Role of intercellular communication in the regulation of cardiac function

心脏的主要功能是将能量传递给血液，以产生和维持提供器官的充分灌注所必需的动脉血压。人类心脏由多种细胞类型组成;然而，心肌细胞（CM）和心脏成纤维细胞（CF）构成心脏的重要质量，并在心脏生理功能中发挥关键作用。心肌细胞是终末分化的细胞，心脏功能的急性变化依赖于结构适应。近年来，心脏细胞间的旁分泌活动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（EC）、血管平滑肌细胞（VSMCs）和外膜组织调节。人体内的大部分血管都被脂肪组织所包围。这些细胞/组织之间的相互作用实质上涉及血管功能。近年来研究发现，血管周围脂肪细胞通过对内皮细胞和平滑肌细胞的旁分泌调节血管功能。细胞间通讯对于多细胞生物的发育和环境适应是必不可少的。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（EV）的复杂结构，其可以以非常复杂的方式影响遇到这些结构的细胞。EV被广泛地细分为不同的类别：微粒、微泡、外泌体等。外泌体是具有30-100 nm直径的主动分泌的内吞纳米囊泡。外泌体携带分子的复合货物，包括mRNA、microRNA、蛋白质和脂质，因此在遗传信息的交换中起着关键作用。新出现的证据表明，受体细胞对外泌体摄取的反应是表达和功能的变化。最近，从心脏和血管细胞分泌的外泌体显示出具有有效的细胞功能调节作用。过度假设：外泌体细胞间通讯在心血管生理的调节中起着至关重要的作用我们的研究计划将概述具体的目的和研究问题，旨在解决以下具体目标：1.目的：1.研究CF源性外泌体的转运特性，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来源的exosomes的运载物，并探讨其在血管功能调节中的作用.为了解外泌体转运蛋白的性别差异及其对心血管生理的影响，本研究将从不同类型的心血管细胞中鉴定外泌体转运蛋白，为研究细胞间通讯在心血管生理中的作用提供新的信息。

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 physiologyOur 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.