Abnormal growth regulation of vascular smooth muscle cells by heparin in patients with restenosis.
Proliferation of vascular smooth muscle cells (VSMC) underlies myointimal hyperplasia, which can lead to restenosis after angioplasty and vascular surgery. We propose that some individuals have an intrinsic capacity for this exaggerated response to vascular injury, partly through decreased sensitivity to the physiological growth inhibitor heparin. We investigated the effect of heparin on VSMC from restenotic lesions and from apparently normal vessels of the same patients, and VSMC from control patients undergoing primary bypass procedures. Cells from patients with restenosis (both restenotic lesion and undiseased vein) showed much lower sensitivity to growth inhibition by heparin than the controls (median inhibition 8 [95% Cl -2 to 25] vs 22 [15-44]%, p < 0.001); this finding suggests aberrant growth regulation in these cells.
Chan
P
P
Department of Clinical Pharmacology, St Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London, UK.
Patel
M
M
Betteridge
L
L
Munro
E
E
Schachter
M
M
Wolfe
J
J
Sever
P
P
D001157:Arterial Occlusive Diseases / Q000503:physiopathology / Q000601:surgery; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003251:Constriction, Pathologic; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D012008:Recurrence
D006493:Heparin