Center for Integrative Cardiovascular and Metabolic Disease

Center for Integrative Cardiovascular and Metabolic Disease

CICMD

A new scientific center at UF Health aims to unite cardiovascular and metabolic disease researchers.

Eric Krause in his lab with a student

Mission

The new Center for Integrative Cardiovascular and Metabolic Disease will support an emerging group of more than 25 UF faculty researching cardio-metabolic diseases, including Type 2 diabetes, obesity, chronic kidney disease, stroke and atherosclerosis. The center is expected to enrich research collaborations in publishing high-impact manuscripts and securing grant funding.

Director

Eric Krause

Eric Krause, Ph.D.

DIR & ASO PROF
Research Summary:

Stress, broadly defined as a real or perceived threat to homeostasis, activates neural circuits that alter the body’s physiology and behavior to ensure survival and well-being. The Krause Lab employs the rodent model to investigate how the central nervous system coordinates behavioral and physiological responses to stress. In particular, the lab studies how signals associated with dehydration impact the central pathways regulating stress responding and mood.

For example, loss of body fluids increases circulating levels of angiotensin II (ANGII), which activates the angiotensin type-1 receptors (AT1R) in various tissues to increase fluid intake, promote water and electrolyte retention and elevate blood pressure. Interestingly, the same neural circuits that regulate the influence of ANGII on hydromineral balance and cardiovascular function are also recruited during responding to psychological stress. Our studies have demonstrated that ANGII targets the brain via activation of AT1R in the subfornical organ (SFO), a specialized nucleus with an incomplete blood-brain-barrier, to coordinate the endocrine, cardiovascular and behavioral limbs of the stress response. These observations have led us to hypothesize that the AT1R in the SFO may be the site of convergence for the co-morbidity of psychopathology and cardiovascular disease.

In contrast to loss of body fluids, increasing plasma sodium concentration (pNa) elicits thirst by activating osmoreceptors in the brain. Acute increases in pNa suppress circulating ANGII and greatly elevate oxytocin levels centrally and systemically. Given that ANGII stimulates stress-responding and oxytocin is documented to have anti-stress properties especially when the stressor that is employed is social in nature, we predicted that acute osmotic dehydration would attenuate stress-responsiveness. Indeed, our studies have found that rats systemically administered a concentrated NaCl solution have decreased endocrine and cardiovascular responses to psychological stress exposure. Additionally, rats given NaCl engaged in more interactions when presented with unfamiliar conspecifics, suggesting that acute salt-loading decreases social anxiety. These observations have led to the hypothesis that acute increases in pNa attenuate stress-responsiveness, which may promote the social interactions that are encountered when engaging in drinking behavior. We are currently using this model to provide insight towards mechanisms underlying psychopathologies accompanied by cardiovascular irregularities like social phobias, anxiety and panic disorders.

My research utilizes an integrative approach towards investigating brain circuits governing physiology and behavior. We use chronic stress paradigms (i.e. visual burrow system or chronic variable stress) to model psychiatric disorders in rodents. Tract tracing, immunohistochemistry and in situ hybridization are used to characterize the neuroanatomical circuits mediating stress responding. Subsequently, we administer lentiviral vectors into brain nuclei that compose the circuit to inhibit the expression of targeted genes and reveal their contribution to stress responding and mood. To evaluate the limbs of the stress response, hormonal, cardiovascular and behavioral outcomes are assessed. Recently, we’ve obtained the angiotensin receptor flox mouse and plan to employ the cre-lox system to inhibit the expression of this receptor in select tissues.

Associate Directors

Michelle Cardel, Ph.D., R.D., an assistant professor of health outcomes & biomedical informatics in the UF College of Medicine

Rhonda Cooper-DeHoff, Pharm.D., M.S. an associate professor of pharmacotherapy and translational research in the UF College of Pharmacy

Michelle Gumz, Ph.D., an assistant professor of medicine in the UF College of Medicine