B-type natriuretic peptide, vascular endothelial growth factor, endothelin-1, and nitric oxide synthase in chronic mountain sickness

Abstract

The pathogenesis of chronic mountain sickness (CMS) may involve vasoactive peptides. The aim of this study was to investigate associations between CMS and levels of B-type natriuretic peptide (BNP), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), and endothelial nitric oxide synthase (eNOS). A total of 24 patients with CMS and 50 control subjects residing at 4,300 m participated in this study. Mean pulmonary arterial pressure (mPAP) was measured by echocardiography. Serum BNP, VEGF, ET-1, and eNOS were measured. Receiver operator characteristic curves to assess the balance of sensitivity and specificity for CMS were constructed. As a result, patients with CMS had significantly greater mPAP compared with controls and had lower arterial O(2) saturation (Sa(O(2))). Both BNP and ET-1 correlated positively with mPAP and negatively with Sa(O(2)), whereas serum VEGF levels were inversely correlated with Sa(O(2)); eNOS correlated negatively with mPAP and positively with Sa(O(2)). Median concentrations of BNP were greater in patients with CMS compared with those without CMS: 369 pg/ml [interquartile range (IQR) = 336-431] vs. 243 pg/ml (IQR = 216-279); P < 0.001. Similarly, concentrations of VEGF [543 pg/ml (IQR = 446-546) vs. 243 pg/ml (IQR = 216-279); P < 0.001] and ET-1 [14.7 pg/ml (IQR = 12.5-17.9) vs. 11.1 pg/ml (IQR = 8.7-13.9); P = 0.05] were higher in those with CMS compared with those without, whereas eNOS levels were lower in those with CMS [8.90 pg/ml (IQR 7.59-10.8) vs. 11.2 pg/ml (9.13-13.1); P < 0.001]. The areas under the receiver operator characteristic curves for diagnosis of CMS were 0.91, 0.93, 0.77, and 0.74 for BNP, VEGF, ET-1, and eNOS, respectively. In age- and biomarker-adjusted logistic regression, BNP and VEGF were positively predictive of CMS, whereas eNOS was inversely predictive. In conclusion, severe chronic hypoxemia and consequent pulmonary hypertension in patients with CMS may stimulate release of natriuretic peptides and angiogenic cytokines. These vasoactive peptides may play an important role in the pathogenesis and clinical expression of CMS and may indicate potential prognostic factors in CMS that could serve as targets for therapeutic trials or clinical decision making.

Left ventricular adaptation to high altitude: speckle tracking echocardiography in lowlanders, healthy highlanders and highlanders with chronic mountain sickness

“…It is noteworthy that relative hypoventilation with more severe hypoxemia and marked polycythemia also had no deleterious effects on LV function in maladapted highlanders with CMS. This finding was unexpected as excessive hemoglobin concentration can be detrimental to cardiovascular and endothelial function through elevated blood viscosity [41][42][43][44] and, accordingly, is thought to predispose to premature cardiovascular disease [45]. The preserved LV function in CMS subjects in our study may be explained by compensatory mechanisms, such as autonomic adaptation.…”

The Local HIF-2α/EPO Pathway in the Bone Marrow is Associated with Excessive Erythrocytosis and the Increase in Bone Marrow Microvessel Density in Chronic Mountain Sickness

“…Angiogenesis might be a compensatory process in high-altitude residents that occurs to alleviate hypoxia in microcirculation and it may also be involved in the pathophysiology of CMS (Appenzeller et al, 2003;Ge et al, 2011;Buroker et al, 2012Buroker et al, , 2013Espinoza et al, 2014). The bone marrow is the primary site of angiogenesis and is a readily accessible tissue for the investigation of angiogenesis.…”

Vascular Endothelial Growth Factor as a Prognostic Parameter in Subjects with “Plateau Red Face”

“…The pathogenesis of PRF is not clear and it could involve multiple factors. It is generally believed that exposure to extreme environmental stresses, such as hypoxia, cold weather, and strong ultraviolet light can lead to increased blood flow near the skin surface due to dilation of blood capillaries (Penaloza and Arias-Stella 2007;Ge et al 2011).…”

“…Serum samples were stored in liquid nitrogen for analysis. Serum VEGF was measured with an enzyme linked immunosorbent assay (ELISA) kit (D&R system), which was described previously (Ge et al, 2011). This assay was calibrated against highly purified recombinant human VEGF 165.…”