靶向肾周脂肪中Top1的微小RNA-24-3p参与原发性醛固酮增多症患者的循环炎症及高心血管疾病风险。

MicroRNA-24-3p targeting Top1 in perirenal fat is involved in circulating inflammation and high cardiovascular disease risk in patients with primary aldosteronism.

作者信息

Li Xuelin, Luo Min, Zeng Yanmei, Zhang Renyi, Lin Xiaochun, Du Yuejun, Zhao Wei, Feng Qijian, Wu Minghai, Zhang Jin, Guo Lei, Wu Peili, Yang Chuyi, Cai Feifei, Wang Yuan, Hu Yuxuan, Wang Huiyun, Liu Nannan, Xu Lingling, Guan Meiping

机构信息

Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

Department of Endocrinology, Shenzhen Hospital, Southern Medical University, Shenzhen, China.

出版信息

J Transl Med. 2025 Mar 18;23(1):345. doi: 10.1186/s12967-025-06329-1.

DOI:10.1186/s12967-025-06329-1

PMID:40102901

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11916988/

Abstract

CONTEXT

Patients with primary aldosteronism (PA) are at a high risk of cardiovascular diseases (CVD) and metabolic syndrome. Notable inflammatory and fibrotic changes and differential microRNA (miRNA) expression profiles in the perirenal fat observed in PA may contribute to this increased risk, however, which has not been fully elucidated.

OBJECTIVE

This study aimed to explore the role of high expression of miR-24-3p in perirenal fat in circulating inflammation and its correlation with a high risk of CVD in patients with PA.

METHODS

Perirenal fat thickness (PRFT) measured by computed tomography (CT), miR-24-3p expression in perirenal fat, circulating inflammatory factors from adrenal veins and peripheral blood in patients with PA were analyzed. In vitro, white and brown adipocytes with miR-24-3p overexpression or inhibition respectively were stimulated with aldosterone and a unidirectional co-culture model of adipocytes and HUVEC was established. The target genes of miR-24-3p were identified.

RESULTS

Patients with PA and CVD have significantly higher PRFT than those without CVD. The expression level of miR-24-3p in perirenal fat was significantly positively correlated with PRFT. MiR-24-3p was significantly upregulated in the perirenal fat of PA and was associated with increased adipogenesis, inflammation, and oxidative stress, correlating with plasma aldosterone concentration (PAC), PRFT, cardiac remodeling, and weight gain. The IL-6 level in the peripheral blood was elevated in patients with PA and CVD, and the affected adrenal vein had the highest IL-6 level. Targeting Top1, miR-24-3p modulated aldosterone-induced effects in adipocytes and influenced IL-6 secretion, thereby affecting HUVEC.

CONCLUSION

The upregulation of miR-24-3p in the perirenal fat induced inflammation and oxidative stress by targeting Top1, which may contribute to a high risk of CVD in patients with PA.

摘要

背景

原发性醛固酮增多症（PA）患者患心血管疾病（CVD）和代谢综合征的风险很高。PA患者肾周脂肪中显著的炎症和纤维化改变以及差异微小RNA（miRNA）表达谱可能导致了这种风险增加，然而，这一点尚未完全阐明。

目的

本研究旨在探讨肾周脂肪中miR-24-3p高表达在循环炎症中的作用及其与PA患者CVD高风险的相关性。

方法

分析通过计算机断层扫描（CT）测量的肾周脂肪厚度（PRFT）、PA患者肾周脂肪中miR-24-3p的表达、肾上腺静脉和外周血中的循环炎症因子。在体外，分别用醛固酮刺激过表达或抑制miR-24-3p的白色和棕色脂肪细胞，并建立脂肪细胞与HUVEC的单向共培养模型。鉴定miR-24-3p的靶基因。

结果

患有PA和CVD的患者的PRFT显著高于未患CVD的患者。肾周脂肪中miR-24-3p的表达水平与PRFT显著正相关。miR-24-3p在PA患者的肾周脂肪中显著上调，并与脂肪生成增加、炎症和氧化应激相关，与血浆醛固酮浓度（PAC）、PRFT、心脏重塑和体重增加相关。PA和CVD患者外周血中的IL-6水平升高，受影响的肾上腺静脉中IL-6水平最高。通过靶向Top1，miR-24-3p调节醛固酮诱导的脂肪细胞效应并影响IL-6分泌，从而影响HUVEC。