Cardioprotection by adiponectin

Obesity-related disorders are closely associated with the pathogenesis of cardiovascular disease. Adiponectin is a circulating adipose tissue-derived hormone that is down-regulated in obese individuals. Hypoadiponectinemia has been identified as an independent risk factor for type 2 diabetes, coronary artery disease, and hypertension, and experimental studies show that adiponectin plays a protective role in the development of insulin resistance, atherosclerosis, and inflammation. More recent findings have shown that adiponectin directly affects signaling in myocardial cells and exerts beneficial actions on the heart after pressure overload and ischemia-reperfusion injury. This review focuses on the role of adiponectin in the regulation of myocardial remodeling and acute cardiac injury.     

Cholestasis protects the liver from ischaemic injury and post-ischaemic inflammation in the mouse

BACKGROUND AND HYPOTHESIS: Cholestasis is associated with high morbidity and mortality in patients undergoing major liver surgery, but the mechanisms responsible remain elusive. Increased ischaemic liver injury and inflammation may contribute to the poor outcome. METHODS: Common bile duct ligation (biliary obstruction with hyperbilirubinaemia) or selective ligation of the left hepatic duct (biliary obstruction without hyperbilirubinaemia) was performed in C57BL/6 mice before 1 h of hepatic ischaemia and 1, 4 or 24 h of reperfusion. Infection with the intracellular hepatic pathogen Listeria monocytogenes for 12 and 48 h was used to study ischaemia-independent hepatic inflammation. RESULTS: Cholestatic mice showed considerable protection from ischaemic liver injury as determined by transaminase release, histological liver injury and neutrophil infiltration. In cholestatic mice, reduced injury correlated with a failure to activate nuclear factor kappaB (NFkappaB) and tumour necrosis factor alpha (TNFalpha) mRNA synthesis, two key mediators of post-ischaemic liver inflammation. After selective bile duct ligation, both the ligated and the non-ligated lobes showed blocked activation of NFkappaB as well as reduced induction of TNFalpha mRNA synthesis and neutrophil infiltration. By contrast, infection with L monocytogenes showed comparable activation of NFkappaB and hepatic recruitment of neutrophils 12 h after infection. CONCLUSION: Cholestasis does not increase but rather dramatically protects the liver from ischaemic injury and inflammation. This effect is mediated by a systemic factor, but not bilirubin, and is associated with a preserved capacity to trigger an inflammatory response to other stimuli such as a bacterial pathogen.     

Intracellular survival pathways in the liver.

Recent studies have drawn attention to cytokines as important modulators of hepatocyte cell death during acute and chronic liver disease. Through interaction with cell surface receptors, they activate specific intracellular pathways that influence cell fate in different manners. For example, tumor necrosis factor not only induces proapoptotic signals via the caspase cascade but also activates intracellular survival pathways, namely the nuclear factor (NF)-kappaB pathway. In this article, we will focus on the function of the NF-kappaB pathway in liver physiology and pathology. Especially, recent data based on experiments with genetically modified mice will be discussed, which demonstrated important and controversial functions of this pathway e.g. in cytokine-mediated hepatocyte apoptosis, ischemia-reperfusion injury, liver regeneration and the development of hepatocellular carcinoma. Moreover, the role of the interleukin-6 pathway and its possible protective function in the context of liver failure will be summarized.     

泛素-蛋白酶体通路在心血管疾病中作用的研究进展

泛素蛋白酶体通路(UPS)除了介导细胞内蛋白质的降解外,还在细胞周期、基因转录及表达、信号转导、凋亡、抗原提呈和炎症等方面发挥重要的作用。近年来的研究发现,该通路还在心肌病、心力衰竭、缺血再灌注损伤、动脉粥样硬化、血管的再狭窄等心血管疾病方面,起着重要的病理生理作用。本文就近期UPS在心血管疾病方面的进展进行综述如下。