| Title: | Leptin Aggravates Thoracic Aortic Dissection Through Impairment of Energy Metabolism in Nrip2+ Smooth Muscle Cells |
| Journal: | Advanced Science |
| Published: | 16 Jul 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40667784/ |
| DOI: | https://doi.org/10.1002/advs.202502027 |
Publication 16165
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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.</p>
19 Authors
- 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
1 Application
| Application ID | Title |
|---|---|
| 84352 | Exploring the novel risk factors and therapeutic targets of cardiovascular disease and the role of cardiovascular health in health-related outcomes |
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