title: Human vascular smooth muscle cells from diabetic patients are resistant to induced apoptosis due to high Bcl-2 expression.
abstract: An emerging body of evidence suggests that vascular remodeling in diabetic patients involves a perturbation of the balance between cell proliferation and cell death. Our aim was to study whether arteries and vascular smooth muscle cells (VSMCs) isolated from diabetic patients exhibit resistance to apoptosis induced by several stimuli. Internal mammary arteries (IMAs) were obtained from patients who had undergone coronary artery bypass graft surgery. Arteries from diabetic patients showed increasing levels of Bcl-2 expression in the media layer, measured by immunofluorescence and by Western blotting. Human IMA VSMCs from diabetic patients showed resistance to apoptosis, measured as DNA fragmentation and caspase-3 activation, induced by C-reactive protein (CRP) and other stimuli, such as hydrogen peroxide and 7beta-hydroxycholesterol. The diabetic cells also exhibited overexpression of Bcl-2. Knockdown of Bcl-2 expression with Bcl-2 siRNA in cells from diabetic patients reversed the resistance to induced apoptosis. Consistent with the above, we found that pretreatment of nondiabetic VSMCs with high glucose abolished the degradation of Bcl-2 induced by CRP. Moreover, cell proliferation was increased in diabetic compared with nondiabetic cells. This differential effect was potentiated by glucose. We conclude that the data provide strong evidence that arterial remodeling in diabetic patients results from a combination of decreased apoptosis and increased proliferation.
authors.affiliation: Department of Pharmacology, School of Medicine, Universidad Complutense, 28040 Madrid, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Ruiz
authors.forename: Antonio
authors.initials: A
authors.lastname: Gordillo-Moscoso
authors.forename: Eugenia
authors.initials: E
authors.lastname: Padilla
authors.forename: Santiago
authors.initials: S
authors.lastname: Redondo
authors.forename: Enrique
authors.initials: E
authors.lastname: Rodriguez
authors.forename: Fernando
authors.initials: F
authors.lastname: Reguillo
authors.forename: Ana M
authors.initials: AM
authors.lastname: Briones
authors.forename: Cornelis
authors.initials: C
authors.lastname: van Breemen
authors.forename: Elena
authors.initials: E
authors.lastname: Okon
authors.forename: Teresa
authors.initials: T
authors.lastname: Tejerina
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D003094:Collagen / Q000032:analysis; D003331:Coronary Vessels / Q000473:pathology / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000235:genetics / Q000503:physiopathology / Q000601:surgery*; D004549:Elastin / Q000032:analysis; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007387:Internal Mammary-Coronary Artery Anastomosis; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000503:physiopathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D008353:Mannitol; D003094:Collagen; D004549:Elastin; D005947:Glucose