, Ken Nishioka, Taichi Nagahisa, Yasuhiro Watanabe, Daiki Kojima, Kenji Kaneko, Ryunosuke Mitsuno, Ran Nakamichi, Yoshinaga Kawano, Kenichiro Kinouchi, Koichiro Homma, Takeshi Kanda, Junichiro Irie, Kazutoshi Miyashita, Toshiaki Monkawa, Jun Yoshino, Hiroshi Itoh, Kaori Hayashi
発行年月	2025/11
概要	Aging is associated with metabolic dysfunction and cardiovascular abnormalities. Defective nicotinamide adenine dinucleotide (NAD+) biosynthesis correlates with aging and aging-associated complications. However, the precise molecular mechanisms linking aging-associated NAD+ deficiency to cardiometabolic dysfunction remain unclear. Herein, we examined whether nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme in NAD+ biosynthesis, influences vascular endothelial function and whole-body metabolic and hemodynamic homeostasis during aging. Vascular endothelial cell-specific Nampt knockout (VeNKO) mice fed a regular chow diet exhibited no cardiometabolic abnormalities, whereas male VeNKO mice fed a high-fat diet exhibited reduced angiogenesis, resulting in impaired subcutaneous adipogenesis, impaired glucose metabolism, and hemodynamic disturbances. Mechanistically, NAMPT loss attenuated NAD+-dependent deacetylase sirtuin-1 (SIRT1) and endothelial nitric oxide synthase (eNOS) signaling, impairing angiogenesis. Aged mice exhibited endothelial NAD+ depletion driven by an imbalance between NAMPT-mediated NAD+ biosynthesis and consumption, leading to impaired eNOS signaling and associated angiogenic and cardiometabolic dysfunction, similar to that observed in VeNKO mice. Nicotinamide mononucleotide administration replenished vascular endothelial NAD+ levels, improved angiogenesis, restored subcutaneous adipose tissue volume, and ameliorated aging-associated cardiometabolic dysfunction. Collectively, our findings provide mechanistic and therapeutic insights into vascular endothelial NAMPT-NAD+-SIRT1-eNOS signaling related to aging-associated cardiometabolic disorders.
DOI	10.1111/acel.70222
PMID	41021357