Pulsed Electromagnetic Field Protects Against Brain Injury After Intracerebral Hemorrhage: Involvement of Anti-Inflammatory Processes and Hematoma Clearance via CD36.

Intracerebral hemorrhage causes high mortality and morbidity, but its therapy methods are limited. In the present study, pulsed electromagnetic field (PEMF) was demonstrated to have beneficial effects on an intracerebral hemorrhage (ICH) model. This study explored the effects and underlying mechanisms of PEMF in a mouse model of ICH and cultured BV2 cells. PEMF was applied 4 hours after collagenase-induced ICH at day 0 and 4 hours per day for seven consecutive days. The expression levels of proinflammatory factors were assessed by ELISA kits and western blotting. Hematoma volume was measured by histological analysis. The effects of PEMF on phagocytosis of the erythrocytes were observed in cultured BV2 cells and ICH mouse models. Seven days after ICH, the hematoma volume was significantly reduced in PEMF-treated animals compared to nontreated mice. We found that PEMF decreased the hematoma volume and the expression levels of proinflammatory factors after ICH. Moreover, PEMF enhanced the erythrophagocytosis of microglia via CD36. Furthermore, we found that downregulation CD36 with Genistein blocked the effects of PEMF-induced hematoma clearance and anti-inflammations effects. Thus, the PEMF-mediated promotion of neurological functions may at least partly involve anti-inflammatory processes and hematoma clearance. These results suggest that PEMF treatment promoted the hematoma clearance and alleviated the inflammation after ICH.

SR-BI as target in atherosclerosis and cardiovascular disease - A comprehensive appraisal of the cellular functions of SR-BI in physiology and disease.

High-density lipoprotein (HDL) is considered an anti-atherogenic lipoprotein species due to its role in reverse cholesterol transport. HDL delivers cholesterol esters to the liver through selective uptake by scavenger receptor class B type I (SR-BI). In line with the protective role for HDL in the context of cardiovascular disease, studies in mice and recently also in humans have shown that a disruption of normal SR-BI function predisposes subjects to the development of atherosclerotic lesions and cardiovascular disease. Although SR-BI function has been studied primarily in the liver, it should be acknowledged that the SR-BI protein is expressed in multiple tissues and cell types across the body, albeit at varying levels between the different tissues. Given that SR-BI is widely expressed throughout the body, multiple cell types and tissues can theoretically contribute to the atheroprotective effect of SR-BI. In this review the different functions of SR-BI in normal physiology are highlighted and the (potential) consequences of cell type-specific disruption of SR-BI function for atherosclerosis and cardiovascular disease susceptibility discussed. It appears that hepatocyte and platelet SR-BI inhibit respectively the development of atherosclerotic lesions and thrombosis, suggesting that SR-BI located on these cell compartments should be regarded as being a protective factor in the context of cardiovascular disease. The relative contribution of SR-BI present on endothelial cells, steroidogenic cells, adipocytes and macrophages to the pathogenesis of atherosclerosis and cardiovascular disease remains less clear, although proper SR-BI function in these cells does appear to influence multiple processes that impact on cardiovascular disease susceptibility.

Platelet and soluble glycoprotein VI - novel applications in diagnosis and therapy.

One of the key receptors involved in the prothrombotic stage of an acute coronary syndrome (ACS) is platelet glycoprotein VI (GPVI). This constitutively expressed collagen receptor is platelet-specific and has shown to be a useful biomarker tool for the early detection of atheroslerotic diseases such as ACS and ischemic stroke. In a multimarker panel of several biomarkers, platelet GPVI may contribute to risk stratification and prediction of clinical outcome in patients with symptomatic atherosclerotic diseases. Moreover, the soluble receptor of GPVI may also be an interesting and prospective target for molecular imaging to identify sites of vulnerable plaques as the results of preclinical studies suggest. Apart from the diagnostic use of platelet as well as soluble, plasmatic GPVI, therapeutical implications may be the blockade of collagen binding sides of GPVI, as platelet GPVI is not able to bind to collagen where the binding sides were already saturated with soluble GPVI. This therapeutic aspect could serve as a promising strategy for antithrombotic and antiatherosclerotic therapy in future.

A CD36 synthetic peptide inhibits silica-induced lung fibrosis in the mice.

Silicosis is a kind of pneumoconiosis caused by inhalation of silica dust, which is characterized by lung fibrosis. The biologically active form of transforming growth factor-beta1 (TGF-beta1) plays a key role in the development of lung fibrosis. CD36 is involved in the transformation of latent TGF-beta1 (L-TGF-beta1) to active TGF-beta1. The antagonistic effect of the synthetic peptide was analyzed by the administration of CD36 (93-110) synthetic peptide to the silicosis model of mice. The hydroxyproline content of the silica + CD36 (93-110) synthetic peptide group was significantly lower than that of the other experimental groups [silica and silica + CD36 (208-225) synthetic peptide groups] (p < .05). Inflammation, fibrotic degree and distribution of collagen fibers in silicotic nodules of the silica + CD36 (93-110) synthetic peptide group were less than those of the other experimental groups. The expressions of collagen I and III of the silica + CD36 (93-110) synthetic peptide group were significantly lower than those of the other experimental groups (p < .05). CD36 (93-110) synthetic peptide reduced the tissue fibrotic pathologies and collagen accumulation in the silicosis model of mice, resulting in the decreased severity of silica-induced lung fibrosis.

Platelets activated by collagen through the immunoreceptor tyrosine-based activation motif in the Fc receptor gamma-chain play a pivotal role in the development of myocardial ischemia-reperfusion injury.

Platelet activation and the formation of platelet microaggregates in coronary vessels play pivotal roles in myocardial ischemia and reperfusion injury. The Fc receptor gamma-chain (FcR gamma) is coexpressed with glycoprotein (GP) VI, forming a platelet collagen receptor, and the activation of platelets by collagen is closely coupled with tyrosine phosphorylation of the FcRgamma. To examine the functional significance of platelet FcR gamma/GPVI complex in the early phase of myocardial ischemia and reperfusion injury in mice, we performed coronary occlusion and reperfusion experiments using wild type mice and FcRgamma-deficient (FcRgamma(-/-)) mice that lack GPVI. The infarct size was significantly smaller in FcRgamma(-/-) mice subjected to occlusion and reperfusion of the coronary artery than in control FcR gamma(+/+) mice. Twenty-four hours after the reperfusion, electron microscopy of the injured tissue showed substantially more platelet aggregation and occlusive platelet microthrombi in the capillaries of the damaged areas of the wild type mice than in those of the FcR gamma(-/-) mice. Platelet Syk was scarcely activated in the FcR gamma(-/-) mice after myocardial ischemia and reperfusion, but significantly activated in the FcR gamma(+/+) mice. CD11b expression on neutrophils was elevated after myocardial ischemia and reperfusion in both mouse groups, whereas myeloperoxidase activity in the injured areas was significantly lower in the FcRgamma(-/-) mice than in the FcRgamma(+/+) mice. These results suggest that the collagen-induced activation of platelets through the FcR gamma plays a pivotal role in the extension of myocardial ischemia-reperfusion injury. FcRgamma and GPVI may be important therapeutic targets for myocardial ischemia-reperfusion injury.