Carbon Monoxide Releasing Molecule Accelerates Reendothelialization after Carotid Artery Balloon Injury in Rat

Objective This study was aimed to investigate the effects of carbon monoxide releasing molecule （CORM-2）, a novel carbon monoxide carrier, on the reendothelialization of carotid artery in rat endothelial denudation model. Methods Male rats subjected to carotid artery balloon injury were treated with CORM-2, inactive CORM-2 （iCORM-2） or dimethyl sulfoxide （DMSO）. The reendothelialization capacity was evaluated by Evans Blue dye and the immunostaining with anti-CD31 antibody. The number of circulating endothelial progenitor cells （EPCs） was detected by flow cytometry. The proliferation, migration, and adhesion of human umbilical vein endothelial cells （HUVECs） were assessed by using [3H]thymidine, Boyden chamber and human fibronectin respectively. The expressions of protein were detected by using western blot analysis. Results CORM-2 remarkably accelerated the re-endothelialization 5 d later and inhibited neointima formation 28 d later. In addition, the number of peripheral EPCs significantly increased in CORM-2-treated rats than that in iCORM-2 or DMSO-treated rats after 5 d later. In vitro experiments, CORM-2 significantly enhanced the proliferation, migration and adhesion of HUVECs. The levels of Akt, eNOS phosphorylation, and NO generation in HUVECs were also much higher in CORM-2 treated group. Blocking of PI3K/Akt/eNOS signaling pathway markedly suppressed the enhanced migration and adhesion of HUVECs induced by CORM-2. Conclusion CORM-2 could promote endothelial repair, and inhibit neointima formation after carotid artery balloon injury, which might be associated with the function changes of HUVECs regulated by PI3K/Akt/eNOS pathway.

A multi-functional MgF_(2)/polydopamine/hyaluronan-astaxanthin coating on the biodegradable ZE21B alloy with better corrosion resistance and biocompatibility for cardiovascular application

The cardiovascular diseases(CVD)continue to be the major threat to global public health over the years,while one of the effective methods to treat CVD is stent intervention.Biomedical magnesium(Mg)alloys have great potential applications in cardiovascular stents benefit from their excellent biodegradability and absorbability.However,excessive degradation rate and the delayed surface endothelialization still limit their further application.In this study,we modified a Mg-Zn-Y-Nd alloy(ZE21B)by preparing MgF_(2) as the corrosion resistance layer,the dopamine polymer film(PDA)as the bonding layer,and hyaluronic acid(HA)loaded astaxanthin(ASTA)as an important layer to directing the cardiovascular cells fate.The electrochemical test results showed that the MgF_(2)/PDA/HA-ASTA coating improved the corrosion resistance of ZE21B.The cytocompatibility experiments also demonstrated that this novel composite coating also selectively promoted endothelial cells proliferation,inhibited hyperproliferation of smooth muscle cells and adhesion of macrophages.Compared with the HAloaded rapamycin(RAPA)coating,our MgF_(2)/PDA/HA-ASTA coating showed better blood compatibility and cytocompatibility,indicating stronger multi-functions for the ZE21B alloy on cardiovascular application.

Immobilization of heparin on decellularized kidney scaffold to construct microenvironment for antithrombosis and inducing reendothelialization

In recent years, rapid development of tissue engineering technology provides possibilities for the construction of artificial tissues or organs. In construction of engineered kidneys, researchers used native decellularized extracellular matrix(ECM) as the scaffolds to recellularization. However, thrombosis has been a great issue that hinders the progress of transplantation in vivo. In this study, heparin was immobilized to the collagen part of decellularized scaffold with collagen-binding peptide(CBP). Through the anticoagulant and endothelial cell reperfusion experiments, it can be demonstrated that the heparinized scaffolds absorbed less platelets and red blood cells which can effectively reduce the formation of thrombosis. Moreover, it is conducive to longterm adhesion of endothelial cells which is important for the formation of subsequent vascularization. Taken together, our results reveal that the whole kidney can be modified by CBP-heparin composite to reduce the thrombosis and provide the better conditions for neovascularization.

Berberine-Promoted CXCR4 Expression Accelerates Endothelial Repair Capacity of Early Endothelial Progenitor Cells in Persons with Prehypertension

Objective： To evaluate whether the berberine treatment can improve endothelial repair capacity of early endothelial progenitor cells （EPCs） from prehypertensive subjects through increasing CXC chemokine receptor 4 （CXCR4） signaling. Methods： EPCs were isolated from prehypertensive and healthy subjects and cultured. In vivo reendothelialization capacity of EPCs from prehypertensive patients with or without in vitro berberine treatment was examined in a nude mouse model of carotid artery injury. The protein expressions of CXCR4/Janus kinase-2 （JAK-2） signaling of in vitro EPCs were detected by Western blot analysis. Results： CXCR4 signaling and alteration in migration and adhesion functions of EPCs were evaluated. Basal CXCR4 expression was significantly reduced in EPCs from prehypertensive patients compared with normal subjects （P〈0.01）. Also, the phosphorylation of JAK-2 of EPCs, a CXCR4 downstream signaling, was significantly decreased （P〈0.01）. Berberine promoted CXCR4/JAK-2 signaling expression of in vitro EPCs （P〈0.01）. Transplantation of EPCs pretreated with berberine markedly accelerated in vivo reendothelialization （P〈0.01）. The increased in vitro function and in vivo reendothelialization capacity of EPCs were inhibited by CXCR4 neutralizing antibody or pretreatment with JAK-2 inhibitor AG490, respectively （P〈0.01）. Conclusion： Berberine- modified EPCs via up-regulation of CXCR4 signaling contributes to enhanced endothelial repair capacity in prehypertension, indicating that berberine may be used as a novel potential primary prevention means against prehypertension-related atherosclerotic cardiovascular disease.

The role of endothelial progenitor cells in restenosis and stent thrombosis after percutaneous coronary intervention

Background After percutaneous coronary intervention （PCI）, some patients may suffer from restenosis and stent thrombosis. Many studies suggest that endothelial progenitor cell （EPC） has an important role in preventing restenosis and stent thrombosis. A novel stent which can attract EPC has been designed to provide a better outcome for these problems. Method The data of the present review was obtained by searching PUBMED and other databases （ 1994-2011 ） using the key terms of ＂endothelial progenitor cell＂, ＂reendothelialization＂, ＂restenosis＂, ＂stent thrombosis＂, and ＂percntaneous coronary intervention＂. Result Rapid reendothelialization is essential in preventing restenosis and stent thrombosis. EPC can differentiate into endothelial cell and accelerate the reendothelialization. After numerous preclinical and clinical researches, the correlation between circulating EPCs to restenosis still remains poorly understood. However, many studies have shown the important role of EPC in diminishing the risk of thrombosis following stent implantation. Some pharmacological agents have been reported can increase the number and/or functions of EPC. Recently, CD34＋ antibody coated stent has been developed to attract EPC to the healing endothelium, and has showed favorable results. Conclusion EPC has important role in rapid reendothelialization after vascular injury. EPC can prevent stent thrombosis after PCI, however the effects of EPC in preventing restenosis need further investigations. The capturing CD34＋ stent is safe and significantly decreases stent thrombosis.