Effect of glycated collagen on proliferation of human smooth muscle cells in vitro

Abstract

While non-enzymatic glycation of long-lived tissue proteins such as collagen has been implicated in chronic complications of diabetes mellitus, its role in the aetiology of diabetic macroangiopathy has not been elucidated. To test the hypothesis that glycation of collagen abolishes the inhibitory effect of native collagen on the proliferation of human smooth muscle cells, we obtained smooth muscle cells from human gastric arteries and cultured them on dishes coated with glycated or non-glycated collagen. The proliferation of human smooth muscle cells in the presence of 10% fetal calf serum or platelet derived growth factor-BB (10 ng/ml) was inhibited by type 1 collagen coated on the dishes. Glycation of collagen with glucose 6-phosphate for 7 days abolished the growth-inhibitory effect of native collagen. Succinylation of collagen, which like glycation blocked the lysyl residues in collagen, also abolished the growth-inhibitory effect. Adhesion of human smooth muscle cells to collagen-coated dishes was not affected by glycation of collagen. Addition of glycated albumin to the medium did not affect the growth of human smooth muscle cells on plastic dishes. The inhibition of human smooth muscle cell proliferation by collagen was not reversed by the glycation of collagen in the presence of aminoguanidine. Results suggest that early glycation abolishes the inhibitory effect of collagen on human smooth muscle cell proliferation and may thus participate in the progression of macro-angiopathy in diabetes.

Oleate, not ligands of the receptor for advanced glycation end-products, promotes proliferation of human arterial smooth muscle cells

“…In other studies, AGE-BSA did not stimulate proliferation of pig or rabbit SMCs [42,43]. The lack of effects of AGEs on human SMCs is consistent with results of a previous study using BSA incubated for 1 week in 20 mmol/l glucose-6-phosphate [44].…”

Advanced Glycation End Product Interventions Reduce Diabetes-Accelerated Atherosclerosis

“…However, interpretation of these findings remains speculative because this difference between agents was not noted for all collagen subtypes. In addition, AGEs have been shown to induce the proliferation (46) and activation of vascular smooth muscle cells (47) to produce fibrillar collagen. This is supported in the present study by the amelioration of diabetes-induced ␣-SMA expression by each of the AGE reducing treatments.…”

Endothelial Adhesion Molecule Expression Is Enhanced in the Aorta and Internal Mammary Artery of Diabetic Patients

“…The observation that intimal hyperplasia is established in the transplant vessel prior to its surgical relocation is consistent with an increased risk for restenosis following coronary bypass surgery seen in diabetic patients [45,46]. The enhanced proliferation of human smooth muscle cells cultured from diabetic patients has been attributed to a variety of factors including an increased sensitivity to T-cell stimulation [47], increased D-glucose uptake [48], insulin [49], AGEs [50], and glycated collagen [51]. T-lymphocytes and glycated proteins were both observed in the present study.…”