Abstract
BackgroundHypoxia-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.MethodsA 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.ResultsThe 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 (p < 0.001). miR-199a-5p accurately identified individuals with poor exercise capacity (AUC = 0.752, p < 0.001). The level of miR-199a-5p was positively correlated with cardiovascular dysfunction indices (all, p < 0.001). Furthermore, miR-199a-5p was involved in the oxidative stress process.ConclusionIn 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.
Highlights
IntroductionWith the rapid development of the economy, millions of lowlanders (such as the Chinese Han) have immigrated to high altitude regions (elevation: ≥2,500 m) for work, construction, and military operations
With the rapid development of the economy, millions of lowlanders have immigrated to high altitude regions for work, construction, and military operations
The poor exercise capacity (PEC) group had a higher value of mean pulmonary artery pressure (mPAP) (21.32 ± 2.39 mmHg vs. 18.17 ± 2.18 mmHg, p < 0.001, Cohen’s d = 1.377), and RV-Tei (0.24 ± 0.04 vs. 0.19 ± 0.03, p < 0.001, Cohen’s d = 1.414) compared with the good exercise capacity (GEC) group, but no difference was found in left ventricular systolic or diastolic function
Summary
With the rapid development of the economy, millions of lowlanders (such as the Chinese Han) have immigrated to high altitude regions (elevation: ≥2,500 m) for work, construction, and military operations. During exposure to high altitude regions, hypoxia-induced decline in exercise capacity is ubiquitous among them, which severely reduces their work efficiency and quality of life (Kayser, 2013; Chatterjee et al, 2017). The mechanisms involved in cardiovascular dysfunction and decreased exercise capacity at high altitudes have not been well explored at the molecular level. 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. 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. This study aimed at exploring these relationships in a high altitude population
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