Matrix metalloproteinase-2 and -9 exacerbate arterial stiffening and angiogenesis in diabetes and chronic kidney disease
| Autor: | H.H. Clarice Yang, Adeera Levin, Genevieve Brin, Ada W.Y. Chung, William A. Gourlay, Elliott Chum, Mhairi K. Sigrist |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Adult
Male medicine.medical_specialty Physiology Angiogenesis Phosphates Cohort Studies chemistry.chemical_compound Risk Factors Physiology (medical) Internal medicine Diabetes mellitus medicine Humans Diabetic Nephropathies Endothelial dysfunction Pulse wave velocity Angiostatins Aged Neovascularization Pathologic business.industry Arteries Middle Aged medicine.disease Elasticity Vascular endothelial growth factor Endocrinology medicine.anatomical_structure chemistry Matrix Metalloproteinase 9 Cardiovascular Diseases Case-Control Studies Circulatory system Chronic Disease Matrix Metalloproteinase 2 Female Kidney Diseases Cardiology and Cardiovascular Medicine business Kidney disease Artery |
| Zdroj: | Cardiovascular research. 84(3) |
| ISSN: | 1755-3245 |
| Popis: | Aims Chronic kidney disease (CKD) and diabetes are the prominent risk factors of cardiovascular disease (CVD). Matrix metalloproteinase (MMP)-2 and -9 regulate vascular structure by degrading elastic fibre and inhibit angiogenesis by generating angiostatin. We hypothesized that MMP-2 and -9 were up-regulated in the arterial vasculature from CKD patients with diabetes, compared with those without diabetes. Methods and results During living donor transplantation procedures, arteries from donors ( n = 8) and recipients (non-diabetic, n = 8; diabetic, n = 8; matched in age, gender, and dialysis treatments) were harvested. Diabetic arteries had increased MMP-2 and -9 activities by 42 and 116% compared with non-diabetic ones. Diabetic arteries were the stiffest, and the stiffness measurement was highly correlated with the summation of MMP-2 + MMP-9 activities ( r = 0.738, P = 0.0002). Pulse wave velocity measurements correlated with MMP activity ( r = 0.683, P = 0.005). Elastic fibre degradation and calcification were worst in diabetic vessels. The phosphate level, which was 25% higher in diabetic patients, correlated with MMP activity ( r = 0.513, P = 0.04) and in vitro stiffness ( r = 0.545, P = 0.03), respectively. Angiostatin expression was doubled, whereas vascular endothelial growth factor was 50% reduced in diabetic compared with non-diabetic vessels. Microvascular density in diabetic vessels was 48% of that in non-diabetic ones, and it was strongly associated with MMP activity ( r = −0.792, P < 0.0001) and vasorelaxation ( r = 0.685, P = 0.0009). Conclusion Using a matched case–control design, we report up-regulation of MMP-2 and -9 in diabetic CKD arteries and correlate those with stiffening, impaired angiogenesis, and endothelial dysfunction. These findings may help to explain the high susceptibility of CVD in diabetic and non-diabetic CKD patients. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|