Evidence for a Matrix Metalloproteinase Induction/Activation System in Arterial Vasculature and Decreased Synthesis and Activity in Diabetes
- 1University of Georgia College of Pharmacy, Medical College of Georgia, Augusta, Georgia
- 2Department of Surgery, Medical College of Georgia, Augusta, Georgia
- 3Vascular Biology Center, Medical College of Georgia, Augusta, Georgia
Abstract
Pathological remodeling characterized by extracellular matrix (ECM) deposition contributes to the diabetic vascular complications. Matrix metalloproteinases (MMPs) regulate ECM turnover. However, the expression profile of the MMP system in diabetic human tissue remains unknown. The objectives of this study were 1) to identify a local MMP induction/activation system that exists in arterial vasculature and 2) to determine how the MMP system may be altered in diabetes. Internal mammary artery specimens were obtained from patients who did (n = 14) and did not (n = 14) have diabetes and were undergoing coronary artery bypass grafting surgery. ECM inducer protein (EMMPRIN); membrane-type MMP (MT-MMP); and MMP-1, -2, and -9 were quantified by immunoblotting and densitometric scanning (pixels). Pro-MMP-1 and MMP-2 levels were decreased from 952 ± 120 and 1,081 ± 508 pixels, respectively, in nondiabetic tissue to 398 ± 62 and 249 ± 42 pixels in the diabetic tissue (P < 0.05). Both EMMPRIN and MT-MMP expression and total MMP activity were decreased by twofold in diabetic patients (P < 0.05). These results demonstrated for the first time that an MMP induction and activation system exists in human arterial vasculature and that it is downregulated in diabetes. Decreased MMP activity may contribute to increased collagen deposition and pathological remodeling in diabetes.
Footnotes
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Address correspondence and reprint requests to Adviye Ergul, MD, Medical College of Georgia, Clinical Pharmacy CJ-1020, 1120 15th Street, Augusta, GA 30912. E-mail: aergul{at}mail.mcg.edu.
Received for publication 18 February 2002 and accepted in revised form 26 June 2002.
ECM, extracellular matrix; EMMPRIN, extracellular matrix metalloproteinase inducer protein; IMA, internal mammary artery; MMP, matrix metalloproteinase; MT-MMP, membrane-type matrix metalloproteinase; TIMP, tissue inhibitor of matrix metalloproteinase.
- DIABETES
