The role of matrix metalloproteinases in diabetes mellitus

Diabetes mellitus (DM) is a leading risk factor for cardiovascular disease that adversely affects multiple vascular components from early in its course. Current evidence implicates matrix metalloproteinases (MMPs) and their endogenous inhibitors in diverse pathways associated with the development and progression of diabetic microvascular complications. In diabetic nephropathy, altered MMPs expression contributes to extracellular matrix deposition and glomerular hypertrophy that eventually lead to proteinuria and renal insufficiency. In diabetic cardiomyopathy, MMPs participate in the breakdown of collagen and elastin, myocardial remodelling as well as the vulnerability of the coronary plaque. The development of diabetic peripheral arterial disease is mediated by the impaired angiogenesis caused by the activity of MMPs. Experimental data support an integral role of MMPs in cerebral circulation and stroke volume in diabetes. An excess of MMPs may contribute in poor diabetic wound healing. Future research should further clarify the role of MMPs within the pathophysiological substrate of diabetes, as well as potential therapeutic options. © 2012 Bentham Science Publishers

Soluble receptor for advanced glycation end-product levels are related to albuminuria and arterial stiffness in essential hypertension

Background and aims: Emerging evidence suggests that the soluble receptor for advanced glycation end-products (sRAGE) is implicated in the development of vascular disease. We investigated the interrelationships of sRAGE with albumin to creatinine ratio (ACR) and arterial stiffness in essential hypertension. Methods and results: In 309 untreated non-diabetic hypertensives, ACR values were determined as the mean of three non-consecutive morning spot urine samples and aortic stiffness was evaluated on the basis of carotid to femoral pulse wave velocity (c-f PWV). In all subjects, venous blood sampling was performed for the estimation of sRAGE levels. Patients with low (n = 155) compared to those with high sRAGE values (n = 154) had greater 24-h systolic BP (140 ± 8 vs. 134 ± 7 mmHg, p < 0.0001), exhibited higher ACR (36.3 ± 51.6 vs. 17.2 ± 1.2 mg g-1, p < 0.0001) and c-f PWV (8.3 ± 1.5 vs. 7.8 ± 1.1 m s-1, p = 0.003), independently of confounding factors. Multiple regression analyses revealed that age, male sex, 24-h systolic BP and sRAGE were the 'independent correlates' of ACR (R2 = 0.493, p < 0.0001), while age, 24-h systolic BP and sRAGE were the 'independent correlates' of c-f PWV (R2 = 0.428, p < 0.0001). Conclusion: In hypertensives, decreased sRAGE levels are accompanied by pronounced albuminuria and arterial stiffening. The association of sRAGE with ACR and c-f PWV suggests involvement of sRAGE in the progression of hypertensive vascular damage. © 2011 Elsevier B.V