Mechanobiology of Cardiopulmonary Fibrosis

心肺纤维化的力学生物学

• 批准号: 10535459
• 负责人: WILLIAM D MERRYMAN
• 金额: $ 76.41万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-01-11 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10535459
• 关键词: Address; Animal Disease Models; Animal Model; Cardiopulmonary; Cells; Cicatrix; Communities; Development; Disease; Engineering; Faculty; Fibroblasts; Fibrosis; Future; Heart Valve Diseases; Heart failure; In Vitro; Laboratories; Myocardial Infarction; National Heart, Lung, and Blood Institute; Pathology; Patients; Phenotype; Positioning Attribute; Reagent; Research; Research Activity; Translating; cost; innovation; novel; prevent; programs; pulmonary arterial hypertension; right ventricular failure; treatment strategy

Summary Cardiopulmonary fibrosis is a unifying factor in multiple pathologies, including post myocardial infarction (MI) scarring that leads to heart failure, heart valve disease (HVD), and pulmonary arterial hypertension (PAH), among others. My laboratory explores fibroblast-driven, mechanobiological mechanisms of cardiopulmonary fibrotic remodeling and develops innovative strategies to prevent or treat these diseases. We focus on cardiopulmonary fibroblasts and how their unique phenotypic signatures can be targeted to halt their fibrotic machinery. We uniquely leverage our engineering expertise to address mechanobiological inputs that drive cardiopulmonary fibrosis, by effectively combining animal models of disease with primary cell in vitro studies. Our prior accomplishments provide strong evidence for future promise to bridge key gaps in our understanding that leads to development of novel treatment strategies. Initially, we focused on HVD, but have since expanded into general cardiopulmonary fibrosis, including PAH, which results in right heart failure, and fibrosis following MI. These new pursuits are complementary to our well-established research program in HVD and combining my laboratory’s NHLBI research portfolio would allow us to make rapid progress and translate our findings to patients by: 1) building on past accomplishments, while sustaining present efforts and being nimble enough to pursue opportunities presented in the course of research activities; 2) solidifying the value of cardiopulmonary mechanobiology and positioning my group to not only continue our research but to “seed” expertise more broadly in the NHLBI community; 3) maximizing common use of costly reagents and animal models more effectively; 4) supporting my group of eight trainees at steady state, including two junior faculty.

概括 心肺纤维化是多种病理的统一因素，包括心肌后 导致心力衰竭，心瓣疾病（HVD）和肺的梗塞（MI）疤痕 动脉高血压（PAH）等。我的实验室探索成纤维细胞驱动， 心肺纤维化重塑的机械生物学机制并发展创新 预防或治疗这些疾病的策略。我们专注于心肺成纤维细胞以及如何 它们独特的表型特征可以针对停止其纤维化机械。我们独特 利用我们的工程专业知识来解决驱动器的机械输入 心肺纤维化，有效地将疾病动物模型与原代细胞结合起来 体外研究。我们先前的成就为将来的承诺提供了有力的证据 我们的理解差距导致新的治疗策略的发展。最初，我们 专注于HVD，但此后已扩展到一般的心肺纤维化，包括PAH， 这导致正确的心力衰竭和MI后的纤维化。这些新的追求是 补充我们在HVD中建立良好的研究计划，并将我的实验室的研究结合在一起 NHLBI研究组合将使我们能够快速进步并将我们的发现转化为 患者：1）在过去的成就上建立过去，同时维持当前的努力和存在 足够灵活地购买研究活动过程中提供的机会； 2）固化 心肺机制的价值和定位我的小组不仅继续我们的 研究，但在NHLBI社区中更广泛地“种子”专业知识； 3）最大化常见 更有效地使用昂贵的试剂和动物模型； 4）支持我的八人组 稳态的学员，包括两个初级教师。