Folic acid administration reduces neointimal thickening, augments neo-vasa vasorum formation and reduces oxidative stress in saphenous vein grafts from pigs used as a model of diabetes

• Published in: Diabetologia Vol. 53; no. 5; pp. 980 - 988
• Main Authors: Bloor, J., Shukla, N., Smith, F. C. T., Angelini, G. D., Jeremy, J. Y.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01-05-2010; Springer; Springer Nature B.V
• Subjects: Acids; Analysis of Variance; Animals; Biological and medical sciences; Blood Glucose; Carotid Arteries - drug effects; Carotid Arteries - pathology; Carotid Arteries - surgery; Clinical trials; Coronary vessels; Diabetes; Diabetes Mellitus, Experimental - pathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Endothelium, Vascular - drug effects; Endothelium, Vascular - pathology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Folic Acid - administration & dosage; Glucose; Heart surgery; Hogs; Homocysteine; Human Physiology; Hyperglycemia; Hypotheses; Internal Medicine; Laboratory animals; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Nitric oxide; Oxidative stress; Oxidative Stress - drug effects; Plasma; Saphenous Vein - drug effects; Saphenous Vein - pathology; Saphenous Vein - transplantation; Smooth muscle; Statistics, Nonparametric; Swine; Tunica Intima - drug effects; Tunica Intima - pathology; Vasa Vasorum - drug effects; Vasa Vasorum - pathology; Vascular Patency - drug effects; Veins & arteries; Vitamin B; United Kingdom > UK; Type 2 diabetes; Vein graft; Oxidative stress; Neointima; Folic acid; Endocrinopathy; Vitamin; Metabolic diseases; Pig; Micronutrient; Vertebrata; Mammalia; Saphenous vein; Animal; Graft; Models; Artiodactyla; Ungulata; Thickening
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-010-1680-5

Aims/hypothesis
There is evidence that plasma homocysteine augments vein graft failure and that it augments both micro- and macro-angiopathy in patients with diabetes mellitus. It is therefore suggested that homocysteine may augment vein graft thickening, a major cause of vein graft failure, in diabetic patients, as well as impairing adaptive growth of a new vasa vasorum, possibly through overproduction of superoxide. In order to test these proposals, the effect of folic acid administration, which lowers plasma homocysteine, on vein graft thickening and microvessel density was studied in pigs used as a model of diabetes.
Methods
Non-ketotic hyperglycaemia was induced in Landrace pigs by intravenous injection of streptozotocin, and folic acid was fed daily for 1 month. Vein grafts were excised and the thickness of the neointima and media and microvessel density were assessed by planimetry and superoxide formation.
Results
Plasma total homocysteine was significantly reduced by folic acid in both control and diabetic pigs, whereas glucose was unchanged. Compared with controls, diabetic pigs showed increased neointimal thickness and superoxide formation and decreased adventitial microvessel density. Folic acid reduced neointimal thickness and superoxide formation and augmented microvessel density in diabetic but not in control pigs.
Conclusions
Folic acid administration reduces neointimal thickening, augments vasa vasorum neoformation and reduces oxidative stress in saphenous vein grafts from diabetic pigs. Folic acid may therefore be particularly effective in reducing vein graft failure in diabetic patients.