Objective To observe the protective effect and mechanism of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG) on atherosclerosis in ApoE konck-out mice. Methods A total of 24 ApoE knock-out mice were randomly divided into normal control group (n=8), model control group (HFD, high-fat diet, n=8) and treated group (THSG, 20 mg·kg-1, i.g., n=8). The atherosclerosic plaque of aorta wall and aorta root were measured by oil red O staining; The expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in human umbilical vein endothelial cells (HUVEC) through C-reaction protein (CRP) was studied by Western blotting.Results The atherosclerosis plaque in normal control group was not observed. The lipid accumulation decreased in the aorta and the plaque areas in the aortic sinus in THSG treated-group compared with model control group. Moreover, THSG down-regulated CRP-induced LOX-1 expression in HUVEC. Conclusion The atheroscletosis plaque in ApoE knock-out mice was decreased by THSG. The mechanism might be related to the inhibition of the expression of LOX-1 protein.
CHEN XP, ZHANG TT, DU GH.Lectin-like oxidized low-density lipoprotein receptor-1, a new promising target for the therapy of atherosclerosis[J]. Cardiovas Drug Rev, 2007, 25(2):146-161.
BURNETT MS, GAYDOS CA, MADICO GE, et al.Atheroscletosis in apoE knockout mice infected with multiple pathogens[J]. J Infect Dis, 2001, 183(2): 226-231.
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WEYMANNA, SCHMACKB, OKADAT, et al.Reendothelialization of human heart valve neoscaffolds using umbilical cord-derived endothelial cells[J]. Circ J, 2013, 77(2): 207-216.
Abstract BACKGROUND: Heart valve tissue engineering represents a concept for improving the current methods of valvular heart disease therapy. The aim of this study was to develop tissue engineered heart valves combining human umbilical vein endothelial cells (HUVECs) and decellularized human heart valve matrices. METHODS AND RESULTS: Pulmonary (n=9) and aortic (n=6) human allografts were harvested from explanted hearts from heart transplant recipients and were decellularized using a detergent-based cell extraction method. Analysis of decellularization success was performed with light microscopy, transmission electron microscopy and quantitative analysis of collagen and elastin content. The decellularization method resulted in full removal of native cells while the mechanical stability and the quantitative composition of the neoscaffolds was maintained. The luminal surface of the human matrix could be successfully recellularized with in vitro expanded HUVECs under dynamic flow conditions. The surface appeared as a confluent cell monolayer of positively labeled cells for von Willebrand factor and CD 31, indicating their endothelial nature. CONCLUSIONS: Human heart valves can be decellularized by the described method. Recellularization of the human matrix resulted in the formation of a confluent HUVEC monolayer. The in vitro construction of tissue-engineered heart valves based on decellularized human matrices followed by endothelialization using HUVECs is a feasible and safe method, leading to the development of future clinical strategies in the treatment of heart valve disease.
HEIN TW, QAMIRANIE, RENY, et al.Selective activation of lectin-like oxidized low-density lipoprotein receptor-1 mediates C-reactive protein-evoked endothelial vasodilator dysfunction in coronary arterioles[J]. Circ Res, 2014,114(1): 92-100.
Studies in cultured endothelium implicate that lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) or Fc纬 receptor II (CD32) contributes to the proatherogenic effects of C-reactive protein (CRP). However, the identity of the receptors linking to deleterious actions of CRP in vasomotor regulation remains unknown.We tested the hypothesis that LOX-1 contributes to adverse effects of CRP on endothelium-dependent vasomotor function in resistance arterioles.Porcine coronary arterioles were isolated for vasoreactivity study, dihydroethidium fluorescence staining of superoxide, immunohistochemical localization of receptors, immunoprecipitation of receptor/CRP interaction, and protein blot. Intraluminal treatment of pressurized arterioles with a pathophysiological level of CRP (7 碌g/mL; 60 minutes) attenuated endothelium-dependent nitric oxide-mediated and prostacyclin-mediated dilations to serotonin and arachidonic acid, respectively. LOX-1 and CD32 were detected in the endothelium of arterioles. Blockade of LOX-1 with either pharmacological antagonist 魏-carrageenan or anti-LOX-1 antibody prevented the detrimental effect of CRP on vasodilator function, whereas anti-CD32 antibody treatment was ineffective. Denudation of endothelium and blockade of LOX-1 but not CD32 prevented CRP-induced elevation of superoxide in the vessel wall. CRP was coimmunoprecipitated with LOX-1 and CD32 from CRP-treated arterioles. Similarly, LOX-1 and CD32 blockade prevented CRP-induced arteriolar expression of plasminogen activator inhibitor-1, a thrombogenic protein.CRP elicits endothelium-dependent oxidative stress and compromises nitric oxide-mediated and prostacyclin-mediated vasomotor function via LOX-1 activation. In contrast, both LOX-1 and CD32 mediate plasminogen activator inhibitor-1 upregulation in arterioles by CRP. Thus, activation of LOX-1 and CD32 may contribute to vasomotor dysfunction and proatherogenic actions of CRP, respectively.
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