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.
Heart failure is often diagnosed late in the course of the disease, when prognosis is poor. Strategies that identify and target high-risk individuals earlier in the disease course may prevent complications associated with heart failure. This proposal seeks to study one such potential pathway, which may allow the identification of at-risk individuals and guide potential targeted treatment to delay the onset of heart failure.
|Ho, Jennifer E; Yin, Xiaoyan; Levy, Daniel et al. (2014) Galectin 3 and incident atrial fibrillation in the community. Am Heart J 167:729-34.e1|
|Ayalon, Nir; Gopal, Deepa M; Mooney, Deirdre M et al. (2014) Preclinical left ventricular diastolic dysfunction in metabolic syndrome. Am J Cardiol 114:838-42|
|Ho, Jennifer E; Arora, Pankaj; Walford, Geoffrey A et al. (2014) Effect of phosphodiesterase inhibition on insulin resistance in obese individuals. J Am Heart Assoc 3:e001001|
|Ho, Jennifer E; Larson, Martin G; Ghorbani, Anahita et al. (2014) Long-term cardiovascular risks associated with an elevated heart rate: the Framingham Heart Study. J Am Heart Assoc 3:e000668|
|Rienstra, Michiel; Yin, Xiaoyan; Larson, Martin G et al. (2014) Relation between soluble ST2, growth differentiation factor-15, and high-sensitivity troponin I and incident atrial fibrillation. Am Heart J 167:109-115.e2|
|Gopal, Deepa M; Larson, Martin G; Januzzi, James L et al. (2014) Biomarkers of cardiovascular stress and subclinical atherosclerosis in the community. Clin Chem 60:1402-8|
|Ho, Jennifer E; Chen, Wei-Yu; Chen, Ming-Huei et al. (2013) Common genetic variation at the IL1RL1 locus regulates IL-33/ST2 signaling. J Clin Invest 123:4208-18|
|Rhee, Eugene P; Ho, Jennifer E; Chen, Ming-Huei et al. (2013) A genome-wide association study of the human metabolome in a community-based cohort. Cell Metab 18:130-43|
|Ho, Jennifer E; Hwang, Shih-Jen; Wollert, Kai C et al. (2013) Biomarkers of cardiovascular stress and incident chronic kidney disease. Clin Chem 59:1613-20|