Role of intercellular communication in the regulation of cardiac function

点击翻译按钮获取中文摘要

The primary function of a heart is to impart energy to blood to generate and sustain an arterial blood pressure necessary to provide adequate perfusion of organs. A human heart is composed of various cell types; however, the cardiomyocytes (CMs) and cardiac fibroblasts (CFs) constitute a significant mass of the heart and play a critical role in cardiac physiological function. The cardiomyocytes are terminally differentiated cells, and acute changes in cardiac function depend on the structural adaptations. Recently, the paracrine activity between cardiac cells has been shown to be a critical regulator of cardiac physiology. Vascular function is regulated primarily by endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and adventitial tissue. Most of the vessels in the human body are surrounded by the adipose tissue. The interactions among these cells/tissues are substantially involved in the vascular function. Recently, the perivascular adipocytes have shown to regulate vascular function by their paracrine activity on the ECs and SMCs. Cell-to-cell communication is essential for the development and environmental adaptation of multicellular organisms. Cells communicate with each other via extracellular molecules. Eukaryotic cells release complex structures called extracellular vesicles (EVs) which can affect cells that encounter these structures in a much complicated way. The EVs are broadly subdivided into different categories: microparticles, microvesicles, exosomes, etc. Exosomes are actively secreted endocytic nanovesicles with 30-100 nm diameter. Exosomes carry a composite cargo of molecules, including mRNAs, microRNAs, proteins, and lipids, and therefore plays a pivotal role in the exchange of genetic information. Emerging evidence suggests that recipient cells respond to exosome uptake with expressional and functional changes. Recently exosomes secreted from cardiac and vascular cells have shown to possess potent cell-function modulatory effects. Overarching Hypothesis: Exosomal intercellular communication plays a critical role in the regulation of cardiovascular physiology Our research proposal will outline specific aims and research questions that are designed to address the following specific objectives: 1. To characterize the cargo of CF-derived exosomes and identify their role in the regulation of cardiomyocyte function and cardiac physiology. 2. To characterize the cargo of perivascular adipocyte-derived exosomes and study their role in the regulation of vascular function. 3. To evaluate the sex-based differences in exosomal cargo and their effects on cardiovascular physiology. Our study will identify the exosomal cargo from various cardiovascular cell types and may provide a critical novel information about the role of intercellular communications in the cardiovascular physiology.