The perivascular adipocyte: integrating mechanical and structural cues into vasoactive function

血管周围脂肪细胞：将机械和结构信号整合到血管活性功能中

• 批准号: 10543530
• 负责人: Genaro Andres Contreras
• 金额: $ 40.22万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-22 至 2026-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10543530
• 关键词: Adipocytes; Adipose tissue; Adult; Affect; Anatomy; Animal Experiments; Animals; Blood Pressure; Blood Vessels; Cardiovascular Diseases; Cells; Cessation of life; Cues; Data; Development; Exposure to; Extracellular Matrix; Extracellular Structure; Fatty acid glycerol esters; Female; Fibroblasts; Fibrosis; Functional disorder; Health; High Fat Diet; Hypertension; Hypertrophy; Immune; Incidence; Intervention; Knowledge; Mechanics; Modeling; Modification; Mus; Obesity; Overweight; Pathogenesis; Pathologic; Patients; Pattern; Pericytes; Phenotype; Piezo 1 ion channel; Platelet-Derived Growth Factor alpha Receptor; Population; Prevalence; Process; Rattus; Resistance; Role; Shapes; Signal Transduction; Source; Structure; Testing; Tissues; Tunica Adventitia; Tunica Intima; Tunica Media; Variant; Vascular remodeling; adipocyte biology; adipokines; blood pressure control; cell growth; dietary control; experimental study; fibroblast growth factor 9; hypertension control; in vitro Model; lipid biosynthesis; male; mechanical force; mechanical signal; migration; normotensive; novel; physical property; pressure; progenitor; response; stem cells; synergism

Project Summary – Project IV As hypertension develops, the forces exerted by blood pressure are applied to the vessels' structures inducing pathological changes in the cellular components of the vasculature. These changes are well described in cell populations of the vascular tunicas intima, media, and adventitia. However, there is a gap in our knowledge of hypertension's impact on adipocytes and their progenitors in the fourth vessel layer, the tunica adiposa or perivascular adipose tissue (PVAT). Adipocytes are the core cells of PVAT and are a crucial source of vasoactive components that support blood pressure control. The central hypothesis of Project IV is that vascular mechanical forces during hypertension limit the adipogenic capacity of adipocyte progenitors (AP) and enhance their fibrotic responses, leading to PVAT dysfunction. Project IV will investigate the effects of vascular mechanical forces on PVAT function. In Specific Aim 1, we will determine how these forces interact with the stiffness of the PVAT extracellular matrix to affect the adipogenic potential of perivascular AP and govern their phenotype fate. In Specific Aim 2, we will determine how the adipogenic potential of perivascular AP cells is impacted by hypertension leading to an increase in their fibrotic fate and a reduction in PVAT adipocyte populations. This project (IV) will provide unique mechanistic information on PVAT's AP and adipocyte biology to support the development of 1) Project I, as these cells modify PVAT stiffness and how the tunica adiposa adapts to vascular mechanical forces; and 2) Projects II and III, as adipogenesis, lipogenesis, and fibrosis in PVAT respond to and modulate neurohumoral factors and immune cells. We expect that elucidating the role of PVAT adipocyte progenitors and adipocytes as integrators of vascular health will redefine the role of these cells in the pathogenesis and control of hypertension.

项目概要-项目四 随着高血压的发展，血压施加的力作用于血管结构 诱导脉管系统的细胞成分的病理变化。这些变化被描述得很好 在血管内膜、中膜和外膜的细胞群中。然而，我们的知识有一个缺口 高血压对第四血管层（图尼卡脂膜或）中脂肪细胞及其祖细胞的影响 血管周围脂肪组织（PVAT）。脂肪细胞是PVAT的核心细胞，是血管活性物质的重要来源。 支持血压控制的组件。项目IV的中心假设是， 高血压期间的压力限制了脂肪祖细胞（AP）的成脂能力，并增强了它们的纤维化 反应，导致PVAT功能障碍。 项目IV将研究血管机械力对PVAT功能的影响。在具体目标1中， 将确定这些力如何与PVAT细胞外基质的刚度相互作用，以影响成脂细胞的成脂性。 潜在的血管周围AP和支配他们的表型命运。在具体目标2中，我们将确定 血管周围AP细胞的成脂潜力受到高血压的影响，导致其纤维化增加。 命运和PVAT脂肪细胞群的减少。该项目（IV）将提供独特的机械信息 研究PVAT的AP和脂肪细胞生物学，以支持1）项目I的开发，因为这些细胞修饰PVAT 硬度以及图尼卡脂膜如何适应血管机械力;以及2）项目II和III， PVAT中的脂肪生成、脂肪生成和纤维化响应并调节神经体液因子和免疫调节因子。 细胞我们希望阐明PVAT脂肪祖细胞和脂肪细胞作为血管整合剂的作用， 健康将重新定义这些细胞在高血压发病机制和控制中的作用。