Abstract
CD147 is a glycoprotein that stimulates the production of matrix metalloproteinases (MMPs), known contributors to cardiovascular risk. The activity of CD147 protein depends on its glycosylation. However, it is unclear whether CD147 protein expression or glycosylation are influenced by the diabetic milieu characterized by hyperglycemia and abundant glycation-end-products (AGEs). We examined the circulating and visceral adipose tissue (VAT) levels of CD147 and their correlation with vascular function in obese, obese diabetic, and non-obese controls (n = 40, each). The circulating levels of CD147 and the glycosylated CD147 protein in VAT were considerably higher in obese, particularly obese diabetic subjects compared to controls. Obese diabetics had the lowest brachial and arteriolar vasoreactivity and the highest carotid pulse-wave velocity (PWV, a measure of arterial stiffness) among the three groups. CD147 correlated positively with body mass index (BMI), total and visceral fat mass, PWV, and plasma levels of glucose, insulin, MMPs, and AGEs and negatively with brachial artery and VAT-arteriolar vasoreactivity and nitric oxide production. Multivariate regression revealed that BMI, body fat mass, insulin, and glucose levels significantly predicted CD147. Our data suggest that higher levels of CD147 in obese subjects, particularly those with diabetes, are linked to vascular dysfunction and several cardiometabolic risk factors.
Highlights
Diabetes is a global epidemic with a growing healthcare impact
On the other hand, fasting plasma insulin (FPI) and the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) differed considerably among the three groups, with the highest levels observed in obese T2D participants
Diabetes is characterized by hyperglycemia, which causes metabolic stress and cellular injury partly due to the generation of compounds such as abundant glycation-endproducts (AGEs) [14,25]
Summary
There is a wellestablished link between diabetes and an increased risk of developing cardiovascular disease (CVD) [1]; significant pathophysiological mechanisms have yet to be identified. Previous studies have reported a contributing role of matrix metalloproteinases (MMPs) to the development of hypertension and CVDs such as atherosclerosis [2]. The expression and activity of these extracellular remodeling enzymes have been shown to increase in atherosclerotic plaques [3] and in patients with hypertension, coronary artery diseases, and myocardial infarction [2]. The proteins that regulate MMPs are prospective therapeutic targets with the potential to lower cardiovascular risk and need further exploration. CD147, known as extracellular matrix metalloproteinase inducer (EMMPRIN), is one of the essential MMP regulators, and it is critical to determine its potential role in the association between metabolic diseases and vascular dysfunction [4]
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