Hypertensive Patients Exhibit Enhanced Thrombospondin-1 Levels at High-Altitude

Abstract

Thrombospondin-1 (THBS1) levels elevate under hypoxia and have relevance in several cardiovascular disorders. The association of THBS1 with endothelial dysfunction implies its important role in hypertension. To establish the hypothesis, we screened patients with hypertension and their respective controls from the two different environmental regions. Cohort 1 was composed of Ladakhis, residing at 3500 m above sea level (ASL), whereas Cohort 2 was composed of north-Indians residing at ~200 m ASL. Clinical parameters and circulating THBS1 levels were correlated in the case–control groups of the two populations. THBS1 levels were significantly elevated in hypertension patients of both cohorts; however, the levels were distinctly enhanced in the hypertensive patients of HA as compared to normoxia (p < 0.002). The observation was supported by the receiver operating curve analysis with an area under curve of 0.7007 (0.627–0.774) demonstrating the discriminatory effect of hypobaric hypoxia on the levels as compared to normoxia (p < 0.011). Significant correlation of THBS1 and mean arterial pressure was observed with upraised positive correlations in the hypertensive highlanders as compared to the hypertensive patients from sea-level. The prevalence of differential distribution of THBS1 and CD47 genes variants, their interactions, and association with the THBS1 levels were also determined. Genotype-interactions between THBS1 rs2228263 and CD47 rs9879947 were relevant and the regression analysis highlighted the association of risk genotype-interactions with increased THBS1 levels in hypertension. Genetic studies of additional thrombospondin pathway-related genes suggest the complex role of THBS1 in the presence of its family members and the related receptor molecules at HA.

Role of CD93 in Health and Disease

“…Regarding the SNPs of CD93, it has been reported that the SNP rs2749812 of CD93 was associated with a significantly higher cardiovascular risk [ 61 ] and the presence of hypertension at high-altitudes [ 118 ], while the SNP rs3746731 of CD93 gene was also associated with an increased risk of developing coronary heart disease after adjustment for hypertension, diabetes mellitus, BMI, plasma HDL cholesterol and plasma triglyceride levels [ 24 ].…”

Thrombospondin-1 associated with carotid intima–media thickness among individuals with hypertension

“…Studies have demonstrated that TSP-1 is associated with various vascular risk factors for CVDs. 6,16,18 Increased TSP-1 levels have also been noted in patients 16 and rats with hypertension. 24 Studies have also reported that TSP-1 may represent a link between vascular risk factors and vascular atherosclerotic lesion development .…”

“…TSP-1 is associated with various conventional vascular risk factors for CVD, such as diabetes, 6 hypertension, 16 hypercholesterolemia, 17 and obesity. 18 Because both TSP-1 and vascular risk factors are involved in arterial injury pathogenesis, understanding whether these vascular risk factors can modulate TSP-1 and regulate the pathological process of carotid atherosclerosis is vital.…”

Yth m6A RNA-Binding Protein 1 Regulates Osteogenesis of MC3T3-E1 Cells under Hypoxia via Translational Control of Thrombospondin-1

“…THBS1 is known as a glycoprotein and also acts as an endogenous angiogenesis inhibitor [ 34 ]. THBS1 level dramatically elevates under hypoxia and is implicated in several cardiovascular disorders [ 35 ]. Previous studies have shown that THBS1 is associated with endothelial dysfunction by inducing the onset of inflammatory responses, and is involved in platelet aggregation and adhesion to endothelial cells [ 36 ].…”