Role of intercellular communication in the regulation of cardiac function

心脏的主要功能是向血液输送能量，以产生和维持必要的动脉血压，以提供足够的器官灌注。人类的心脏由不同类型的细胞组成；然而，心肌细胞（CMs）和心脏成纤维细胞（CFs）构成了心脏的重要组成部分，在心脏生理功能中起着关键作用。心肌细胞是终末分化细胞，心功能的急性变化依赖于结构适应。近年来，心肌细胞间的旁分泌活性已被证明是心脏生理的重要调节因子。******血管功能主要由内皮细胞（ECs）、血管平滑肌细胞（VSMCs）和血管外组织调节。人体内的大部分血管都被脂肪组织包围着。这些细胞/组织之间的相互作用与血管功能密切相关。近年来，血管周围脂肪细胞通过其在内皮细胞和基质细胞上的旁分泌活性来调节血管功能。******细胞间的通讯对多细胞生物的发育和环境适应至关重要。细胞通过细胞外分子相互交流。真核细胞释放称为细胞外囊泡（EVs）的复杂结构，它可以以非常复杂的方式影响遇到这些结构的细胞。电动汽车大致可分为不同的类别：微粒、微泡、外泌体等。外泌体是活跃分泌的直径为30- 100nm的内吞纳米囊泡。外泌体携带多种分子，包括mrna、microrna、蛋白质和脂质，因此在遗传信息交换中起着关键作用。新出现的证据表明，受体细胞通过表达和功能变化响应外泌体的摄取。近年来，从心脏和血管细胞分泌的外泌体显示出具有强大的细胞功能调节作用。******总体假设：外泌体细胞间通讯在心血管生理调节中起关键作用******我们的研究计划将概述具体目标和研究问题，旨在解决以下具体目标：***1。表征cf来源外泌体的货物，并确定其在心肌细胞功能和心脏生理调节中的作用。研究血管周围脂肪细胞衍生外泌体的特征及其在血管功能调节中的作用。评估外泌体载物的性别差异及其对心血管生理的影响。******我们的研究将鉴定来自不同心血管细胞类型的外泌体货物，并可能提供关于细胞间通讯在心血管生理学中的作用的关键新信息。

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.