Mechanism of endothelial dysfunction in apolipoprotein E-deficient mice

Endothelium-dependent relaxations mediated by NO are impaired in a mouse model of human atherosclerosis. Our objective was to characterize the mechanisms underlying endothelial dysfunction in aortas of apolipoprotein E (apoE)-deficient mice, treated for 26 to 29 weeks with a lipid-rich Western-type diet. Aortic rings from apoE-deficient mice showed impaired endothelium-dependent relaxations to acetylcholine (10(-)(9) to 10(-)(5) mol/L) and Ca(2+) ionophore (10(-)(9) to 10(-)(6) mol/L) and endothelium-independent relaxations to diethylammonium (Z)-1-(N,N-diethylamino)diazen-1-ium-1,2-diolate (DEA-NONOate, 10(-)(10) to 10(-)(5) mol/L) compared with aortic rings from C57BL/6J mice (P<0.05). By use of confocal microscopy of an oxidative fluorescent probe (dihydroethidium), increased superoxide anion (O(2)(-)) production was demonstrated throughout the aortic wall but mainly in smooth muscle cells of apoE-deficient mice. CuZn-superoxide dismutase (SOD) and Mn-SOD protein expressions were unaltered in the aorta exposed to hypercholesterolemia. A cell-permeable SOD mimetic, Mn(III) tetra(4-benzoic acid) porphyrin chloride (10(-)(5) mol/L), reduced O(2)(-) production and partially normalized relaxations to acetylcholine and DEA-NONOate in apoE-deficient mice (P<0.05). [(14)C]L-Citrulline assay showed a decrease of Ca(2+)-dependent NOS activity in aortas from apoE-deficient mice compared with C57BL/6J mice (P<0.05), whereas NO synthase protein expression was unchanged. In addition, cGMP levels were significantly reduced in the aortas of apoE-deficient mice (P<0.05). Our results demonstrate that in apoE-deficient mice on a Western-type fat diet, impairment of endothelial function is caused by increased production of O(2)(-) and reduced endothelial NO synthase enzyme activity. Thus, chemical inactivation of NO with O(2)(-) and reduced biosynthesis of NO are key mechanisms responsible for endothelial dysfunction in aortas of atherosclerotic apoE-deficient mice.     

Metabolic profile and cardiovascular risk factors among Latin American HIV-infected patients receiving HAART

ObjectiveDetermine the prevalence of metabolic abnormalities (MA) and estimate the 10-year risk for cardiovascular disease (CVD) among Latin American HIV-infected patients receiving highly active anti-retroviral therapy (HAART).MethodsA cohort study to evaluate MA and treatment practices to reduce CVD has been conducted in seven Latin American countries. Adult HIV-infected patients with at least one month of HAART were enrolled. Baseline data are presented in this analysis.ResultsA total of 4,010 patients were enrolled. Mean age (SD) was 41.9 (10) years; median duration of HAART was 35 (IQR: 10-51) months, 44% received protease inhibitors. The prevalence of dyslipidemia and metabolic syndrome was 80.2% and 20.2%, respectively. The overall 10-year risk of CVD, as measured by the Framingham risk score (FRF), was 10.4 (24.7). Longer exposure to HAART was documented in patients with dyslipidemia, metabolic syndrome and type 2 diabetes mellitus. The FRF score increased with duration of HAART. Male patients had more dyslipidemia, high blood pressure, smoking habit and higher 10-year CVD than females.ConclusionsTraditional risk factors for CVD are prevalent in this setting leading to intermediate 10-year risk of CVD. Modification of these risk factors through education and intervention programs are needed to reduce CVD.     

Percutaneous coronary intervention for iatrogenic occlusion of the circumflex artery after mitral anuloplasty

We describe a patient with obstruction of the dominant circumflex artery after surgical repair of the mitral valve, repaired successfully with percutaneous coronary intervention during the immediate postoperative period. We discuss the etiology, prevention and management of this complication with special emphasis on percutaneous intervention.     

TAP,HLA-DQB1, and HLA-DRB1 polymorphism in Colombian patients with primary Sjögren's syndrome

OBJECTIVE: Although primary Sj?gren's syndrome (pSS) has a worldwide distribution, little data is available on pSS immunogenetics in non-white populations. Thus, we investigated the influence of transporters associated with antigen processing (TAP), human leukocyte antigen (HLA)-DQB1, and HLA-DRB1 gene polymorphism in mestizo Colombian patients with pSS. METHODS: In this cross-sectional and controlled study, all patients met the European criteria for classification of pSS. TAP and HLA typing was performed by polymerase chain reaction techniques. Genetic data analysis was performed to detect deviations from the expected Hardy-Weinberg (H-W) proportions and to determine the presence of population stratification or subdivision and the existence of linkage disequilibrium between pairs of loci. RESULTS: Seventy-three Colombian patients with pSS (95% women) and 76 healthy controls were studied. Although significant associations were not observed between TAP or HLA polymorphism and disease, strong linkage disequilibrium among the loci TAP2 and DQB1 was found in patients. Deviations from the H-W expected value were found in the DQB1 locus of patients (P =.02). HLA-DRB1*0301-DQB1*0201 haplotype was associated with more severe histopathologic disease (odds ratio [OR], 15.5; 95% confidence interval [CI], 1.9-129; P =.001) and the presence of anti-Ro (OR, 3.8; 95% CI, 1-15; P =.04) and anti-La antibodies (OR, 4.3; 95% CI, 1.3-14; P =.01). CONCLUSION: The data show genetic evidence suggesting that, in Colombians, a region immersed or in the vicinity in the HLA class II system is strongly associated with a predisposition to acquire pSS, which is probably located between the TAP2 and HLA-DQB1 locus. Our results confirm that the HLA-DRB1*0301-DQB1*0201 haplotype participates in the pathogenesis of pSS.     

Asphyxia and hyaline membrane disease in neonatal monkeys

An animal model for studying the relationship between perinatal asphyxia and hyaline membrane disease (HMD) is described. The HMD developed in these Macaca mulatta (rhesus) and M. arctoides (stump tail) monkeys was clinically, physiologically, and histologically similar to that seen in human infants. The monkeys were delivered by cesarean section at a gestational age of 85-91% of term when surfactant, though present, was less than mature levels. Asphyxia at birth proved to be an important factor in disease development. Five minutes of asphyxia immediately before the first breath greatly increased the incidence and severity of HMD when compared to nonasphyxiated controls of a similar gestational age. Amniotic fluid L/S ratios did not differ significantly in the asphyxiated and control groups but data based on static pressure-volume studies of the excised lungs indicated that the surfactant activity of the asphyxiated group was significantly less. Lung maturity with regard to surfactant production appears to be a critical factor. The data from these experiments, together with data cited in the literature, strongly suggest that the lung and its surfactant system is most vulnerable to hypoxia and/or acidosis during the early stages of surfactant production. The asphyxiated non-human primate model used here should prove valuable for studying the pathogenesis of HMD and especially for further clarifying the relationship between perinatal asphyxia and HMD.