Search

Background: Both morbidity and mortality of hypertension are high. Whether pneumonia and lung cancer affect the mortality of men with hypertension is not well studied. The aim of the study was to study the association between pneumonia/lung cancer and the mortality among male individuals with hypertension. Methods: A cross-sectional study was performed on hypertensive men, who admitted into our hospital and lived in eligible downtown areas prior to admission. Variety statistical analyses were performed, including logistic regression to assess the association between pneumonia/lung cancer and the mortality. Results: 14354 patients were enrolled. Mean age of them was 68.9±12.4 year old (y) and dead ones was 75.9±9.5y. The hospitalized mortality was 5.9%, which was increased with age: the mortality of group ≦49y, 50-59y, 60-69y, 70-79y, 80-89y and ≧90y was 0.7%, 2.2%, 2.9%, 7.1%, 11.1% and 16.6% respectively. The increased mortality was significantly positively correlated with the prevalence of pneumonia in different age, P Conclusions: The study provides evidence that pneumonia and lung cancer significantly affect mortality of hypertensive men in downtown areas, bringing alert that in order to reduce the mortality of hypertension in mordent life, theses lung diseases should be prevented and treated intensively. Key Words: hypertension, hospitalized mortality, pneumonia, lung cancer

Background— Leptin is an adipocyte-derived hormone critical for energy homeostasis and implicated in vascular disease processes. The relevant cellular leptin receptor pools and signaling pathways involved in leptin-related vascular phenotypes in vivo are unclear. Methods and Results— Arterial injury was induced in wild-type ( wt ), leptin-deficient ( lep ob/ob ), and leptin receptor–deficient ( lepr db/db ) mice. Compared with wt mice, lep ob/ob and lepr db/db mice were protected from the development of neointima. Bone marrow transplantation experiments between wt and lepr db/db mice indicated that the vascular protection in lepr db/db mice was not attributable to lack of leptin receptor expression on bone marrow–derived elements. To investigate the role of the lepr- mediated signal transducer and activator of transcription 3 (STAT3) signaling pathway in the response to vascular injury, lepr s/s mice homozygous for a leptin receptor defective in STAT3 signaling underwent femoral arterial injury. Despite similar obesity and blood pressure levels, the neointimal area in lepr s/s mice was significantly increased compared with lepr db/db mice. Conclusions— The molecular mechanism by which the leptin receptor mediates neointima formation and vascular smooth muscle cell proliferation is largely independent of the STAT3-dependent signaling pathways involved in energy balance.

Fabry disease is an X-linked lysosomal storage disorder due to deficiency of α-galactosidase A (GLA) activity that results in the widespread accumulation of neutral glycosphingolipids. Renal failure, neuropathy, premature myocardial infarction, and stroke occur in patients with this condition primarily due to deposition of glycosphingolipids in vascular endothelial cells. The clinical consequences of Fabry disease suggest that vascular thrombosis may play a prominent role in the pathogenesis of this disease; however, the vasculopathy associated with Fabry disease has not been extensively studied. To determine if mice genetically deficient in Gla are susceptible to vascular thrombosis, a photochemical carotid injury model was used to induce occlusive thrombosis. In this model, Gla − /0 mice displayed a progressive age-dependent shortening of the time to occlusive thrombosis after vascular injury that correlated with progressive accumulation of globotriasylceramide (Gb3) in the arterial wall. Bone marrow transplantation from Gla − /0 to Gla+/0 mice and from Gla+/0 to Gla − /0 mice did not change the thrombotic phenotype of the host. These studies reveal a potent vascular prothrombotic phenotype in Gla -deficient mice and suggest that antithrombotic therapies as well as therapies designed to reduce the vascular accumulation of Gb3 may have beneficial effects on thrombotic complications in patients with Fabry disease. E-mail: deitzman@umich.edu

Background— Factor V Leiden (FVL) is a common genetic risk factor for vascular thrombosis in humans. Fabry disease, an X-linked lysosomal storage disorder attributable to α-galactosidase A (GLA) deficiency, is associated with premature vascular events that may be thrombotic in nature. Methods and Results— To examine a potential interaction between FvL and Gla deficiency in vivo, we analyzed tissue fibrin deposition in mice carrying combined mutations in FvL and Gla . Gla deficiency markedly increased tissue fibrin deposition in mice carrying the FvL mutation (0.33±0.03%; n=7) compared with FvL mutation (0.14±0.02%; n=10; P Conclusions— These observations demonstrate a synergistic interaction between Gla deficiency and FvL toward tissue fibrin deposition in mice. Concomitant mutations in these genes may increase the penetrance of vascular thrombotic events in humans.

Leptin is an adipocyte-derived hormone that has been shown to exert both beneficial metabolic effects and potentially adverse vascular effects in preclinical studies. To determine the effects of leptin receptor signaling pathways on atherosclerosis in the setting of obesity and hyperlipidemia, mice were generated with deficiency of apolipoprotein E ( ApoE −/− ) and either wild-type leptin receptor expression ( Lepr +/+ ,ApoE −/− ), mutant leptin receptor expression defective in all leptin receptor signaling pathways ( Lepr db/db ,ApoE −/− ), or mutant leptin receptor with selective deficiency of leptin receptor-STAT3 signaling ( Lepr s/s ,ApoE −/− ). At 27 weeks of age, which included 7 weeks on western chow, Lepr db/db ,ApoE −/− developed increased weight (61.9 ±3.5 vs 28±2.5, pLepr +/+ ,ApoE −/− mice. In contrast, despite similar obesity and hyperlipidemia to Lepr db/db ,ApoE −/− mice, the atherosclerosis in Lepr s/s ,ApoE −/− was less than Lepr db/db ,ApoE −/− mice (7.3±1 vs 13.9±1.7, p=0.003) and not significantly greater than Lepr +/+ ,ApoE −/− mice (7.3±1 vs 4.3±0.9, p=0.06 ). Hepatic steatosis and adipose inflammation were also reduced in Lepr s/s ,ApoE −/− mice compared to Lepr db/db ,ApoE −/− mice. In a mouse model of obesity and hyperlipidemia, leptin receptor signaling confers protection against hepatic steatosis, fat inflammation, and atherosclerosis. These effects are independent of leptin effects on energy balance. This research has received full or partial funding support from the American Heart Association, AHA Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota & Wisconsin).