Abstract

Endothelial cell senescence promoting endothelial dysfunction has been suggested to contribute to the development of age-related vascular disorders. Senescence is characterized by an irreversible cell cycle arrest involving the p53/p21 pathway and oxidative stress. The present study has evaluated the level of vascular senescence and oxidative stress in internal mammary artery segments from 20 aged patients undergoing bypass surgery with or without risk factors including hypertension and diabetes. Patients were 60 to 85 years old. After removal, the internal mammary artery segment was incubated in a physiological salt solution, transported at room T°C to the laboratory and processed within 3 h. Segments were cleaned of fat and connective tissues and cut into rings of 3-4 mm length. Rings were then embedded in OCT tissue Tek, stored at -80°C for subsequent analysis. Senescence markers were assessed by immunofluorescence staining, and the level of oxidative stress using the redox-sensitive probe dihydroethidine in 14 μm sections. In normotensive and non-diabetic patients, a low level of both oxidative stress and p53 and p21 was observed throughout the arterial wall including the endothelium and neointima. These markers were increased in sections of hypertensive patients and was most pronounced in hypertensive and diabetic patients. The present findings indicate that oxidative stress and senescence are observed in the internal mammary artery of aged patients and that these effects are more pronounced in patients with risk factors including hypertension and diabetes.

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