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journal article·2025-10Open access

Leptin Aggravates Thoracic Aortic Dissection Through Impairment of Energy Metabolism in Nrip2 + Smooth Muscle Cells

Ling Chen, Yujie Zhu, Xi Yang, JiangBin Wu, Keyuan Chen, Wuqing Huang, Lu Fang, Qi Zhang, Jie Chen, Jianing Gao, Huanhuan Cao, Meifang Wu, Zhihuang Qiu, Yuling Zhang, Yue Shen, Qiuyu Huang, Zhiyong Lin, Lemin Zheng, Liangwan Chen

Advanced Science· Volume 12· Issue 38
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Abstract

Abstract Obesity is a significant risk factor for thoracic aortic dissection (TAD), as supported by UK Biobank data showing obese individuals have a higher risk of TAD. The study investigates leptin, a hormone elevated in obesity, and finds that hyperleptinemia is common in TAD patients, suggesting its role in disease pathogenesis. Using leptin‐knockout mice, it is demonstrated that exogenous leptin exacerbates TAD by promoting phenotypic transitions in vascular smooth muscle cells (VSMCs). These adverse effects are reversible with pharmacologic leptin blockade, indicating potential therapeutic benefits. Single‐cell RNA sequencing reveals a novel smooth muscle cells (SMC) cluster, Nrip2 + , in the aorta, with a distinct contractile gene profile. Increased Nrip2 + VSMCs are linked to enhanced mitochondrial energy metabolism. Elevated Nrip2 + VSMCs inhibit the leptin‐induced transition from a contractile to a synthetic phenotype, reducing TAD incidence. The findings suggest that high blood leptin levels contribute to the increased TAD risk in obese individuals by suppressing Nrip2 + SMCs, leading to abnormal mitochondrial metabolism and VSMC phenotypic transitions. Thus, targeting leptin to boost Nrip2 + VSMC metabolic activity is a promising strategy for TAD prevention and treatment.
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Research context

OpenAlex topics: Single-cell and spatial transcriptomics · Adipose Tissue and Metabolism · MicroRNA in disease regulation

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Cardiovascular Surgery Fujian Medical University Union Hospital Fuzhou 350100 China

Key Laboratory of Cardio‐Thoracic Surgery (Fujian Medical University) Fujian Province University Fuzhou 350001 China

The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine School of Basic Medical Sciences State Key Laboratory of Vascular Homeostasis and Remodeling NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides Beijing Key Laboratory of Cardiovascular Receptors Research Health Science Center Peking University Beijing 100191 China

Department of Epidemiology and Health Statistics School of Public Health Fujian Medical University Fuzhou Fujian 350004 China

Department of Cardiovascular Affiliated Hospital of Putian University Putian Fujian 351100 China

Fujian Provincial Center for Cardiovascular Medicine Fuzhou 350100 China

Cardiology Division Emory University School of Medicine 100 Woodruff Circle Atlanta GA 30322 USA

Beijing Tiantan Hospital China National Clinical Research Center for Neurological Diseases Advanced Innovation Center for Human Brain Protection Beijing Institute of Brain Disorders The Capital Medical University Beijing 100050 China

Funding

National Natural Science Foundation of China

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