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应用三维斑点追踪超声心动图评估肥胖患者左心功能障碍及循环外泌体 miRNA 的生物信息学分析

Evaluation of left ventricular dysfunction by three-dimensional speckle-tracking echocardiography and bioinformatics analysis of circulating exosomal miRNA in obese patients.

机构信息

Clinical Medicine School, Ningxia Medical University, Yinchuan, Ningxia, 750004, China.

Department of Cardiac Function Examination of Heart Centre, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, China.

出版信息

BMC Cardiovasc Disord. 2023 Sep 11;23(1):450. doi: 10.1186/s12872-023-03502-6.

DOI:10.1186/s12872-023-03502-6
PMID:37697228
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10496196/
Abstract

BACKGROUND

Obesity is an independent risk factor for cardiovascular disease and affects the human population. This study aimed to evaluate left ventricular (LV) dysfunction in obese patients with three-dimensional speckle-tracking echocardiography (3D-STE) and investigate the possible related mechanisms at the exosomal miRNA level.

METHODS

In total, 43 participants (16 obese patients and 27 healthy volunteers) were enrolled. All subjects underwent full conventional echocardiography as well as 3D-STE. Characterization and high-throughput sequencing for the isolated circulating exosomes and the differentially expressed miRNAs (DEMs) were screened for target gene prediction and enrichment analysis.

RESULTS

Obese patients had significantly lower global longitudinal strain (GLS) (-20.80%±3.10% vs. -14.77%±2.05%, P < 0.001), global circumferential strain (GCS) (-31.63%±3.89% vs. -25.35%±5.66%, P = 0.001), global radial strain (GRS) (43.21%±4.89% vs. 33.38%±3.47%, P < 0.001), and indexed LV end-diastolic volume (LVEDV) [38.07mL/m (27.82mL/m-9.57mL/m) vs. 24.79mL/m (21.97mL/m-30.73mL/m), P = 0.002] than healthy controls. GLS (ρ = 0.610, P < 0.001), GCS (ρ = 0.424, P = 0.005), and GRS (ρ = -0.656, P < 0.001) indicated a moderate relationship with body mass index (BMI). In obese patients, 33 exosomal miRNAs were up-regulated and 26 exosomal miRNAs were down-regulated when compared to healthy controls (P < 0.05). These DEMs possibly contribute to obesity-associated LV dysfunction through the PI3K-Akt signaling pathway. Important miRNAs, including miR-101-3p, miR-140-3p, and miR-99a-5p, have clinical utility in predicting early obesity-related myocardial injury.

CONCLUSIONS

The global strain obtained from 3D-STE can sensitively detect the decrease in LV myocardial function in obese patients. Key miRNAs and pathways provide a new theoretical basis and targets of action for studying obesity-induced LV dysfunction.

TRIAL REGISTRATION

In accordance with the World Health Organization (WHO) definition of a clinical trial, this study does not include human health-related interventions. This study was carried out at the General Hospital of Ningxia Medical University after obtaining institutional ethical approval (KYLL-2022-0556) and written informed consent from all participants.

摘要

背景

肥胖是心血管疾病的独立危险因素,影响着人类群体。本研究旨在通过三维斑点追踪超声心动图(3D-STE)评估肥胖患者的左心室(LV)功能障碍,并探讨外泌体 miRNA 水平上可能的相关机制。

方法

共纳入 43 名参与者(16 名肥胖患者和 27 名健康志愿者)。所有受试者均接受了全面的常规超声心动图和 3D-STE 检查。对分离的循环外泌体进行特征描述和高通量测序,并筛选差异表达 miRNA(DEMs)进行靶基因预测和富集分析。

结果

肥胖患者的整体纵向应变(GLS)(-20.80%±3.10% vs. -14.77%±2.05%,P<0.001)、整体圆周应变(GCS)(-31.63%±3.89% vs. -25.35%±5.66%,P=0.001)、整体径向应变(GRS)(43.21%±4.89% vs. 33.38%±3.47%,P<0.001)和左心室舒张末期容积指数(LVEDV)[38.07mL/m(27.82mL/m-9.57mL/m) vs. 24.79mL/m(21.97mL/m-30.73mL/m),P=0.002]均显著低于健康对照组。GLS(ρ=0.610,P<0.001)、GCS(ρ=0.424,P=0.005)和 GRS(ρ=-0.656,P<0.001)与体重指数(BMI)呈中度相关。与健康对照组相比,肥胖患者的 33 种外泌体 miRNA 上调,26 种外泌体 miRNA 下调(P<0.05)。这些 DEMs 可能通过 PI3K-Akt 信号通路导致肥胖相关的 LV 功能障碍。重要的 miRNA,包括 miR-101-3p、miR-140-3p 和 miR-99a-5p,在预测早期肥胖相关心肌损伤方面具有临床应用价值。

结论

3D-STE 获得的整体应变能够敏感地检测肥胖患者 LV 心肌功能的下降。关键的 miRNA 和途径为研究肥胖诱导的 LV 功能障碍提供了新的理论依据和作用靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5623/10496196/8ade8bdfadad/12872_2023_3502_Fig7_HTML.jpg
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