Abstract

The candidate for the Paul B. Beeson Career Development Award in Aging was awarded the M.D. degree and received post-graduate fellowship training in cardiothoracic anesthesiology. The candidate has chosen to combine her cardiovascular background and interest in aging to study mechanisms of diastolic dysfunction related to aging. To this end, the candidate participated in the NIA Summer Research Institute and was subsequently awarded an R03 and the Dennis Jahnigen Career Development Award to examine the role of Insulin-like Growth Factor-1 (IGF-1) in Diastolic Dysfunction, which is the basis for the current career development plan. The proposed award will enable the candidate to accomplish the following objectives: 1) expand her scientific knowledge and research techniques in aging; 2) define a potential mechanism of diastolic dysfunction of aging; and 3) allow the candidate to independently plan and conduct basic research in aging. The research plan will facilitate the candidate's accomplishment of these goals by providing opportunities for advanced education in the physiology of aging, molecular and cellular biology, statistics, and a seminar on responsible conduct in research. The candidate will be directed in her efforts by an interdisciplinary group of investigators in hypertension, cardiology, physiology and pharmacology. Opportunities will be available for the candidate to present and discuss research in progress with young investigators affiliated with the Hypertension Center and the J. Paul Sticht Center of Aging and Rehabilitation. Within this environment, the candidate will characterize age-related changes in circulating and intracardiac renin-angiotensin (RAS) systems as they relate to the structural and functional changes in the aged rodent heart. The contribution of GH/IGF-1 senescence to diastolic dysfunction and the balance of RAS, specifically ACE and ACE2, will be explored. The functional role of RAS in the control of cardiac remodeling and diastolic performance will be examined using RAS-inhibition and GH supplementation. This award will provide a foundation for the development of the candidate as an independent clinician-investigator in aging, and the study results will ultimately contribute to improvement of the care of the elderly patient.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AG026764-02
Application #
7092612
Study Section
Special Emphasis Panel (ZAG1-ZIJ-9 (M3))
Program Officer
Kohanski, Ronald A
Project Start
2005-07-15
Project End
2010-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
2
Fiscal Year
2006
Total Cost
$169,560
Indirect Cost

  Institution

Name
Wake Forest University Health Sciences
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157

  Publications

Groban, Leanne; Wang, Hao; Machado, Frederico S M et al. (2012) Low glial angiotensinogen improves body habitus, diastolic function, and exercise tolerance in aging male rats. Cardiovasc Endocrinol 1:49-58
Kitzman, Dalane W; Groban, Leanne (2011) Exercise intolerance. Cardiol Clin 29:461-77
Sergeant, Susan; McQuail, Joseph A; Riddle, David R et al. (2011) Dietary fish oil modestly attenuates the effect of age on diastolic function but has no effect on memory or brain inflammation in aged rats. J Gerontol A Biol Sci Med Sci 66:521-33
Bharadwaj, Manish S; Strawn, William B; Groban, Leanne et al. (2011) Angiotensin-converting enzyme 2 deficiency is associated with impaired gestational weight gain and fetal growth restriction. Hypertension 58:852-8
Groban, L; Lin, M; Kassik, K A et al. (2011) Early-onset growth hormone deficiency results in diastolic dysfunction in adult-life and is prevented by growth hormone supplementation. Growth Horm IGF Res 21:81-8
Jessup, Jewell A; Zhang, Lili; Chen, Alex F et al. (2011) Neuronal nitric oxide synthase inhibition improves diastolic function and reduces oxidative stress in ovariectomized mRen2.Lewis rats. Menopause 18:698-708
Jessup, Jewell A; Zhang, Lili; Presley, Tennille D et al. (2011) Tetrahydrobiopterin restores diastolic function and attenuates superoxide production in ovariectomized mRen2.Lewis rats. Endocrinology 152:2428-36
Varagic, Jasmina; Ahmad, Sarfaraz; Brosnihan, K Bridget et al. (2010) Decreased cardiac Ang-(1-7) is associated with salt-induced cardiac remodeling and dysfunction. Ther Adv Cardiovasc Dis 4:17-25
Trask, Aaron J; Groban, Leanne; Westwood, Brian M et al. (2010) Inhibition of angiotensin-converting enzyme 2 exacerbates cardiac hypertrophy and fibrosis in Ren-2 hypertensive rats. Am J Hypertens 23:687-93
Jessup, Jewell A; Lindsey, Sarah H; Wang, Hao et al. (2010) Attenuation of salt-induced cardiac remodeling and diastolic dysfunction by the GPER agonist G-1 in female mRen2.Lewis rats. PLoS One 5:e15433

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