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.

项目摘要--项目IV 随着高血压的发展，血压施加的力作用于血管结构。 导致血管系统的细胞成分发生病理变化。这些变化都有很好的描述 在血管内膜、中膜和外膜的细胞群中。然而，我们的知识中有一道鸿沟 高血压对第四血管层脂肪细胞及其前体细胞的影响 血管周围脂肪组织(PVAT)。脂肪细胞是PVAT的核心细胞，是血管活性的重要来源 支持血压控制的组件。项目IV的中心假设是血管机械 高血压时的作用力限制脂肪细胞前体细胞(AP)的成脂能力并促进其纤维化 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，我们 将决定这些力量如何与PVAT细胞外基质的硬度相互作用，从而影响成脂 血管周围AP的潜能，并控制其表型命运。在具体目标2中，我们将确定如何 高血压影响血管周围AP细胞的成脂能力，导致其纤维化程度增加 命运和PVAT脂肪细胞数量的减少。本项目(IV)将提供独特的机械信息 关于PVAT的AP和支持1)项目I发展的脂肪细胞生物学，因为这些细胞修改PVAT 硬度和脂肪膜如何适应血管机械力；和2)项目II和III，如 PVAT的脂肪生成、脂肪生成和纤维化对神经体液因子和免疫的反应和调节 细胞。我们期望阐明PVAT脂肪细胞前体和脂肪细胞作为血管整合因子的作用 Health将重新定义这些细胞在高血压发病机制和控制中的作用。