Molecular regulation of vascular stem cell function in ischemic heart failure

A balance between growth and apoptosis plays a critical role in maintaining the homeostasis of cardiovascular tissues.During the development of atherosclerosis and atherosclerosis-associated coronary heart disease many environmental factors exert regulatory effects on cardiovascular cells and their progenitors.We have recently investigated several proteins known to protect cells against ischemic damages.Here I would like to briefly review the literature and discuss with you some of our recent findings.Clusterin(CST) or named apolipoprotein-J is a stress-responding protein with multiple biological functions,including the inhibition of apoptosis and inflammation and transport of lipids.It may also participate in cell traffic and aggregation.In the process of post-infarct cardiac tissue repair,stem cells migrate into the damaged myocardium under the influence of chemoattractive substances such as stromal cell-derived factor(SDF).We tested whether CST enhances expression of stem cell homing receptor and migration of cardiac progenitor cells (CPCs).CPCs isolated from canine hearts transduced by CST cDNA expressed high levels of CXCR4,a receptor for SDF-1.The transfected cells also showed an increased migratory response to SDF-1 stimulation. The SDF-1-mediated migration of the CST-expressing CPCs was attenuated by PI3 kinase inhibitor LY294002,but not by mitogen-activated protein /ERK kinase inhibitor PD98059.Analysis of cell cycle by flow cytometry revealed no significant difference in cell cycle between the transduced and control CPCs.Thus,CST expression may increase CPCs migration via increasing CXCR4 expression and SDF-1/chemokine receptor signaling in a PI3/ Akt-dependent manner.The growth factor,erythropoietin (Epo),ameliorates the inflammatory response of the myocardium to ischemic injury.Cardiac stem cells are vulnerable to inflammation caused by infarction or ischemic injury.We studied the role of E-po in regulation of expression and activation of the cell death-associated intracellular signaling components in cardiac myoblasts stimulated with the proinflammatory cytokine tumor necrosis factor (TNF)-alpha.Cardiac myoblasts isolated from canine embryonic hearts characterized by expression of my-ocardin A,a promyogenic transcription factor for cardiovascular muscle development were pretreated with Epo and then exposed to TNF-alpha.Compared to untreated cells,the Epo-treated cardiac myoblasts exhibited better morphology and viability.Immunoblotting revealed lower levels of active caspase- 3 and reductions in iNOS expression and NO production in Epo-treated cells.Furthermore,Epo pretreatment reduced nuclear translocation of NF-kap-paB and inhibited phosphorylation of inhibitor of kappa B(IkappaB) in TNF-alpha-stimulated cardiac myoblasts.Thus,Epo protects cardiac myocyte progenitors or myoblasts against the cytotoxic effects of TNF-alpha by inhibiting NF-kappaB-mediated iNOS expression and NO production and by preventing caspase-3 activation.In summary,clusterin and EPO are important factors that contribute to the survival and growth of cardiovascular cells and their progenitors.They may protect cardiovascular cells against apoptosis under various pathophysiological conditions in the heart and blood vessels.

SNPs and TFBS Associated with High Altitude Sickness

The rSNPs for the genes AKT3 (rs4590656), EGLN1 (rs480902), eNOS3 (rs1007311), and VEGFA (rs699947, rs13207311, rs1570360, rs2010963) have been significantly associated with the physiological parameters in high altitude sickness Han or Tibetan Chinese patients at the Qinghai-Tibetan plateau. The alleles of each rSNP have been found to create unique transcriptional factor binding sites for transcription factors that affect the process of hypoxia gene expression in this high altitude hypoxia environment.

Polarization sensitive optical coherence tomography with single input for imaging depth-resolved collagen organizations

Collagen organization plays an important role in maintaining structural integrity and determining tissue function.Polarization-sensitive optical coherence tomography(PSOCT)is a promising noninvasive three-dimensional imaging tool for mapping collagen organization in vivo.While PSOCT systems with multiple polarization inputs have demonstrated the ability to visualize depth-resolved collagen organization,systems,which use a single input polarization state have not yet demonstrated sufficient reconstruction quality.Herein we describe a PSOCT based polarization state transmission model that reveals the depth-dependent polarization state evolution of light backscattered within a birefringent sample.Based on this model,we propose a polarization state tracing method that relies on a discrete differential geometric analysis of the evolution of the polarization state in depth along the Poincare sphere for depth-resolved birefringent imaging using only one single input polarization state.We demonstrate the ability of this method to visualize depth-resolved myocardial architecture in both healthy and infarcted rodent hearts(ex vivo)and collagen structures responsible for skin tension lines at various anatomical locations on the face of a healthy human volunteer(in vivo).

动脉粥样硬化性高血压损伤动脉并加速血管细胞的凋亡与钙化

动脉粥样硬化和高血压是关系密切的慢性动脉疾病。在多种情况下,它们共存且相互作用,产生威胁生命的并发症,如心肌梗死和脑梗死。在动脉粥样硬化和高血压的多种病理变化中,动脉壁血管细胞凋亡增加、发生表型转变独具特色。有些分子通路在动脉粥样硬化病变的细胞组分变化中起作用。维持正常的血管结构和形态需要保持凋亡和增殖的平衡。在动脉粥样硬化和高血压的发病过程中,多种潜在的有害因素可能导致血管细胞功能异常或损伤。暴露于促动脉粥样硬化和高血压因素中的血管会由收缩型向合成型转变。降低血管细胞存活率和促进钙化是两个主要的病理变化,这些过程受影响不同表观因子表达的表观过程调节。阐明这些通路可能有助于发现动脉粥样硬化性高血压及其并发症,包括急性冠状动脉综合征的治疗新策略。