National Clinical Research Center for Metabolic Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, 410000, China.
Department of Metabolism and Endocrinology, General Hospital of Northern Theater Command, Shenyang, 110016, China.
Cardiovasc Diabetol. 2024 Sep 9;23(1):331. doi: 10.1186/s12933-024-02404-x.
Visceral adipose tissue in individuals with obesity is an independent cardiovascular risk indicator. However, it remains unclear whether adipose tissue influences common cardiovascular diseases, such as atherosclerosis, through its secreted exosomes.
The exosomes secreted by adipose tissue from diet-induced obesity mice were isolated to examine their impact on the progression of atherosclerosis and the associated mechanism. Endothelial apoptosis and the proliferation and migration of vascular smooth muscle cells (VSMCs) within the atherosclerotic plaque were evaluated. Statistical significance was analyzed using GraphPad Prism 9.0 with appropriate statistical tests.
We demonstrate that adipose tissue-derived exosomes (AT-EX) exacerbate atherosclerosis progression by promoting endothelial apoptosis, proliferation, and migration of VSMCs within the plaque in vivo. MicroRNA-132/212 (miR-132/212) was detected within AT-EX cargo. Mechanistically, miR-132/212-enriched AT-EX exacerbates palmitate acid-induced endothelial apoptosis via targeting G protein subunit alpha 12 and enhances platelet-derived growth factor type BB-induced VSMC proliferation and migration by targeting phosphatase and tensin homolog in vitro. Importantly, melatonin decreases exosomal miR-132/212 levels, thereby mitigating the pro-atherosclerotic impact of AT-EX.
These data uncover the pathological mechanism by which adipose tissue-derived exosomes regulate the progression of atherosclerosis and identify miR-132/212 as potential diagnostic and therapeutic targets for atherosclerosis.
肥胖个体的内脏脂肪组织是独立的心血管风险指标。然而，脂肪组织是否通过其分泌的外泌体影响动脉粥样硬化等常见心血管疾病仍不清楚。
从饮食诱导肥胖小鼠的脂肪组织中分离出外泌体，以研究其对动脉粥样硬化进展的影响及其相关机制。评估了内皮细胞凋亡以及动脉粥样硬化斑块内血管平滑肌细胞（VSMC）的增殖和迁移。使用 GraphPad Prism 9.0 软件和适当的统计检验进行统计显著性分析。
我们证明脂肪组织来源的外泌体（AT-EX）通过促进体内斑块内皮细胞凋亡、增殖和 VSMC 迁移，加剧动脉粥样硬化进展。在 AT-EX 货物中检测到 microRNA-132/212（miR-132/212）。在机制上，富含 miR-132/212 的 AT-EX 通过靶向 G 蛋白亚单位 alpha 12 加剧了软脂酸诱导的内皮细胞凋亡，并通过靶向体外的磷酸酶和张力蛋白同源物增强了血小板衍生生长因子 BB 诱导的 VSMC 增殖和迁移。重要的是，褪黑素降低了外泌体 miR-132/212 水平，从而减轻了 AT-EX 的促动脉粥样硬化作用。
这些数据揭示了脂肪组织来源的外泌体调节动脉粥样硬化进展的病理机制，并确定 miR-132/212 是动脉粥样硬化的潜在诊断和治疗靶点。
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