Circulating Microparticles Are Differentially Increased in Lowlanders and Highlanders with High Altitude Induced Pulmonary Hypertension during the Cold Season.

The role of microparticles (MPs) and cold in high altitude pulmonary hypertension (HAPH) remains unexplored. We investigated the impact of long-term cold exposure on the pulmonary circulation in lowlanders and high-altitude natives and the role of MPs. Pulmonary hemodynamics were evaluated using Doppler echocardiography at the end of the colder and warmer seasons. We further examined the miRNA content of MPs isolated from the study participants and studied their effects on human pulmonary artery smooth muscle (hPASMCs) and endothelial cells (hPAECs). Long-term exposure to cold environment was associated with an enhanced pulmonary artery pressure in highlanders. Plasma levels of CD62E-positive and CD68-positive MPs increased in response to cold in lowlanders and HAPH highlanders. The miRNA-210 expression contained in MPs differentially changed in response to cold in lowlanders and highlanders. MPs isolated from lowlanders and highlanders increased proliferation and reduced apoptosis of hPASMCs. Further, MPs isolated from warm-exposed HAPH highlanders and cold-exposed highlanders exerted the most pronounced effects on VEGF expression in hPAECs. We demonstrated that prolonged exposure to cold is associated with elevated pulmonary artery pressures, which are most pronounced in high-altitude residents. Further, the numbers of circulating MPs are differentially increased in lowlanders and HAPH highlanders during the colder season.

Pulmonary Vascular Pressure Response to Acute Cold Exposure in Kyrgyz Highlanders.

Background/Aims: Long-term high altitude residence leads to a sustained increase in pulmonary vascular resistance and elevation of pulmonary artery pressure due to chronic alveolar hypoxia. However, living at high altitude is also associated with other environmental factors such as cold. There is still little experimental evidence suggesting detrimental effects of low temperatures on the pulmonary vasculature. Therefore, our objective was to investigate acute effects of cold exposure on the pulmonary circulation in Kyrgyz high altitude natives. Methods: Responses of the pulmonary circulation during acute exposure to controlled cold conditions (4°C-6°C) for 60 minutes were measured in highlanders using Doppler echocardiography. Based on the Doppler echocardiography-derived tricuspid regurgitant systolic pressure gradient (TRG), subjects with TRG ≥40 mmHg were allocated into the pulmonary hypertension (PH) group. Participants from the PH group were compared with volunteer control subjects with TRG <40 mmHg. All baseline measurements were evaluated in a warm room during 60 minutes (22°C-28°C). Following baseline echocardiography, the subjects were assigned to either warm or cold exposure for an additional 60 minutes. Results: Acute cold exposure significantly increased TRG both in the control (ΔTRG, 4.93 mmHg) and in the PH (ΔTRG, 8.15 mmHg) group, compared to the respective warm exposure conditions (ΔTRG, -0.14 and -0.05 mmHg). No changes in cardiac output were observed upon cold exposure. Conclusion: Thus, acute exposure to cold leads to elevation of pulmonary artery pressure in high altitude residents.