Diana Cruz-Topete, Ph.D.

Research summary

My Lab is interested in understanding the association between sex and stress hormones and heart disease. Heart failure is a leading cause of death in the United States. Events such as heart attacks are associated with a significant increase in the risk for sudden death and progression to heart failure. My research is focused on elucidating the link between stress and heart disease. Stress itself is considered a risk factor for cardiovascular disease. However, the molecular mechanisms underlying its effects are unknown.

Major areas of interest:

• Studying the crosstalk between sex hormones and stress signaling in myocardial infarction. Myocardial ischemia (MI) is the irreversible death of heart muscle secondary to prolonged lack of oxygen supply (ischemia). Ischemia leads to the loss of functional cardiomyocytes and subsequent death. Cardiomyocyte death leads to progressive ventricular dysfunction and eventually heart failure. Therefore, a detailed understanding of the cellular pathways of death and survival in MI is necessary to develop therapies to protect cardiomyocytes and preserve cardiac function. Glucocoricoids exert their actions by binding the glucocorticoid receptor (GR). Numerous observations have suggested that GR signaling is sexually dimorphic. Therefore, we are investigating the gender differences in MI in a genetically modified mouse model lacking GR in cardiomyocytes.
• Investigating the link between stress signaling and diet-induced obesity cardiomyopathy, with emphasis in sex differences. Obesity prevalence is higher in women than in men, therefore, it is important to understand the mechanisms by which gender influence obesity and its complications. Obesity leads to a variety of cardiac structural changes and hemodynamic alterations that may lead to cardiac dysfunction. Obesity cardiomyopathy typically occurs in patients with long-standing obesity. Prolonged high fat diet feeding in mice has been reported to recapitulate human cardiovascular complications associated with obesity/type 2 diabetes. Therefore, we are performing studies on the effects of high fat feeding in our genetically modified mouse model, which lacks GR in cardiomyocytes. We are particularly interested in understanding the effects of the crosstalk between sex hormones and GR signaling in obesity cardiomyopathy.

Major Research Areas

Nuclear receptors in cardiovascular disease, glucocorticoid receptor signaling in cardiomyocytes, estrogen receptors signaling crosstalk with GR in the heart, obesity and stress.