The association of SPARC with hypertension and its function in endothelial-dependent relaxation

Background and aims: Secreted protein acidic and rich in cysteine (SPARC) is involved in the pathological processes of many metabolic diseases. However, studies on the relevance of SPARC to hypertension and its involvement in endothelial function are scarce. In this study, we aim to explore the relevance of SPARC to hypertension and investigate its role in endothelium-dependent relaxation (EDR). Methods: 110 patients who met the criteria were recruited as participants. Serum SPARC concentrations were determined by Luminex assay. The correlation between SPARC levels and hypertension was analyzed. After treatment with SPARC ex vivo or in vivo, endothelial-dependent relaxation (EDR) was measured by wire myography. Western blotting was performed to detect the expression of proteins relevant to endothelial function. Results: Our results showed that serum SPARC levels were significantly higher in the hypertensive group and were positively associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP). Functional results demonstrated that SPARC dramatically impaired EDR and induced the excess production of reactive oxygen species (ROS) in endothelial cells. Further experimental results confirmed that SPARC reduced angiotensin-converting enzyme 2 (ACE2) expression and ACE2 overexpression or activation completely abolished the impairing effect of SPARC on endothelial function. Conclusions: The present study reveals the correlation between elevated SPARC and hypertension and confirms its adverse effect on endothelial function, helping establish a comprehensive understanding of hypertension-related endothelial dysfunction in a new scope.