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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

基本信息

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
项目类别：
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

项目摘要

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.

项目总结-项目四