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.
Highlights
IntroductionThrombospondin-1 (THBS1), expressed in various cells like endothelial cells, vascular smooth muscle cells (VSMCs), and cardiomyocytes, elevates dramatically under conditions of hypoxia [1]
In Cohort 1, the age and body mass index (BMI) did not differ significantly between the patients and controls (p > 0.05) while they were significant in Cohort 2 study groups (p < 0.05)
The systolic blood pressure (SBP) and diastolic blood pressure (DBP), and as a consequence, mean arterial pressure (MAP) was significantly elevated in patients as compared to the controls of both the cohorts (p < 0.0001)
Summary
Thrombospondin-1 (THBS1), expressed in various cells like endothelial cells, vascular smooth muscle cells (VSMCs), and cardiomyocytes, elevates dramatically under conditions of hypoxia [1]. THBS1, belongs to the thrombospondin (THBS) family consisting of five multifunctional glycoproteins, namely THBS1–5. THBS1 and 2 have been studied the most and are described in cell–cell interactions, apoptosis and as antiangiogenic agents [2]. THBS1 functions mainly through its receptor CD47 [3]; the other receptors are involved [4]. The functions of markedly induced levels of THBS1 are confirmed within the tumor microenvironment [5] and in cardiovascular disorders [3]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
