Thrombospondin 2 is a novel biomarker of essential hypertension and associated with nocturnal Na⁺ excretion and insulin resistance

ABSTRACT

Background

Thrombospondins (TSPs) play important roles in several cardiovascular diseases. However, the association between circulating (plasma) thrombospondin 2 (TSP2) and essential hypertension remains unclear. The present study was aimed to investigate the association of circulating TSP2 with blood pressure and nocturnal urine Na⁺ excretion and evaluate the predictive value of circulating TSP2 in subjects with hypertension.

Methods and Results

603 newly diagnosed essential hypertensive subjects and 508 healthy subjects were preliminarily screened, 47 healthy subjects and 40 newly diagnosed essential hypertensive subjects without any chronic diseases were recruited. The results showed that the levels of circulating TSP2 were elevated in essential hypertensive subjects. The levels of TSP2 positively associated with systolic blood pressure (SBP), diastolic blood pressure (DBP), and other clinical parameters, including homeostasis model assessment of insulin resistance (HOMA-IR), brachial-ankle pulse wave velocity, and serum triglycerides, but negatively associated with nocturnal urine Na⁺ concentration and excretion and high-density lipoprotein cholesterol. Results of multiple linear regressions showed that HOMA-IR and nocturnal Na⁺ excretion were independent factors related to circulating TSP2. Mantel–Haenszel chi-square test displayed linear relationships between TSP2 and SBP (χ² = 35.737) and DBP (χ² = 26.652). The area under receiver operating characteristic curve (AUROC) of hypertension prediction was 0.901.

Conclusion

Our study suggests for the first time that the circulating levels of TSP2 may be a novel potential biomarker for essential hypertension. The association between TSP2 and blood pressure may be, at least in part, related to the regulation of renal Na⁺ excretion, insulin resistance, and/or endothelial function.

GRAPHICAL ABSTRACT

KEYWORDS:

• Thrombospondin 2
• hypertension
• renal Na⁺ excretion
• insulin resistance
• endothelial function

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Conceptualization, Chunyan Deng and Jian Yang; Data curation, Longlong Zhang and Chunyan Deng; Formal analysis, Xiaoxin Zhou, Longlong Zhang and Xun Lei; Investigation, Xiaoxin Zhou and Longlong Zhang; Methodology, Xiaoxin Zhou; Resources, Longlong Zhang, Xiaoqian Lin, Xi Chen, Hong Liu, XiaYuan, Qiuxia Zhao and Weiwei Wang; Software, Xiaoxin Zhou; Supervision, Jian Yang; Validation, Jian Yang; Writing – original draft, Xiaoxin Zhou and Chunyan Deng; Writing – review & editing, Pedro A Jose and Jian Yang.

Data availability statement

The data presented in this study are available on request from the corresponding author. The data are not publicly available due to privacy.

Additional information

Funding

This work was supported in part by grants from the National Natural Science Foundation of China (82100459), the Scientific Research Innovation Project for Postgraduate in Chongqing (CYB22227), Program of Chongqing Medical University for Youth Innovation in Future Medicine (W0085), and Project of Chongqing Medical Talent Studio (2022).