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 7␤-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. Diabetes 55: [1243][1244][1245][1246][1247][1248][1249][1250][1251] 2006

Population over 80 years who require surgery for degenerative aortic stenosis has largely increased in the past decades. We have compared short- and mid-term results for conventional aortic valve replacement (AVR) for calcific-degenerative aortic stenosis in older and younger than 80 years operated at our institution between April 2004 and December 2008. Predictors of mortality and major adverse cardio and cerebrovascular events (MACCEs) on the postoperative and follow-up period were determined through multivariable analysis. Four hundred and fifty-one patients were included in the study. Ninety-four (20.8%) were >or=80. Previous cardiac surgery [odds ratio (OR)=4.08, P=0.047], renal failure (OR=6.75, P<0.001), concomitant coronary artery bypass grafting (CABG) (OR=2.57, P=0.034), female sex (OR=2.49, P=0.047), and severe pulmonary hypertension (OR=3.68, P=0.024) were independent predictors of in-hospital mortality. In the follow-up, age >or=80 years [Hazard ratio (HR)=2.44, P=0.02], high blood pressure (HBP) (HR=5.2, P=0.025) and peripheral arterial disease (PAD) (HR=5.1, P<0.001) were independent predictors for late mortality. Only PAD (HR=3.55, P=0.014) and HBP (HR=8.24, P=0.04) were independent predictors for late cardiac mortality. Renal failure (OR=2.57, P=0.005), severe pulmonary hypertension (OR=3.49, P=0.005) and concomitant CABG (OR=2.49, P=0.002) were independent predictors for postoperative MACCEs. Diabetes mellitus (HR=2.03, P=0.033) and PAD (HR=2.3, P=0.041) were independent predictors for MACCEs in the follow-up. According to these data, we can conclude that conventional open AVR for degenerative aortic stenosis grants good early- and mid-term outcomes in octogenarians in our experience.

We sought to determine if early recurrence of atrial fibrillation (AF) after surgical ablation is a risk factor of late failure. Between February 2004 to May 2009, 106 patients underwent surgical ablation of concomitant permanent AF with radiofrequency. Operations primarily consisted of valve surgery in 85% of patients. Hospital mortality was 2.8% (n = 3). The median follow-up was 37 months (interquartile rank 12-77), and was complete in 99% of patients. Freedom from AF was 82%, 76% and 68% at one, two and three years, respectively. Patients with early recurrence of AF had less prevalence of sinus rhythm in late follow-up (P < 0.001). Multivariate Cox regression analysis showed that AF duration [hazard ratio (HR) 1.014, 95% CI 1.009-1.020, P < 0.001] and early recurrence of AF (HR 3.45, 95% CI 1.50-7.95, P = 0.004) were independent risk factors for failure. In conclusion, in our series, early recurrence of AF after surgical ablation is a strong predictor of late failure.

BackgroundInflammation is a common feature in the majority of cardiovascular disease, including Diabetes Mellitus (DM). Levels of pro-inflammatory markers have been found in increasing levels in serum from diabetic patients (DP). Moreover, levels of Cyclooxygenase-2 (COX-2) are increased in coronary arteries from DP.MethodsThrough a cross-sectional design, patients who underwent CABG were recruited. Vascular smooth muscle cells (VSMC) were cultured and COX-2 was measured by western blot. Biochemical and clinical data were collected from the medical record and by blood testing. COX-2 expression was analyzed in internal mammary artery cross-sections by confocal microscopy. Eventually, PGI2 and PGE2 were assessed from VSMC conditioned media by ELISA.ResultsOnly a high glucose concentration, but a physiological concentration of triglycerides exposure of cultured human VSMC derived from non-diabetic patients increased COX-2 expression .Diabetic patients showed increasing serum levels of glucose, Hb1ac and triglycerides. The bivariate analysis of the variables showed that triglycerides was positively correlated with the expression of COX-2 in internal mammary arteries from patients (r2 = 0.214, P < 0.04).ConclusionsWe conclude that is not the glucose blood levels but the triglicerydes leves what increases the expression of COX-2 in arteries from DP.

Aims/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 from diabetic 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.