The fall in ambient oxygen pressure in high-altitude milieu elicits a wide range of physiological responses in the myocardium, which may differ from individual to individual. This condition, known as hypobaric hypoxia, invokes the cardioprotective heat shock response. The present study focuses on the role played by this ubiquitous response in mediating a differential tolerance to acute hypoxic stress. Sprague Dawley rats were exposed to simulated hypoxia equivalent to 223 mmHg pressure, screened on the basis of time taken for onset of a characteristic hyperventilatory response, and categorized as susceptible (25 min). The tolerant animals displayed a significant upregulation of heat shock protein (Hsp)70/HSPA, evident through immunohistochemical staining of the cardiac tissue. The increased expression of transcription factor heat shock factor-1 led to the downstream activation of other chaperones, including Hsp90/HSPC, Hsp60/HSPD1, and Hsp27/HSPB1. The higher induction of HSPs in tolerant animals contributed to higher nitric oxide synthesis mediated by both endothelial nitric oxide synthase and inducible nitric oxide synthase activation. Conversely, susceptible animals showed significantly higher expression of the proinflammatory markers tumor necrosis factor alpha and nuclear factor kappa-light-chain enhancer of activated B cells in the myocardium. Evaluation of circulatory stress markers identified increased levels of reactive oxygen species, corticosterone and endothelin-1 in the susceptible animals highlighting their vulnerability to hypoxic stress. The heat shock response, through the action of chaperones and enhanced NO generation thus contributes substantially to the ability to sustain survival under acute sub lethal hypoxia.

Cerebral and pulmonary syndromes may develop in unacclimatized individuals shortly after ascent to high altitude resulting in high altitude illness, which may occur due to extravasation of fluid from intra to extravascular space in the brain, lungs and peripheral tissues. The objective of the present study was to evaluate the potential of seabuckthorn (SBT) (Hippophae rhamnoidesL.) leaf extract (LE) in curtailing hypoxia‐induced transvascular permeability in the lungs by measuring lung water content, leakage of fluorescein dye into the lungs and further confirmation by quantitation of albumin and protein in the bronchoalveolar lavage fluid (BALF). Exposure of rats to hypoxia caused a significant increase in the transvascular leakage in the lungs. The SBT LE treated animals showed a significant decrease in hypoxia‐induced vascular permeability evidenced by decreased water content and fluorescein leakage in the lungs and decreased albumin and protein content in the BALF. The SBT extract was also able to significantly attenuate hypoxia‐induced increase in the levels of proinflammatory cytokines and decrease hypoxia‐induced oxidative stress by stabilizing the levels of reduced glutathione and antioxidant enzymes. Pretreatment of the extract also resulted in a significant decrease in the circulatory catecholamines and significant increase in the vasorelaxation of the pulmonary arterial rings as compared with the controls. Further, the extract significantly attenuated hypoxia‐induced increase in the VEGF levels in the plasma, BALF (ELISA) and lungs (immunohistochemistry). These observations suggest that SBT LE is able to provide significant protection against hypoxia‐induced pulmonary vascular leakage.

Several chronic diseases lead to skeletal muscle loss and a decline in physical performance. MicroRNAs (miRNAs) are small, noncoding RNAs, which have exhibited their role in the development and diseased state of the skeletal muscle. miRNA regulates gene expression by binding to the 3′ untranslated region of its target mRNA. Due to the robust stability in biological fluids, miRNAs are ideal candidate as biomarker. These miRNAs provide a novel avenue in strengthening our awareness and knowledge about the factors governing skeletal muscle functions such as development, growth, metabolism, differentiation, and cell proliferation. It also helps in understanding the therapeutic strategies in improving or conserving skeletal muscle health. This review outlines the evidence regarding the present knowledge on the role miRNA as a potential biomarker in skeletal muscle diseases and their exploration might be a unique and potential therapeutic strategy for various skeletal muscle disorders.