This proposal seeks to support the career development of Theodore Abraham, M.D., an Assistant Professor of Internal Medicine at the Mayo Medical School. The applicant's career goal is to develop an independent, dynamic, translational research program, integrating innovative imaging modalities and muscle physiology, within a vibrant and stimulating scientific environment. The KO8 award would protect the applicant from clinical duties, such as staffing the echocardiography laboratory, and allow full time research. The applicant plans to strengthen ongoing clinical research, and enhance his expertise and gain independence in muscle physiology, endocrinology and aging, under the mentorship of senior, established investigators. The scientific goal of this proposal is to examine the role of testosterone in the development of age-related diastolic dysfunction. Aging is associated with diastolic dysfunction that results in significant morbidity and mortality in the elderly. Since testosterone levels decrease with age, it is hypothesized that testosterone deficiency forms the pathophysiologic basis for the development of diastolic dysfunction, and that testosterone replacement alleviates diastolic dysfunction in the elderly. Using innovative imaging techniques, the applicant has recently introduced novel concepts with obvious implications in age-related diastolic dysfunction. This proposal seeks to expand on these observations, and plans to: a) in the setting of a NIH funded, randomized, double-blind, placebo-controlled clinical study (applicant is the project leader for the cardiovascular component), test whether testosterone deficiency worsens, and replacement alleviates, diastolic dysfunction in the elderly; b) in the same setting, examine whether testosterone mediates diastolic function through regulation of peripheral hemodynamics; and c) in an animal model, explore possible underlying cellular mechanisms of testosterone-mediated diastolic dysfunction, specifically intracellular calcium regulation. The proposed experiments will generate significant new knowledge pertaining to age-related diastolic dysfunction, specifically with regard to the interactions between hormonal changes and ventricular mechanics. Most importantly, potential direct clinical benefits of this research include early detection, improved and novel therapy, and better clinical outcomes for age-related diastolic dysfunction.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AG022554-05
Application #
7431649
Study Section
National Institute on Aging Initial Review Group (NIA)
Program Officer
Nayfield, Susan G
Project Start
2004-09-30
Project End
2010-05-31
Budget Start
2008-06-01
Budget End
2010-05-31
Support Year
5
Fiscal Year
2008
Total Cost
$119,853
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Olsen, Niels Thue; Dimaano, Veronica L; Fritz-Hansen, Thomas et al. (2013) Hypertrophy signaling pathways in experimental chronic aortic regurgitation. J Cardiovasc Transl Res 6:852-60
Liang, Hsin-Yueh; Cheng, Alan; Chang, Kuan-Cheng et al. (2011) Influence of atrial function and mechanical synchrony on LV hemodynamic status in heart failure patients on resynchronization therapy. JACC Cardiovasc Imaging 4:691-8
Abraham, Theodore P; Liang, Hsin-Yueh (2009) Stress echocardiography: diastole to the rescue. J Am Coll Cardiol 53:706-8
Abraham, Theodore P; Jones, Michelle; Kazmierczak, Katarzyna et al. (2009) Diastolic dysfunction in familial hypertrophic cardiomyopathy transgenic model mice. Cardiovasc Res 82:84-92
Santaularia-Tomas, Miguel; Abraham, Theodore P (2009) Criteria predicting response to CRT: is more better? Eur Heart J 30:2835-7
Tops, Laurens F; Prakasa, Kalpana; Tandri, Harikrishna et al. (2009) Prevalence and pathophysiologic attributes of ventricular dyssynchrony in arrhythmogenic right ventricular dysplasia/cardiomyopathy. J Am Coll Cardiol 54:445-51
Abraham, Theodore P; Pinheiro, Aurelio C (2008) Speckle-derived strain a better tool for quantification of stress echocardiography? J Am Coll Cardiol 51:158-60
Abraham, Theodore P; Dimaano, Veronica L; Liang, Hsin-Yueh (2007) Role of tissue Doppler and strain echocardiography in current clinical practice. Circulation 116:2597-609
Liang, Hsin-Yueh; Cauduro, Sanderson; Pellikka, Patricia et al. (2006) Usefulness of two-dimensional speckle strain for evaluation of left ventricular diastolic deformation in patients with coronary artery disease. Am J Cardiol 98:1581-6
Takemoto, Yasuhiko; Pellikka, Patricia A; Wang, Jianwen et al. (2005) Analysis of the interaction between segmental relaxation patterns and global diastolic function by strain echocardiography. J Am Soc Echocardiogr 18:901-6