"Glycoprotein involvement in cardiac fibrobiast-myocyte communication "

“糖蛋白参与心脏成纤维细胞-肌细胞通讯”

• 批准号: 8183670
• 负责人: Jennifer E Van Eyk
• 金额: $ 32.8万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8183670
• 关键词: Acute myocardial infarction; Amino Acids; Angioplasty; Apoptosis; Architecture; Biological Markers; Blood Circulation; Blood flow; Cardiac; Cardiac Myocytes; Cardiovascular Diseases; Cell Communication; Cell Death; Cell surface; Cells; Cessation of life; Cicatrix; Clinical; Coculture Techniques; Communication; Complement; Complex; Coronary artery; Detection; Development; Diagnosis; Ensure; Environment; Extracellular Matrix; FarGo; Fibroblasts; Glycoconjugates; Glycoproteins; Gold; Heart; Heart failure; Hydrogen Peroxide; Hypoxia; Immunohistochemistry; Infarction; Injury; Instruction; Ischemia; Knowledge; Label; Lead; Link; Mass Spectrum Analysis; Methods; Monitor; Muscle; Muscle Cells; Myocardial; Myocardial Infarction; Myocardial Ischemia; Myocardium; Myofibroblast; Necrosis; Oligosaccharides; Oxidative Stress; Patients; Peptides; Phenotype; Play; Polysaccharides; Predisposition; Principal Investigator; Proteins; Proteome; Proteomics; Reaction; Regulation; Relative (related person); Reperfusion Therapy; Risk; Role; Sampling; Serum; Signal Transduction; Site; Slice; Specificity; Stress; Technology; Therapeutic Intervention; Tissues; Translating; Troponin; Validation; Ventricular Remodeling; Wound Healing; autocrine; base; cell type; clinical Diagnosis; clinically relevant; glycosylation; in vivo; injured; innovation; multiple reaction monitoring; novel; paracrine; response; response to injury

The blockage of coronary arteries can result in a heart attack (acute myocardial infarction; Ml) and permanent loss of cardiac muscle tissue. The resulting destruction of the complex cardiac architecture, formation of scar tissue, and myocardial remodeling increases risk of death. The heart's initial response to injury is synchronous and involves, in part, the reciprocal interaction between cardiac fibroblasts and myocytes, the two primary cell types comprising the heart. Recent findings suggest that soluble proteins secreted from cardiac fibroblasts and myocytes, also called the secretome, can modulate the infarct microenvironment (extracellular matrix, ECM). It is the cell surface that not only acts as a physical barrier but senses of the local ECM microenvironment that initiates the intrinsic cellular protective mechanisms upon injury. Thus, the cell-environment interface is the main site of this interplay. We hypothesize that fibroblasts are the linchpin and their respond to injury launches wound healing while also promoting myocyte survival. Fibroblasts accomplish this by altering the ECM microenvironment surrounding myocytes, especially those present in the infarct border zone. Many of the proteins comprising cell-environment interface are glycosylated. In this proposal, we will use a number of innovative methods to target, enrich, quantify (relative and absolute) and characterize the glycoproteome of the cell-environment interface of myocytes and fibroblasts alone and in co-culture with and without injury induced by H2O2. This includes using a novel twist when co-culturing, in which the proteins from one cell type have a covalent quantitative labeled which provides a mass spectrometry friendly marker to distinguishing the cell origin of each protein. We hypothesize that cell-specific glycoproteome comprising the cell-environment interface is responsible to the intrinsic susceptibility to H2O2 of myocytes compared to fibroblasts (SA 1). Furthermore, that a subset of the fibroblast-specific secreted proteins which are elevated in co-culture induces myocyte-protection and this protective phenotype is enhanced by the action of when fibroblast, themselves are injured (SA-2). Finally, we hypothesize that glycoproteins present in the microenvironment which are exclusively elevated in response of H2O2 will be detected in the circulation of patients with myocardial injury (ischemia) prior to the elevation of cardiac troponins (gold standard markers for Ml). In summary, the protein complement of the cell-environment interface has not been fully elucidated for either cardiac fibroblasts or myocytes. This knowledge is fundamental to developing clinical approaches to protect the heart and potentially provide robust clinical biomarkers RELEVANCE (See instructions); This is the first systematic analysis of the glycoproteins which comprise the secretome and cell surface of myocytes and fibroblast, two major cell types of the heart, for which their interaction is synergetic and can results in myocyte protection. These protective glycoproteins could be targets suitable for therapeutic intervention. As well, the myocardial and cardiac fibroblast specific hypoxic stimulated secreted proteins from cardiac fibroblasts and myocytes that circulating and are elevated in patients with myocardial ischemia

冠状动脉阻塞可导致心脏病发作（急性心肌梗死；Ml）