Estrogen and the Cardiovascular System
The Karas lab's major research interest is the effect of estrogen on the cardiovascular system. More specifically, we focus on the molecular pathways that mediate estrogen's direct effects on vascular cells. Recent studies have shown that estrogen receptors in vascular cells can be activated in several novel ways, and several of these signaling pathways are actively being studied in the lab. Current studies are directed at understanding the role of rapid estrogen receptor signaling, and how this shares cross-talk with traditional genomic signaling pathways. The effect of estrogens on microRNA expression are also being studied. Ongoing, as well, are attempts to clone novel estrogen receptor-interacting proteins that regulate receptor activation.
Figure 1. The Karas laboratory studies the various signaling pathways by which estrogens regulate the biology of vascular cells and cardiomyoctye, focusing on emerging concepts in sex steroid hormone receptor signaling of potential importance in cardiovascular physiology. Newer concepts in SSHR action that are relatively unexplored in cardiovascular cells and tissues are depicted. Abbreviations: GFR, growth factor receptor; SSHR, sex steroid hormone receptor; SSHRE, SSH response element; CoA, coactivator; CoR, corepressor; NHR, non-SSHR nuclear receptors; TFs, transcription factors.
In addition to cell-based, molecular studies, the group uses whole animal, mouse models of cardiovascular diseases to study the effects of estrogen on the vascular system in vivo. In conjunction with the MCRI's mouse physiology core and mouse transgenic core laboratories, studies of estrogens effects on the response to vascular injury, on myocardial infarction, and on cardiac electrophysiology are all ongoing. These studies take advantage of the availability of several different genetically altered mouse models to define the molecular pathways that mediate estrogens effects.
Dr. Karas and his group also maintain an active interest in clinically-based studies focused on the regulation of vasomotor tone and on the effects of lipid lowering interventions and adverse events related to lipid-altering interventions.