Adam Straub, PhD

Position:  Post Doctoral Fellow

Interests: Regulation of myoendothelial junction formation during vascular pathology

 

Altered heterocellular communication between endothelial cells (EC) and vascular smooth muscle cells (VSMC) is observed during vascular remodeling in disease states such as atherogenesis, hypertension, and peripheral ischemic disease. One way in which heterocellular communication is mediated is through myoendothelial junctions (MEJ), which are defined as the structural location where an EC or VSMC cellular extension protrudes through the internal elastic lamina, resulting in plasma membrane juxtaposition with the opposite cell type. An increase in the number of observed MEJs are strongly correlated with hypertension, however regulation of the formation of these structures in vascular diseases are not well understood. Recently, our lab has demonstrated that plasminogen activator inhibitor-1 (PAI-1) localizes to the MEJ and may be an important contributor to regulation of MEJ formation. Therefore, the focus of my research encompasses the role MEJs play during pathological arteriogenesis and vascular remodeling with respect to PAI-1 expression and function. We hypothesize that pathological arteriogenesis and vascular remodeling require PAI-1 regulated MEJ formation to stimulate proper EC and VSMC integration. To test this hypothesis, we will use 1) various mouse models such as the spinotrapezeus muscle arteriole ligation and the hindlimb ischemia models in PAI-1 knockout mice to determine the role of MEJs in arteriogenesis and 2) an in vitro vascular cell co-culture developed by our laboratory. Utilizing a combination of transmission and scanning electron microscopy as well as shRNA, we will be able to identify changes in the number of MEJ formed as well as their role in EC and VSMC integration. Understanding the contributing role(s) MEJs play in vascular pathologies will make for a clearer understanding of EC and VSMC integration.