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); membranetype 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.

Background and Purpose Plasma matrix metalloproteinase (MMP)-9 levels predict post-tissue plasminogen activator (tPA) hemorrhage. Methods: The authors investigated the effect of Minocycline on plasma MMP-9 in acute ischemic stroke in the MINOS trial and a comparison group. Results MMP-9 level decreased at 72 hours compared to baseline in MINOS (tPA, p=0.0022; non-tPA, p=0.0066), and was lower than in the non-MINOS comparison group at 24 hours (tPA, p<0.0001; non-tPA, p=0.0019). Conclusions Lower plasma MMP-9 was seen among tPA treated subjects in the MINOS trial. Combining Minocycline with tPA may prevent the adverse consequences of thrombolytic therapy via suppression of MMP-9 activity.