Pericyte Control of Junctional Blood Flow

周细胞对交界血流的控制

• 批准号: 10217229
• 负责人: Albert Louis Gonzales
• 金额: $ 14.87万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-17 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10217229
• 关键词: Affect; Architecture; Arteries; Biology; Blood Vessels; Blood capillaries; Blood flow; Caliber; Carbon Dioxide; Cardiac Muscle Contraction; Cardiovascular Diseases; Cardiovascular system; Cells; Complement; Computer Models; Contracts; Data; Development; Dimensions; Disease; Doctor of Philosophy; Effectiveness; Ensure; Environment; Erythrocytes; Extramural Activities; Faculty; Funding; Gases; Geometry; Health; Hyperemia; Individual; International; Light; Mentors; Metabolic; Molecular; Morphology; Mus; Muscle Cells; Neurodegenerative Disorders; Neurons; Nutrient; Outcome; Pathogenesis; Pathway interactions; Perfusion; Pericytes; Physiological; Physiology; Play; Process; Regulation; Research; Research Personnel; Resistance; Retina; Role; Shapes; Signal Transduction; Site; Skeletal Muscle; Smooth Muscle; Smooth Muscle Myocytes; Stochastic Processes; Structure; Techniques; Testing; Tissues; Training Programs; Universities; Vascular Diseases; Vermont; Work; arteriole; capillary bed; career; career development; cerebral capillary; constriction; in vivo; in vivo imaging; insight; member; multiphoton microscopy; muscle physiology; neurovascular coupling; new therapeutic target; next generation; novel; optogenetics; response; skills; tenure track; wasting

PROJECT SUMMARY To sustain the health of tissues in the body, the circulatory system needs to efficiently and continuously supply O2 and nutrients to every cell within the tissue. Capillaries, the site of gas exchange between circulating red blood cells (RBCs) and the surrounding tissue, constitute a majority of the vasculature. Yet, how—and in fact whether—the traverse of RBCs through the thousands of miles of branching capillaries to cells in need is a regulated remains unknown. This 5-year proposal focuses on pericytes located at capillary junctions and their role in regulating capillary blood flow. Pericytes, a type of contractile perivascular cell, have multiple projections that wrap around capillaries, and in so doing, can regulate the passage of RBCs. Preliminary data presented in this proposal show that pericytes, unlike other muscle cells, are capable of compartmentalized contraction and constriction of different branches of a junction. We hypothesize that pericytes play an important and novel role in structurally and dynamically changing the shape of junctions to insure the proper distribution of RBCs. In addition, the proposal will examine the molecular players involved in pericyte contraction, in particular, the mechanism that allows for a mode of contraction different from that of other muscle cells. The loss of pericytes is a hallmark of many cardiovascular and neurodegenerative illnesses, yet little is known about how the absence of pericytes affects blood flow and the pathogenesis of diseases. The current proposal will contribute to the career development of Dr. Albert L. Gonzales as he transitions from a postdoctoral associate to an independent researcher. Adding to his strong background in smooth muscle physiology, the candidate will develop new skills in state-of-the-art techniques, including in vivo multiphoton microscopy with next-generation genetically encoded Ca2+ indicators and optogenetic actuators. The University of Vermont is internationally recognized for its trainee development and productive research environment in vascular physiology. Mark Nelson, Ph.D. will serve as mentor for the candidate's scientific development. Dr. Nelson is a recognized leader in the field of vascular biology and has had 25 trainees who are now extramurally funded tenure-track faculty members at internationally and nationally ranked universities. To enhance the Candidate's training, the program additionally enlists internationally recognized experts, including Drs. Maiken Nedergaard, George Wellman, and Nikolaos Tsoukias. In this productive research environment, the candidate will establish a scientific niche and strengthen his transition to an independent research career.

项目摘要 为了维持身体组织的健康，循环系统需要有效和持续地 为组织内的每个细胞提供氧气和营养。Captured，循环气体之间交换的场所 红细胞（RBC）和周围组织构成了脉管系统的大部分。然而，事实上 红细胞穿过数千英里的毛细血管分支到达需要的细胞是否是一种 监管仍然未知。这个为期5年的提案重点是位于毛细血管连接处的周细胞及其 调节毛细血管血流的作用。周细胞是一种可收缩的血管周围细胞，具有多个突起 包裹在毛细血管周围，这样可以调节红细胞的通过。初步数据见 这一建议表明，周细胞与其他肌肉细胞不同，能够进行区室化收缩， 连接处的不同分支的收缩。我们假设周细胞在细胞内起着重要而新颖的作用， 在结构上和动态地改变连接的形状，以确保红细胞的适当分布。在 此外，该提案还将研究参与周细胞收缩的分子，特别是 一种允许与其他肌肉细胞不同的收缩模式的机制。周细胞的损失 是许多心血管和神经退行性疾病的标志，但很少有人知道缺乏 周细胞的功能影响血液流动和疾病的发病机制。 目前的建议将有助于阿尔伯特·L博士的职业发展。冈萨雷斯在他 从博士后助理到独立研究员加上他在平滑肌方面的强大背景 生理学，候选人将发展国家的最先进的技术，包括在体内多光子新技能 使用下一代遗传编码的Ca2+指示剂和光遗传学致动器的显微镜。大学 佛蒙特州是国际公认的实习生发展和生产研究环境， 血管生理学Mark纳尔逊博士将作为候选人科学发展的导师。博士 纳尔逊是血管生物学领域公认的领导者，已经有25名受训人员，他们现在是 资助国际和国内排名大学的终身教职员工。增强 候选人的培训，该计划还招募国际公认的专家，包括博士。 Nedergaard，乔治韦尔曼，和Nikolaos Tsoukias.在这种富有成效的研究环境中，候选人 将建立一个科学的利基，并加强他的过渡到一个独立的研究生涯。