Abstract
Background: Extracellular matrix metalloproteinase inducer (EMMPRIN; CD147) is a transmembrane glycoprotein that stimulates the production of matrix metalloproteinases (MMPs). These MMPs mediate vascular remodeling and are considered biomarkers for cardiovascular risk. The activity of CD147 depends mainly on its glycosylation, which varies significantly among different conditions. However, it is unclear if CD147 glycosylation or its role in MMP upregulation is influenced by the diabetic milieu characterized by high glucose levels and abundant glycation end products (AGEs). In this study, we sought to investigate the differential expression and glycosylation levels of CD147 in obese, diabetic (OB-T2D) individuals compared to non-OB controls. Methods: Blood and adipose tissue (AT) samples were obtained from OB-T2D individuals and controls (n=40, each). DEXA scanning was used for body composition analyses. Flow-induced dilation (FID) was assessed in vivo in the brachial artery and ex vivo in AT-isolated arterioles. Other cardiometabolic risk factors related to glucose and lipid metabolism and systemic inflammation were measured. Results: Circulating CD147 was considerably greater in OB individuals, mirroring the glycosylated CD147 and the N-acetylglucosaminyltransferase, MGAT5 protein levels in the AT. Within the OB-T2D group, AT and circulating CD147 correlated with higher body mass index, total and visceral fat percentage, fasting plasma glucose and insulin, insulin resistance measurement (HOMA-IR), glycosylated hemoglobin, systolic BP, and plasma levels of MMP2/9, AGEs (Carboxymethyl lysine and methyl-glyoxal-lysine dimer), C-reactive protein, interleukin 6, and tumor necrosis factor-alpha. AT-arteriolar FID was significantly lower in the OB-T2D individuals across all pressure gradients, while carotid pulse wave velocity (PWV) was higher, indicating arterial stiffness. CD147 correlated negatively with brachial artery and AT-arteriolar FID and flow-induced nitric oxide production and positively with PWV. Conclusion: Our findings imply that vascular dysfunction in OB-T2D patients is linked to higher levels of CD147 and its glycosylated fraction, which in turn is associated with other cardiometabolic risk factors.
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