The present study investigates the regulation of small ubiquitin-related modifier-1 (SUMO-1) expression in response to hypoxia in adult mouse brain and heart. We observed a significant increase in SUMO-1 mRNAs and proteins after hypoxic stimulation in vivo. Because SUMO-1 interacts with various transcription factors, including hypoxia-inducible factor1b (HIF-1b) in vitro, we not only demonstrated that the HIF-1a expression is increased by hypoxia in brain and heart, but also provided evidence that SUMO-1 co-localizes in vivo with HIF1a in response to hypoxia by demonstrating the co-expression of these two proteins in neurons and cardiomyocytes. The specific interaction between SUMO-1 and HIF-1a was additionally demonstrated with co-immunoprecipitation. These results indicate that the increased levels of SUMO-1 participate in the modulation of HIF-1a function through sumoylation in brain and heart.

Abstract-Impaired fibrinolysis has been linked to atherosclerosis in a number of experimental and clinical studies.Plasminogen activator inhibitor type 1 (PAI-1) is the primary inhibitor of plasminogen activation and has been proposed to promote atherosclerosis by facilitating fibrin deposition within developing lesions. We examined the contribution of PAI-1 to disease progression in 2 established mouse models of atherosclerosis. Mice lacking apolipoprotein E (apoEϪ/Ϫ) and mice lacking the low density lipoprotein receptor (LDLRϪ/Ϫ) were crossbred with transgenic mice overexpressing PAI-1 (resulting in PAI-1 Tg ϩ /apoEϪ/Ϫ and PAI-1 Tg ϩ /LDLRϪ/Ϫ, respectively) or were crossbred with mice completely deficient in PAI-1 gene expression (resulting in PAI-1Ϫ/Ϫ/apoEϪ/Ϫ and PAI-1Ϫ/Ϫ/LDLRϪ/Ϫ, respectively). All animals were placed on a western diet (21% fat and 0.15% cholesterol) at 4 weeks of age and analyzed for the extent of atherosclerosis after an additional 6, 15, or 30 weeks. Intimal and medial areas were determined by computer-assisted morphometric analysis of standardized microscopic sections from the base of the aorta. Atherosclerotic lesions were also characterized by histochemical analyses with the use of markers for smooth muscle cells, macrophages, and fibrin deposition. Typical atherosclerotic lesions were observed in all experimental animals, with greater severity at the later time points and generally more extensive lesions in apoEϪ/Ϫ than in comparable LDLRϪ/Ϫ mice. No significant differences in lesion size or histological appearance were observed among PAI-1Ϫ/Ϫ, PAI-1 Tg ϩ , or PAI-1 wild-type mice at any of the time points on either the apoEϪ/Ϫ or LDLRϪ/Ϫ genetic background. We conclude that genetic modification of PAI-1 expression does not significantly alter the progression of atherosclerosis in either of these well-established mouse models. These results suggest that fibrinolytic balance (as well as the potential contribution of PAI-1 to the regulation of cell migration) plays only a limited role in the pathogenesis of the simple atherosclerotic lesions observed in the mouse. Key Words: atherosclerosis Ⅲ plasminogen activator inhibitor-1 Ⅲ apolipoprotein E Ⅲ low density lipoprotein receptors Ⅲ transgenic mice

BackgroundCardiovascular disease is the most common cause of death for both genders. Debates are ongoing as to whether gender-specific differences in clinical course, diagnosis, and management of acute myocardial infarction (MI) exist.Methods and ResultsWe compared all men and women who were treated for acute MI at cardiac care units in Västra Götaland, Sweden, between January 1995 and October 2014 by obtaining data from the prospective SWEDEHEART (Swedish Web-System for Enhancement of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry. We performed unadjusted and adjusted Cox proportional hazards and logistic regression analyses on complete case data and on imputed data sets. Overall, 48 118 patients (35.4% women) were diagnosed with acute MI. Women as a group had better age-adjusted prognosis than men, but this survival benefit was absent for younger women (aged <60 years) and for women with ST-segment elevation MI. Compared with men, younger women and women with ST-segment elevation MI were more likely to develop prehospital cardiogenic shock (adjusted odds ratio 1.67, 95% CI 1.30 to 2.16, P<0.001 and adjusted odds ratio 1.31, 95% CI 1.16 to 1.48, P<0.001) and were less likely to be prescribed evidence-based treatment at discharge (P<0.001 for β-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, statins, and P2Y12 antagonists). Differences in treatment between the genders did not decrease over the study period (P>0.1 for all treatments).ConclusionsWomen on average have better adjusted prognosis than men after acute MI; however, younger women and women with ST-segment elevation MI have disproportionately poor prognosis and are less likely to be prescribed evidence-based treatment.

Among the 38 statements in NHP as a judgment of QL prior to CABG, one of them, "I feel lonely" was independently associated with survival both at 30 days and 5 years after CABG.

Objective-To identify determinants of an inferior quality of life (QoL) five years after coronary artery bypass grafting (CABG). Setting-University hospital.