Cardiac Aging Lab
Dr. Groban, a Professor in the Department of Anesthesiology/Cardiothoracic Section at WFBMC has taken her echocardiographic skills gained in the clinical operating room arena and her background in cardiovascular physiology to study the underpinnings of diastolic dysfunction, the inability of the heart to fill adequately between beats due to impaired relaxation of the heart muscle. The condition is common in older adults because the heart and vessels normally stiffen with age. Dr. Groban’s lab continues to explore the causes, the implications, and the potential avenues for prevention and treatment of this age-related decline in diastolic function.
The incidence of diastolic dysfunction increases in women after menopause. It may lead to heart failure due to impaired ventricular filling secondary to abnormalities in myocardial relaxation, chamber compliance, and remodeling. While evidence suggests that estrogen may protect the premenopausal heart from the deleterious effects of hypertension and remodeling, the mechanisms involved are not completely understood. The overall goal of our research is to elucidate how estrogen modulates components of the cardiac renin angiotensin and nitric oxide systems in the development of diastolic dysfunction and left ventricular remodeling in a rodent model that emulates the postmenopausal diastolic phenotype. Using serial in vivo functional studies focused specifically on load independent measures of diastolic function (e’, and E/e’) along with biochemical, molecular, and immunocytochemical approaches, our group is effectively positioned to identify the sex-specific underpinnings of diastolic heart disease in older women.
(a) Jessup J, Lindsey SH, Wang H, Chappell MC, Groban L. Attenuation of salt-induced cardiac remodeling and diastolic dysfunction by GPER activation in female mRen2.Lewis rats. PLoS One. 2010 Nov 3;5(11):e15433
(b) Jessup JA, Zhang L, Chen AF, Presley TD, Kim-Shapiro DB, Chappell M, Wang H, Groban L. nNOS Inhibition Improves Diastolic Function and Reduces Oxidative Stress in Ovariectomized mRen2.Lewis Rats. Menopause 2011;18 (6), Feb 3 [ahead of print]
(c) Jessup JA, Zhang L, Wang H, Presley TD, Kim-Shapiro DB, Chen AF, Groban L. Tetrahydrobiopterin Restores Diastolic Function and Attenuates Superoxide Production in Ovariectomized mRen2.Lewis Rats. Endocrinology (accepted, in press).
Other research conducted in our laboratory focuses on mechanisms of age-related diastolic dysfunction in the male Brown Norway x Fisher rat, a strain that emulates “normal” aging. The cardioprotective potential of late life interventions, including exercise training, growth hormone supplementation, RAS inhibition, and omega-3 supplementation are also being examined.
Impairments in diastolic function represent a significant public health concern, particularly given the growing number of older persons in industrialized nations and the increased prevalence of heart failure with preserved ejection, or diastolic heart failure, among those older than 65 years of age. Currently, there are no proven pharmacological therapies to delay or reverse age-related diastolic dysfunction, independent of medically managing underlying co-morbidities such as hypertension, obesity, coronary atherosclerosis, and diabetes, which, in some cases, may be the root cause. Data obtained using these preclinical models may have profound implications for understanding and mitigating diastolic dysfunction in older persons.
Lab personnel and collaborators at taco outing
back row - Dr. Hao Wang, Marina Lin, Clarissa Chagas,
Jewel Jessup, Dr. Leanne Groban, Dr. Sarah Lindsey
front row-Kim Kassik