Secreted protein acidic and rich in cysteine (SPARC), also known as BM-40, is expressed in various cell types, with exceptionally high levels found in adipocytes. The expression of SPARC levels increases during embryonic development, gradually decreasing in normal adult tissues. However, during inflammation, tissue damage, and remodeling, its expression increases again, reflecting its crucial role in tissue regeneration and repair [1,2] and making it a potential new candidate marker for early injury detection. The levels of SPARC have been reported positively correlated with human BMI, inflammatory marker C-reactive protein, and macrophage migration inhibitory factor (MIF) [3,4]. SPARC levels are also elevated in patients with acute liver failure or with acute antagonistic alcoholic hepatitis [5]. In type 2 diabetes mellitus (T2DM), diabetic nephropathy, and gestational diabetes, elevated levels of SPARC are observed positively associated with hyperglycemia and insulin resistance [4,6,7]. In addition, SPARC expression is increased in the vitreous of patients with diabetic retinopathy [8]. Although these studies have examined the role of SPARC in various diseases linked to metabolic syndrome, there is a lack of clinical research on the relationship between SPARC and hypertension.

Aside from the clinical implications, recent studies suggest that SPARC actively participates in important pathophysiological processes, such as wound healing, angiogenesis, and inflammation [9], by facilitating cell-ECM interactions, ECM remodeling, and growth factor signaling pathway [10,11]. SPARC has an anti-angiogenic function by inhibiting the interaction of VEGF with endothelial cells or by regulating the expression of matrix metalloproteinases (MMPs) and TGF-β1 [[12], [13], [14]], and this effect was reversed in SPARC knockout mice [1,15]. In contrast, some cleavage products of SPARC are documented to stimulate angiogenesis [16]. Elevated SPARC expression in pulmonary hypertension appears to be specifically localized to the pulmonary vasculature, leading to pulmonary vascular remodeling [17]. Consistently, the knockdown of SPARC slows the progression of pulmonary hypertension [18].

Impaired endothelial function is the initiating factor in hypertension, yet little has been reported about its role in endothelial function beyond its essential function as an extracellular matrix glycoprotein and its role in vascular remodeling. In this study, we aim to explore the relevance of SPARC to hypertension and investigate its role in endothelium-dependent relaxation (EDR).