Higher Circulating miR-199a-5p Indicates Poor Aerobic Exercise Capacity and Associates With Cardiovascular Dysfunction During Chronic Exposure to High Altitude

• Published in: Frontiers in physiology 2021-02, Vol.12, p.587241-587241
• Main Authors: Huang, He, Xie, Shenwei, Gu, Xiaolan, Xiang, Bin, Zhong, Zhifeng, Huang, Pei, Gao, Yuqi, Li, Peng
• Format: Article
• Language: English
• Subjects: biomarker; cardiovascular dysfunction; circulating microRNA; exercise capacity; hypoxia; miR-199a-5p; Physiology
• ISSN: 1664-042X; 1664-042X
• DOI: 10.3389/fphys.2021.587241

Hypoxia-induced decline in exercise capacity is ubiquitous among lowlanders who immigrated to high altitudes, which severely reduces their work efficiency and quality of life. Although studies have revealed that hypoxia-induced cardiovascular dysfunction limits exercise capacity at high altitudes, the mechanisms have not been well explored at the molecular level. miR-199a-5p is hypoxia-sensitive and serves as an important regulator in cardiovascular pathophysiology. However, whether miR-199a-5p is involved in cardiovascular dysfunction at high altitudes and contributes to subsequent reductions in exercise capacity remains unknown. Thus, this study aimed at exploring these relationships in a high altitude population. A total of 175 lowlanders who had immigrated to an altitude of 3,800 m 2 years previously participated in the present study. The level of plasma miR-199a-5p and the concentration of serum myocardial enzymes were detected by qRT-PCR and ELISA, respectively. Indices of cardiovascular function were examined by echocardiography. The exercise capacity was evaluated by Cooper's 12-min run test and the Harvard Step Test. Furthermore, we explored the biological functions of miR-199a-5p with silico analysis and a biochemical test. The level of miR-199a-5p was significantly higher in individuals with poor exercise capacity at 3,800 m, compared with those with good exercise capacity ( < 0.001). miR-199a-5p accurately identified individuals with poor exercise capacity (AUC = 0.752, < 0.001). The level of miR-199a-5p was positively correlated with cardiovascular dysfunction indices (all, < 0.001). Furthermore, miR-199a-5p was involved in the oxidative stress process. In this study, we reported for the first time that the level of circulating miR-199a-5p was positively associated with exercise capacity during chronic hypoxia at high altitudes. Moreover, higher miR-199a-5p was involved in hypoxia-induced cardiovascular dysfunctions, thus contributing to poorer exercise endurance at high altitudes.