PTN FUNCTION IN INTIMAL THICKENING

PTN 在内膜增厚中的作用

• 批准号: 8644302
• 负责人: Prediman Krishan Shah
• 金额: $ 40.92万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-20 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8644302
• 关键词: Adopted; Adult; American; Animal Model; Anti-Inflammatory Agents; Anti-inflammatory; Apolipoprotein E; Applications Grants; Arteries; Atherosclerosis; Biological; Biological Models; Blood Circulation; Blood Vessels; Bone Marrow Transplantation; Cardiovascular Diseases; Cardiovascular Pathology; Cardiovascular system; Cause of Death; Cell Wall; Cells; Collection; Complementary DNA; Coronary; Coronary Artery Bypass; Coronary artery; Cultured Cells; Development; Embryonic Development; Endothelial Cells; Exhibits; Family suidae; Future; Gene Deletion; Gene Expression; Genes; Goals; Heterozygote; Homeostasis; Homozygote; Human; Hyperplasia; Implant; In Vitro; Inflammatory; Injury; Interferons; Interleukin-10; Knockout Mice; Knowledge; Lesion; MAPK3 gene; Mammary Arteries; Mediating; Mediator of activation protein; Messenger RNA; Molecular; Molecular Profiling; Myocardial Infarction; Natural regeneration; Outcome; Pathogenesis; Pathology; Phenotype; Play; Procedures; Protein Tyrosine Phosphatase; Publishing; Receptor Signaling; Recruitment Activity; Recurrence; Reporting; Research; Research Design; Resistance; Role; STAT1 gene; Series; Signal Pathway; Signal Transduction; Stem cells; Stimulation of Cell Proliferation; Stress; Testing; Tissues; Treatment Efficacy; United States; Vascular Diseases; Vascular remodeling; Veins; Woman; Wound Healing; angiogenesis; atherothrombosis; autocrine; base; cell type; cytokine; in vivo; insight; internal thoracic artery; loss of function; macrophage; men; monocyte; neointima formation; notch protein; novel; novel therapeutic intervention; paracrine; pleiotrophin; programs; receptor expression; response; tumor; tumorigenesis; vascular bed

DESCRIPTION (provided by applicant): This proposal grew out of our recent discovery of unique gene expression profiles of coronary and mammary arteries. There is extensive and compelling evidence demonstrating that there are underlying differences in propensity of different arteries to develop atherosclerosis. However, the underlying molecular mechanisms for these differences are completely unexplored. We have generated reciprocal cDNA collections of representing mRNA specific to porcine coronary vs. porcine mammary arteries. Pleiotrophin (PTN) gene was found to be specifically expressed in the coronary artery. PTN is a multifunctional cytokine that has been expressed by tumors and has been implicated in tumorigenesis. However, the cardiovascular activity of PTN remains unknown. Since PTN exhibits activities that are relevant to vascular pathologies, this application is based on the hypothesis that expression of PTN in arterial wall contributes to vascular pathologies and vascular remodeling. This project will characterize the role of PTN in neointimal formation by using in vitro and animal model systems. We propose interrelated studies that are designed to identify the cellular mechanism mediated by PTN that contributes to vascular remodeling, to evaluate the efficacy of intervention reducing PTN gene expression and its receptor expression, and to explore the PTN gene-specific mechanism of neointimal thickening. By studying how PTN contributes to vascular remodeling and identify the underlying cellular and molecular mechanism that mediates activity of PTN in the vessel wall, this application promises to take an important new step toward understanding how specific gene play a part in the pathogenesis of vascular disorders.

描述（由申请人提供）：该提案源于我们最近发现的冠状动脉和乳腺动脉的独特基因表达谱。有广泛而令人信服的证据表明，不同动脉发生动脉粥样硬化的倾向存在潜在差异。然而，这些差异的潜在分子机制完全未被探索。我们已经生成了代表猪冠状动脉和猪乳腺动脉特异性mRNA的互惠cDNA集合。发现多营养蛋白（PTN）基因在冠状动脉特异性表达。PTN是一种多功能细胞因子，已在肿瘤中表达，并与肿瘤发生有关。然而，PTN的心血管活性尚不清楚。由于PTN表现出与血管病变相关的活性，因此这项应用是基于PTN在动脉壁的表达有助于血管病变和血管重塑的假设。本项目将通过体外和动物模型系统来描述PTN在新生内膜形成中的作用。我们拟开展相关研究，旨在确定PTN介导的血管重构的细胞机制，评估降低PTN基因表达及其受体表达的干预效果，探索PTN基因特异性的内膜增厚机制。通过研究PTN如何促进血管重塑，并确定介导PTN在血管壁活性的潜在细胞和分子机制，这一应用有望为理解特定基因如何在血管疾病的发病机制中发挥作用迈出重要的新一步。

项目成果

Splenocytes seed bone marrow of myeloablated mice: implication for atherosclerosis.

• DOI: 10.1371/journal.pone.0125961
• 发表时间: 2015
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Wang L;Yang M;Arias A;Song L;Li F;Tian F;Qin M;Yukht A;Williamson IK;Shah PK;Sharifi BG
• 通讯作者: Sharifi BG

Oxidized LDL activated eosinophil polarize macrophage phenotype from M2 to M1 through activation of CD36 scavenger receptor.

• DOI: 10.1016/j.atherosclerosis.2017.05.011
• 发表时间: 2017-08
• 期刊: Atherosclerosis
• 影响因子: 5.3
• 作者: Qin M;Wang L;Li F;Yang M;Song L;Tian F;Yukht A;Shah PK;Rothenberg ME;Sharifi BG
• 通讯作者: Sharifi BG