Pericyte Control of Junctional Blood Flow

项目总结 为了维持体内组织的健康，循环系统需要高效和持续地 为组织内的每个细胞提供氧气和营养。毛细血管，循环之间气体交换的场所 红细胞(RBC)和周围组织构成了血管系统的主要部分。然而，如何--而且实际上 是否-红细胞穿越数千英里的分支毛细血管到达需要的细胞是一种 受监管的情况仍不得而知。这项为期5年的提案主要关注位于毛细血管连接处的周细胞及其 在调节毛细血管血流方面的作用。周细胞是一种收缩的血管周围细胞，有多个突起。 它包裹着毛细血管，在这样做的时候，可以调节红细胞的通过。提供的初步数据 这一建议表明，周细胞与其他肌肉细胞不同，能够隔断性收缩和 结合部的不同分支的收缩。我们假设周细胞扮演着一个重要而新颖的角色。 在结构上和动态地改变结合部的形状，以确保红细胞的适当分布。在……里面 此外，该提案将研究与周细胞收缩有关的分子角色，特别是 一种允许不同于其他肌肉细胞的收缩模式的机制。周细胞的丢失 是许多心血管和神经退行性疾病的标志，但人们对这种缺失的原因知之甚少 周细胞的数量影响血液流动和疾病的发病机制。 目前的提议将有助于阿尔伯特·冈萨雷斯博士在过渡期间的职业发展 从博士后助理到独立研究员。增加了他在流畅肌肉方面的强大背景 生理学方面，候选人将在最先进的技术方面发展新技能，包括体内多光子 具有下一代遗传编码的钙离子指示器和光遗传致动器的显微镜。这所大学 佛蒙特州大学以其实习生发展和富有成效的研究环境而受到国际认可 血管生理学。马克·纳尔逊博士将担任候选人科学发展的导师。Dr。 纳尔逊是血管生物学领域公认的领导者，他有25名实习生，现在他们都是 资助国际和国内排名大学的终身教职跟踪教员。为了增强 除了候选人的培训，该计划还招募了国际公认的专家，包括Maiken博士 尼德加德、乔治·威尔曼和尼古拉斯·祖克亚斯。在这个富有成效的研究环境中，候选人 将建立一个科学利基，并加强他向独立研究生涯的过渡。

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.