RT Journal Article
T1 Overproduction of cyclo-oxygenase-2 (COX-2) is involved in the resistance to apoptosis in vascular smooth muscle cells from diabetic patients: a link between inflammation and apoptosis
A1 Redondo Salvo, Santiago
A1 Ruiz, Eliseo
A1 Gordillo-Moscoso, Antonio
A1 Ramajo, M.
A1 Rodríguez, Estefanía
A1 Carnero, M.
A1 Casado, Martín
A1 Tejerina Sánchez, María Teresa
A1 Navarro Dorado, Jorge
A1 Reguillo Lacruz, Fernando José
AB AbstractAims/hypothesis Inflammation is a common feature in cardiovascular diseases, including diabetes mellitus. In addition to the well-known inflammatory role of cyclooxygenase-2 (COX-2), this protein has also been implicated in apoptosis resistance in tumour cells. Vascular smooth muscle cells (VSMC) from diabetic patients are also resistant to apoptosis because of an increased abundance of B cell lymphoma 2 protein (BCL2). In this work, we investigated whether overproduction of COX-2 was involved in the resistance to apoptosis in VSMC fromdiabetic patients.Methods VSMC were obtained from internal mammary arteries from patients who had undergone coronary artery bypass graft surgery. Apoptosis was measured by DNA fragmentation, BCL2 degradation and cytochrome c release.Results Apoptosis induced by C-reactive protein in cells from non-diabetic patients was mediated by COX-2. VSMC from diabetic patients showed higher basal levels of COX-2 compared with those from non-diabetic patients. Transfection of VSMC from non-diabetic patients with a plasmid containing COX-2 (also known as PTGS2) increased basal production of COX-2 and BCL2 and mimicked the resistance to apoptosis that occurs in diabetic patients. We also found a significant correlation (R=0.846, p=0.016) between COX-2 and BCL2 production in arterial rings from diabetic patients measured by confocal microscopy. However, inhibition of COX-2 production by small interfering RNA proved unable to reverse BCL2 production in diabetic VSMC.Conclusions/interpretation These results suggest a link between inflammation (COX-2) and apoptosis resistance (BCL2) in the arteries of diabetic patients. This relationship is not causative and the common production of these two proteins may be co-regulated by shared regulatory elements in diabetes.
PB Springer
SN 0012-186X
SN 1432-0428
YR 2010
FD 2010-10-19
LK https://hdl.handle.net/20.500.14352/100575
UL https://hdl.handle.net/20.500.14352/100575
LA eng
NO Redondo S, Ruiz E, Gordillo-Moscoso A, Navarro-Dorado J, Ramajo M, Rodríguez E, Reguillo F, Carnero M, Casado M, Tejerina T. Overproduction of cyclo-oxygenase-2 (COX-2) is involved in the resistance to apoptosis in vascular smooth muscle cells from diabetic patients: a link between inflammation and apoptosis. Diabetologia. 2011 Jan;54(1):190-9. doi: 10.1007/s00125-010-1947-x. Epub 2010 Oct 19. PMID: 20957341.
DS Docta Complutense
RD 21 abr 2025