Defining the cellular and molecular mechanisms driving neointimal lesion growth in pulmonary hypertension

定义驱动肺动脉高压新内膜病变生长的细胞和分子机制

基本信息

  • 批准号:
    10594934
  • 负责人:
  • 金额:
    $ 66.83万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-03-20 至 2026-02-28
  • 项目状态:
    未结题

项目摘要

Project Summary/Abstract Pulmonary hypertension (PH) is a fatal disease of the pulmonary arteries with few supportive therapies and no cure. In PH, occlusive `neointimal lesions' grow within small pulmonary arteries and narrow vessel lumens, increasing pulmonary vascular resistance, ultimately resulting in right heart failure and death. Available PH therapies are vasodilators that do not target neointimal growth and neither prevent progression nor reverse disease. Understanding the biology of neointimal lesion growth – which cells are responsible for lesion expansion, and the pathways that control their proliferation – is key to the development of more effective therapies for pulmonary hypertension. In preliminary studies we find that proliferating neointima cells are adjacent to artery endothelial cells and have distinct gene expression that distinguishes them from cells located away from the endothelium. We hypothesize that a molecularly defined subset of neointimal cells located adjacent to the endothelium is the proliferating fraction that expands neointimal lesions, and that signals from the endothelium regulate lesion growth. Specific Aims: (1) Using proliferation tracking, genetic lineage tracing and ablation, identify and molecularly characterize the subset of neointimal cells whose proliferation is responsible for lesion growth. (2) Through bioinformatic analysis of single cell transcription in neointima and artery endothelial cells from mouse and human, identify candidate signals driving neointimal proliferation in PH and the core disease mechanisms shared between mouse and human. (3) Test the ability of a key candidate driver of neointimal proliferation for a role in lesion growth in multiple PH models. Here, by utilizing cutting edge technologies, genetics, and single cell approaches across multiple model systems, these experiments will provide a granular understanding of the cells and signals driving neointimal lesion expansion, adding substantially to the current knowledge surrounding the pathology of vascular remodeling in PH, findings we hope will ultimately lead to neointima-blocking treatment options.
项目总结/文摘

项目成果

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Maya Elise Kumar其他文献

Maya Elise Kumar的其他文献

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{{ truncateString('Maya Elise Kumar', 18)}}的其他基金

A clonal analysis of smooth muscle development in the mouse lung
小鼠肺平滑肌发育的克隆分析
  • 批准号:
    7446776
  • 财政年份:
    2007
  • 资助金额:
    $ 66.83万
  • 项目类别:
A clonal analysis of smooth muscle development in the mouse lung
小鼠肺平滑肌发育的克隆分析
  • 批准号:
    7630465
  • 财政年份:
    2007
  • 资助金额:
    $ 66.83万
  • 项目类别:
A clonal analysis of smooth muscle development in the mouse lung
小鼠肺平滑肌发育的克隆分析
  • 批准号:
    7275615
  • 财政年份:
    2007
  • 资助金额:
    $ 66.83万
  • 项目类别:

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