Immunoregulatory gene GIMAP6 suppresses lethal atherosclerotic vasculopathy and ischemic heart failure

作者：Chen Xiang, Kaja S. Arusha, Danielle Springer, Sachiko Nakamori, Ping Jiang, Zhihong Yang, Jing Cui, Yu Zhang, Huie Jing, Ann Y. Park, Maria H Zhu, Sarah Weber, Deniz Cagdas, Hassan Abolhassan, Nasrin Behniafard, Margery Smelkinson, Qihui Liang, Elif Everest, Julia Kun, Alyssa Grogan, Jennifer Treat, Christa S. Zerbe, Steven M Holland, Renu Virmani, Alan T Remaley, Helen Su, Lixin Zheng, Michael J Lenardo · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2026 · DOI：10.64898/2026.01.26.701509 · 研究领域：Atherosclerosis and Cardiovascular Diseases、Inflammasome and immune disorders、interferon and immune responses

SUMMARY Controlling hyperlipidemia has reduced but not eliminated atherosclerotic cardiovascular disease as a predominant cause of human mortality. Here, we report that loss of the immunoregulatory gene GTPase of immunity-associated protein 6 ( GIMAP6 ), causes an inflammatory vasculopathy and accelerated atherosclerosis in the absence of hyperlipidemia. These pathologic changes in turn result in progressive cardiac ischemia, myocardial infarction, and heart failure, culminating in early death. In humans, rare deleterious GIMAP6 variants are associated with premature severe cardiovascular disease. These findings reveal GIMAP6 to play an important protective role against atherosclerotic cardiovascular disease whose identification offers opportunities for improved risk management and a target for new therapies.