Fernando Reguillo

Human Vascular Smooth Muscle Cells From Diabetic Patients Are Resistant to Induced Apoptosis Due to High Bcl-2 Expression

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 7β-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.

Early recurrence is a predictor of late failure in surgical ablation of atrial fibrillation

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.

Relationship between serum levels of triglycerides and vascular inflammation, measured as COX-2, in arteries from diabetic patients: a translational study

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.

Role of TGF-β1 and MAP Kinases in the Antiproliferative Effect of Aspirin in Human Vascular Smooth Muscle Cells

Background We aimed to test the antiproliferative effect of acetylsalicylic acid (ASA) on vascular smooth muscle cells (VSMC) from bypass surgery patients and the role of transforming growth factor beta 1 (TGF-β1). Methodology/Principal Findings VSMC were isolated from remaining internal mammary artery from patients who underwent bypass surgery. Cell proliferation and DNA fragmentation were assessed by ELISA. Protein expression was assessed by Western blot. ASA inhibited BrdU incorporation at 2 mM. Anti-TGF-β1 was able to reverse this effect. ASA (2 mM) induced TGF-β1 secretion; however it was unable to induce Smad activation. ASA increased p38MAPK phosphorylation in a TGF-β1-independent manner. Anti-CD105 (endoglin) was unable to reverse the antiproliferative effect of ASA. Pre-surgical serum levels of TGF-β1 in patients who took at antiplatelet doses ASA were assessed by ELISA and remained unchanged. Conclusions/Significance In vitro antiproliferative effects of aspirin (at antiinflammatory concentration) on human VSMC obtained from bypass patients are mediated by TGF-β1 and p38MAPK. Pre-surgical serum levels of TGF- β1 from bypass patients who took aspirin at antiplatelet doses did not change.

Validación del EuroSCORE II: ¿funciona en nuestro medio?

a b s t r a c t Objectives: Validate the new EuroSCORE (ESII) risk model in terms of discriminative and calibration power and compare this results with the classic EuroSCORE (ES).We also compare our data distribution with the ESII database. Methods: A 4166 patient population operated during a 7 year period was analyzed. The model was then tested on the validation data set for calibration (by comparing the observed and predicted mortality) and for discrimination (using the area under the ROC curve). Results: The predicted mortality by the ESII was higher than the ES: 9.1(SD: 10.4) vs 3.46 (SD: 4.3): p<0.001. The Hosmer-Lemeshow test showed a poor calibration for both models: ES (x 2 =26.6, p=<0.001),ESII (x 2 =58.19, p<0.0001). Areas under ROC curves were 0.75 (IC95% 0.72-0.78) for ES and 0.78 (IC95% 0.75-0.81) for ESII (p<0.233). Conclusions: The new EuroSCORE II risk model has a predicted mortality lower than EuroSCORE and a good predictive value in terms of calibration and poor discrimination. A non significant better discrimination power was observer in the ESII. The distribution of some variables was different between our data and ESII.

Age-dependent defective TGF-beta1 signaling in patients undergoing coronary artery bypass grafting

BackgroundTransforming 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.MethodsVascular 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.ResultsIn 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).ConclusionsVSMC from aged patients showed a higher degree of cellular senescence and it was associated to a lower TGF-β1 secretion and signaling.

Decreased pre-surgical CD34+/CD144+ cell number in patients undergoing coronary artery bypass grafting compared to coronary artery disease-free valvular patients

BackgroundCardiovascular disease has been linked to endothelial progenitor cell (EPC) depletion and functional impairment in atherosclerosis and aortic stenosis. EPCs may play a pivotal role in vascular grafting. However, the EPC depletion in coronary artery bypass grafting (CABG) patients has not been compared to coronary artery disease-free valvular replacement patients with aortic stenosis.MethodsWe aimed to assess the basal number of CD34+/KDR+ and CD34+/CD144+ cells in CABG patients, compared to aortic stenosis valvular replacement patients. 100 patients (51 CABG and 49 valvular surgery ones) were included in the present study. All CABG or valvular patients had angiographic demonstration of the presence or the absence of coronary artery disease, respectively. Numbers of CD34+/KDR+ and CD34+/CD144+ were assessed by flow cytometry of pre-surgical blood samples.ResultsWe found a lower number of CD34+/CD144+ cells in CABG patients compared to valvular patients (0.21 ± 0.03% vs. 0.47 ± 0.08%), and this difference remained statistically significant after the P was adjusted for multiple comparisons (P = 0.01428). Both groups had more EPCs than healthy controls.ConclusionsPre-surgical CD34+/CD144+ numbers are decreased in CABG patients, compared to valvular patients with absence of coronary disease.

Off-Pump to On-Pump Emergency Conversion: Incidence, Risk Factors, and Impact on Short- and Long-Term Results.

Emergency conversion to on‐pump during off‐pump coronary artery bypass surgery (CABG) increases morbidity and mortality. We analyze its risk factors and impact on short‐ and long‐term outcomes.

Reoperation for composite valve graft failure: Operative results and midterm survival

The replacement of a failed composite valve graft is technically more demanding and is associated with increased morbidity and mortality. We present our technique and outcomes for reoperations for composite graft failures.

Embolectomía en una embolia pulmonar aguda masiva

Presentamos el caso de un varon de 57 anos que, en el seno de un meningioma microcitico, padece una tromboembolia pulmonar masiva aguda con inestabilidad hemodinamica. Dado el riesgo de hemorragia por el tumor craneal, se contraindica la terapia fibrinolitica y se procede a practicar embolectomia pulmonar. Esta se realiza bajo anestesia general, con canulacion convencional y bajo hipotermia moderada. Se extrae embolo en el tronco de la arteria pulmonar y con cateter de Fogarty se extraen embolos en ramas lobares y segmentarias. Discutimos la asociacion de enfermedad tromboembolica con determinadas neoplasias y el tratamiento de la tromboembolia pulmonar