Department of Geriatrics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, 200080, Shanghai, China.
Department of Cardiology, Changhai Hospital, Naval medical University, 168 Changhai Road, 200433, Shanghai, China.
Herz. 2023 Aug;48(4):301-308. doi: 10.1007/s00059-022-05121-x. Epub 2022 Jun 8.
Hyperlipidemia is a major risk factor for vascular endothelial injury and atherosclerosis leading to cardiovascular diseases. Early diagnosis of vascular endothelial injury is important for the prevention and prognosis of cardiovascular diseases. This study aimed to investigate sensitive circulating microRNA (miRNA) as a potential diagnostic biomarker of vascular endothelial injury in a hyperlipidemic rat model.
The miRNA expression profile was detected by miRNA microarray. The hyperlipidemic rat model was established by intraperitoneal injection of vitamin D combined with a high-fat diet. Plasma miRNA levels were measured by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR).
No significant difference was found in the types of highly expressed miRNAs between human umbilical artery endothelial cells (HUAEC) and human umbilical vein endothelial cells (HUVEC). A total of 10 highly expressed miRNAs in endothelial cells were selected as candidate miRNAs, including miR-21, miR-126, let-7a, miR-23a, miR-221, miR-125b, miR-26a, miR-29a, miR-16, and miR-100. The plasma levels of let-7a, miR-126, miR-21, and miR-26a were significantly elevated in hyperlipidemic rats at 30 and 50 days after modeling, while the plasma level of miR-29a was significantly decreased. No significant change was found in the plasma levels of miR-125b, miR-23a, miR-221, miR-100, and miR-16. Interestingly, a significant reduction in plasma miR-29 level was detected as early as 20 days after modeling, which was earlier than for soluble intercellular adhesion molecule‑1 (sICAM-1).
The plasma levels of endothelial cell-enriched miRNAs were correlated with vascular endothelial injury induced by hyperlipidemia. miR-29a might serve as a potential early diagnostic biomarker of endothelial injury-related diseases.
高血脂是导致血管内皮损伤和动脉粥样硬化从而引发心血管疾病的主要危险因素。早期诊断血管内皮损伤对于预防和预测心血管疾病具有重要意义。本研究旨在探讨敏感的循环微小 RNA（miRNA）作为高血脂大鼠模型血管内皮损伤的潜在诊断生物标志物。
采用 miRNA 微阵列检测 miRNA 表达谱。通过腹腔注射维生素 D 联合高脂饮食建立高血脂大鼠模型。采用定量逆转录聚合酶链反应（qRT-PCR）检测血浆 miRNA 水平。
人脐静脉内皮细胞（HUVEC）和人脐动脉内皮细胞（HUAEC）中高表达 miRNA 的类型无明显差异。共选择 10 种在内皮细胞中高表达的 miRNA 作为候选 miRNA，包括 miR-21、miR-126、let-7a、miR-23a、miR-221、miR-125b、miR-26a、miR-29a、miR-16 和 miR-100。建模后 30 和 50 天，高血脂大鼠血浆中 let-7a、miR-126、miR-21 和 miR-26a 的水平显著升高，而 miR-29a 的水平显著降低。miR-125b、miR-23a、miR-221、miR-100 和 miR-16 的血浆水平无明显变化。有趣的是，建模后 20 天即可检测到血浆 miR-29 水平显著降低，早于可溶性细胞间黏附分子 1（sICAM-1）。
富含内皮细胞的血浆 miRNA 水平与高血脂引起的血管内皮损伤相关。miR-29a 可能作为内皮损伤相关疾病的潜在早期诊断生物标志物。
