Establishment of Nasal Tolerance to Heat Shock Protein-60 Alleviates Atherosclerosis by Inducing TGF-β-dependent Regulatory T Cells / 华中科技大学学报（医学）（英德文版）

Mounting evidence supports that a newly identified regulatory T cell (Treg),CD4+LAP+ Treg,is associated with oral tolerance induction and following inhibition of atherosclerosis,but little is described about whether nasal tolerance to antigen likewise induces the novel Tregs production and the relevant antiatherosclerotic benefit.We investigated the effect of nasal administration of heat shock protein-60 (HSP60) on atherogenesis.HSP60 or phosphate buffer solution (PBS) was nasally adminis-tered to six-week-old male ApoE (-/-) mice.At the 10th week after the nasal administration,there was a significant decrease in atherosclerotic plaque areas of aortic roots in the HSP60-treated mice as compared with those in the PBS-treated mice.Atherosclerosis suppression was accompanied with a significant increase in CD4+LAP+ and CD4+CD25+Foxp3+ Tregs and a concurrently increased production of TGF-β in the HSP60-treated mice.The protective effect of HSP60 was offset by injection of anti-TGF-β antibody.It is concluded that nasal administration of HSP60 can inhibit atherosclerotic formation through immune tolerance which is established by Tregs depending on the induction of anti-inflammatory cytokine TGF-β.Immune tolerance induced by nasal administration of HSP60 may provide an alternative therapeutic method for atherosclerosis.

PDGF-induced Proliferation of Smooth Muscular Cells Is Related to the Regulation of CREB Phosphorylation and Nur77 Expression / 华中科技大学学报（医学）（英德文版）

This study examined the relationship between PDGF-induced proliferation of vascular smooth muscle cells (VSMCs) and Nur77 expression and the effect of atorvastatin on VSMC proliferation and Nur77 in PDGF-treated VSMCs.Rat VSMCs were isolated and cultured.After incubation with atorvastatin or Nur77 siRNA,the cells were stimulated with PDGF and detected for BrdU incorporation to measure the proliferation of the VSMCs.Quantitative PCR and Western blotting were used to determine the Nur77 protein and the CREB phosphorylation level,to observe their relations with PDGF-induced VSMC proliferation.Our results showed that PDGF increased the BrdU incorporation in VSMCs,suggesting that it induced the proliferation of the cells.The VSMC proliferation was associated with increased Nur77 expression and elevated CREB phosphorylation.Atorvastatin inhibited the PDGF-induced VSMC proliferation,suppressed Nur77 expression.After silencing of Nur77 gene,the PDGF-induced VSMC proliferation was decreased.It was concluded that PDGF-induced VSMC proliferation was related to the Nur77 expression and CREB phosphorylation.Atorvastatin reduced the Nur77 expression and,at the same time,inhibited the VSMC proliferation.

Expression and Significance of fgl2 Prothrombinase in Cardiac Microvascular Endothelial Cells of Rats with Type 2 Diabetes / 华中科技大学学报（医学）（英德文版）

Microthrombosis may be involved in the pathogenesis of cardiac microangiopathy due to diabetes. Recent studies have shown that fibrinogen-like protein 2 (fgl2) plays a pivotal role in microthrombosis in viral hepatitis, acute vascular xenograft rejection and cytokine-induced fetal loss syndrome. The current study was designed to examine the expression of fgl2 in microvascular endothelial cells and investigate the effects of microthrombi due to fgl2 on cardiac function and structure in rats with type 2 diabetes. Following induction of type 2 diabetes, 24 rats were observed dynamically. Fgl2 expression and related cardiac microthrombosis were examined. Local or circulating TNF-a was measured. Coronary flow (CF) per min was calculated as an index of cardiac microcirculation. Cardiac function and morphology were evaluated. It was found that Fgl2 was highly expressed in cardiac microvascular endothelial cells of rats with type 2 diabetes, which was promoted by local or circulating TNF-α. The Fgl2 expression was associated with cardiac hyaline microthrombosis. In parallel with the fgl2 expression, CF per min, cardiac diastolic or systolic function and cardiac morphology were aggravated to some extent. It was concluded that in rats with type 2 diabetes, microthrombosis due to fgl2 contributes to the impairment of cardiac diastolic or systolic function and morphological changes.

Increased Expression and Activity of MMP-9 in C-reactive Protein- induced Human THP-1 Mononuclear Cells Is Related to Activation of Nuclear Factor Kappa-B / 华中科技大学学报（医学）（英德文版）

n of NF-κ3. Down-regulation of the expression and activity of MMP-9 may be a new treatment alternative for plaque stabilization by inhibiting the NF-κB activation.