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学的统一因素，包括心肌病后 梗死 (MI) 疤痕会导致心力衰竭、心脏瓣膜疾病 (HVD) 和肺部疾病 动脉高血压（PAH）等。我的实验室探索成纤维细胞驱动的 心肺纤维化重塑的机械生物学机制并开发创新 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被靶向阻止其纤维化机制。我们独一无二 利用我们的工程专业知识来解决驱动的机械生物学输入 心肺纤维化，通过将疾病动物模型与原代细胞有效结合 体外研究。我们之前的成就为未来承诺弥合关键问题提供了强有力的证据 我们理解上的差距导致了新治疗策略的发展。最初，我们 专注于 HVD，但后来扩展到一般心肺纤维化，包括 PAH， 这会导致右心衰竭和心肌梗死后的纤维化。这些新的追求是 补充我们在 HVD 方面完善的研究计划，并结合我实验室的 NHLBI 研究组合将使我们能够取得快速进展并将我们的发现转化为 患者可以通过以下方式：1）以过去的成就为基础，同时保持当前的努力和 足够灵活地抓住研究活动过程中出现的机会； 2）凝固 心肺力学生物学的价值并使我的团队不仅继续我们的研究 研究，但为了在 NHLBI 社区中更广泛地“播种”专业知识； 3）最大化共同点 更有效地使用昂贵的试剂和动物模型； 4）支持我的八人小组 处于稳定状态的受训人员，包括两名初级教师。