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 为了维持体内组织的健康，电路系统需要有效，连续 向组织中的每个细胞提供O2和营养。毛细管，循环之间的气体交换所在地 红细胞（RBC）和周围组织构成了大多数脉管系统。但是，如何 - 实际上 是否 - RBC穿过数千英里的分支毛细管到需要的细胞 受监管仍然未知。这个为期5年的提案着重于位于毛细管交界处的周细胞及其 控制毛细血管血流的作用。周细胞是一种收缩的血管周围细胞，有多个预测 围绕毛细血管，这样做可以调节RBC的通过。初步数据在 该提议表明，与其他肌肉细胞不同，周细胞能够分隔收缩和 连接的不同分支的收缩。我们假设周细胞起着重要而新颖的作用 在结构和动态更改连接的形状中，以确保RBC的正确分布。 此外，该提案将检查涉及周细胞收缩的分子参与者，特别是 允许一种与其他肌肉细胞不同的收缩方式的机制。丧失周细胞 是许多心血管和神经退行性疾病的标志，但知之甚少 周细胞会影响血流和疾病的发病机理。 当前的建议将有助于阿尔伯特·L·冈萨雷斯博士过渡时的职业发展 从博士后助理到独立研究人员。增加了他在平滑肌方面的强大背景 生理学，候选人将开发最新技术的新技能，包括体内多光子 具有下一代遗传编码的Ca2+指标和光遗传执行器的显微镜。大学 佛蒙特州因其受训者的发展和生产性研究环境而受到国际认可 血管生理。马克·尼尔森（Mark Nelson）博士将作为候选人科学发展的导师。博士 尼尔森是血管生物学领域的公认领导者，并有25名学员现在在外面露面 在国际和国家排名的大学的资助终身教师资助的教职员工。增强 候选人的培训，该计划还吸引了包括DRS在内的国际认可的专家。迈肯 Nedergaard，George Wellman和Nikolaos Tsoukias。在这个产品研究环境中，候选人 将建立科学的利基市场，并加强他向独立研究生涯的过渡。