The Role of Galectin-3 in Cardiac Remodeling and Heart Failure

描述(由申请人提供)：这是波士顿马萨诸塞州综合医院的心脏病研究员Jennifer Ho博士的K23奖项的申请书。何博士将在心脏重塑和心力衰竭方面建立以患者为导向的临床研究。K23奖项将使何博士能够实现对她未来职业生涯至关重要的以下培训目标：(1)继续她在先进生物统计学方法方面的培训；(2)获得先进非侵入性心脏和血管成像方面的专业知识；(3)使心血管生理学的以患者为导向的干预研究变得容易；以及(4)建立独立的临床研究生涯。为了实现这些目标，何博士将与她的指导团队密切合作，团队成员包括她的主要导师、马萨诸塞州总医院心血管生理学和新陈代谢项目主任Thomas Wang博士，以及她的两位共同导师，Framingham心脏研究主任Daniel Levy博士和非侵入性心血管成像和遗传性心肌病专家Carolyn Ho博士。何博士的长期目标是使用信息丰富的生物标记物和非侵入性成像技术来定义导致明显心力衰竭的亚临床疾病表型，从而能够识别高危个体并采用针对潜在病理生理的治疗方法进行潜在治疗。她提议的研究将集中在这样一个潜在的途径上，Galectin-3。实验证据表明Galectin-3是心脏纤维化的重要介质，是心力衰竭的重要病理生理因素。作为生物标志物，Galectin-3还可以预测心力衰竭患者的预后。初步数据显示，Galectin-3可以预测社区中的心力衰竭事件。何博士的研究将集中于阐明Galectin-3与显性心力衰竭前的亚临床心血管表型的关系。具体地说，她将研究社区心脏和血管功能的关系(目标1)，以及肥厚型心肌病Galectin-3与心脏表型的关系，肥厚型心肌病是一种以心脏纤维化为标志的疾病(目标2)。最后，何博士将进行一项先导性随机安慰剂对照试验，研究Galectin-3抑制对Galectin-3水平升高的高血压患者胶原代谢和亚临床心血管表型的影响(目标3)。这项研究和培训计划将构成在高危人群中进行生物标记物引导的靶向治疗试验的基础，该试验将在K23奖项结束前在R01拨款申请中提出。

DESCRIPTION (provided by applicant): This is an application for a K23 award for Dr. Jennifer Ho, a cardiology research fellow at Massachusetts General Hospital, Boston. Dr. Ho is establishing a career in patient-oriented clinical research in cardiac remodeling and heart failure The K23 award will enable Dr. Ho to accomplish the following training goals critical to her future career: (1) to continue her training in advanced biostatistical methods; (2) to gain expertise in advanced noninvasive cardiac and vascular imaging; (3) to become facile with patient-oriented intervention studies in cardiovascular physiology; and (4) to establish an independent clinical research career. In order to achieve these goals, Dr. Ho will work closely with her mentoring team, consisting of her primary mentor, Dr. Thomas Wang, Director of the Program in Human Cardiovascular Physiology and Metabolism at Massachusetts General Hospital, and her two co-mentors, Dr. Daniel Levy, Director of the Framingham Heart Study, and Dr. Carolyn Ho, an expert in noninvasive cardiovascular imaging and genetic cardiomyopathies. Dr. Ho's long-term goals are to define subclinical disease phenotypes that lead to overt heart failure using informative biomarkers and non-invasive imaging, allowing the identification and potential treatment of at-risk individuals with therapies targeted at the underlying pathophysiology. Her proposed research will focus on one such potential pathway, Galectin-3. Experimental evidence suggests that Galectin-3 is an important mediator of cardiac fibrosis, an important contributor to the pathophysiology of heart failure. As a biomarker, Galectin-3 also predicts prognosis in patients with heart failure. Preliminary data shows Galectin-3 to predict incident heart failure events in the community. Dr. Ho's research will focus on elucidating the relation of Galectin-3 to subclinical cardiovascular phenotypes that precede overt heart failure. Specifically, she will study the relation to ventricular and vascular function in the community (Aim 1), and the relation of Galectin-3 to cardiac phenotypes in hypertrophic cardiomyopathy, a condition marked by cardiac fibrosis (Aim 2). Lastly, Dr. Ho will conduct a pilot randomized placebo-controlled trial t study the effect of Galectin-3 inhibition on collagen metabolism and subclinical cardiovascular phenotypes in hypertensive individuals with elevated Galectin-3 levels (Aim 3). This research and training plan will form the basis of a biomarker-guided targeted therapy trial in an at-risk population, to be proposed in an R01 grant application before the end of the K23 award.