Age-dependent defective TGF-beta1 signaling in patients undergoing coronary artery bypass grafting.
BACKGROUND
Transforming growth factor beta (TGF-β1) is a pleiotropic cytokine, which is deregulated in atherosclerosis; however the role of age in this process is unknown. We aimed to assess whether TGF-β1 signaling is affected by age.


METHODS
Vascular smooth muscle cells (VSMC) were obtained from patients undergoing abdominal surgery. Levels of TGF-β1 were measured by ELISA in sera from 169 patients undergoing coronary artery bypass grafting (CABG). The p27 expression was determined by Western blot from internal mammary arteries (IMA) obtained from CABG patients (n=13). In VSMC from these patients undergoing abdominal surgery, secretion of TGF-β1 was determined by ELISA of cell-conditioned media.


RESULTS
In VSMC from aged patients we observed a lower TGF-β1 secretion, measured as TGF-β1 concentration in cell conditioned medium (p<0.001). This effect was correlated to an age-dependent decrease of p27 expression in IMA from aged CABG patients. In a similar manner, there was an age-dependent decrease of serum TGF-β1 levels in CABG patients (p=0.0195).


CONCLUSIONS
VSMC from aged patients showed a higher degree of cellular senescence and it was associated to a lower TGF-β1 secretion and signaling.
Santiago
S
Redondo
Jorge
J
Navarro-Dorado
Marta
M
Ramajo
Úrsula
Ú
Medina
Pedro
P
Molina-Sanchez
Zaady
Z
Garces
Mauricio
M
García-Alonso
Fernando
F
Reguillo
Enrique
E
Rodriguez
Vicente
V
Andres
Department of Pharmacology, School of Medicine, Universidad Complutense de Madrid, Av, Complutense s/n, 28040 Madrid, Spain. teje@med.ucm.es.
Teresa
T
Tejerina
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood* / Q000473:pathology; D015153:Blotting, Western; D002478:Cells, Cultured; D001026:Coronary Artery Bypass; D003324:Coronary Artery Disease / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008323:Mammary Arteries / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D018809:Proliferating Cell Nuclear Antigen; D053773:Transforming Growth Factor beta1; C413374:p27 antigen