Matrix metalloproteinases and diabetic vascular complications.
Diabetes mellitus (DM) is associated with an increased incidence of cardiovascular events and microvascular complications. These complications contribute to the morbidity and mortality associated with DM. There is increasing evidence supporting a role for matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of matrix metalloproteinases - TIMPs) in the atherosclerotic process. However, the relationship between MMPs/TIMPs and diabetic angiopathy is less well defined. Hyperglycemia directly or indirectly (eg, via oxidative stress or advanced glycation products) increases MMP expression and activity. These changes are associated with histologic alterations in large vessels. On the other hand, low proteolytic activity of MMPs contributes to diabetic nephropathy. Within atherosclerotic plaques an imbalance between MMPs and TIMPs may induce matrix degradation, resulting in an increased risk of plaque rupture. Furthermore, because MMPs enhance blood coagulability, MMPs and TIMPs may play a role in acute thrombotic occlusion of vessels and consequent cardiovascular events. Some drugs can inhibit MMP activity. However, the precise mechanisms involved are still not defined. Further research is required to demonstrate the causative relationship between MMPs/TIMPs and diabetic atherosclerosis. It also remains to be established if the long-term administration of MMP inhibitors can prevent acute cardiovascular events.
Kadoglou
Nikolaos P
NP
Department of Vascular Surgery, Athens University Medical School, Athens, Greece. nikoskad@yahoo.com
Daskalopoulou
Stella S
SS
Perrea
Despina
D
Liapis
Christos D
CD
D001161:Arteriosclerosis / Q000503:physiopathology*; D002318:Cardiovascular Diseases / Q000503:physiopathology; D003324:Coronary Artery Disease / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000503:physiopathology; D017127:Glycation End Products, Advanced / Q000502:physiology; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology; D020782:Matrix Metalloproteinases / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology; D012307:Risk Factors; D019714:Tissue Inhibitor of Metalloproteinases / Q000502:physiology*
D017127:Glycation End Products, Advanced; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases