Endothelial and Smooth Muscle Cell Development
Our laboratory is interested in how endothelial cells and smooth muscle cells develop during embryogenesis to form a mature, functional vasculature. In addition, changes in the function of vascular cells occur in vascular disease, and we are interested in the control of disease-related phenotypic alterations. Our current focus is the function of the Notch signaling pathway in these processes. Recently, we extended my focus to improve our understanding of perivascular adipose tissue (PVAT), which is essential in providing a specialized microenvironment for blood vessels. PVAT is contiguous with the vascular adventitia, providing a local source of secreted factors that influence the vessel wall. Our research is based on the hypothesis that molecular changes in PVAT, as a consequence of metabolic disease, result in profound effects on adjacent blood vessels that contribute to vascular dysfunction and susceptibility to atherosclerosis. Translational aspects of these studies will include evaluation of human PVAT and vessels to validate biomarkers of vascular disease susceptibility, identify novel therapeutic targets, and gain a mechanistic understanding of PVAT physiology. Our discoveries will provide innovative advances for cardiovascular science and clinical care.
Figure 1.Notch signaling in primary human smooth muscle cells promotes a highly contractile phenotype. Smooth muscle cells following Notch activation were stained to detect calponin (green) and actin (red).
Figure 2.Notch signaling plays a role in vascular endothelial cell sprouting. Shown are human endothelial cells forming sprouting extensions after seeding within a 3D matrix on a bead.
Figure 3. Perivascular adipose tissue adjacent to blood vessels creates a specialized vascular microenvironment. Top: Shown is the mouse thoracic aorta surrounded by perivascular adipose tissue (PVAT). Bottom: Mouse interscapular brown adipose tissue (BAT) is shown to indicate that PVAT has morphological similarity to BAT. Our goal is to understand how changes in PVAT with metabolic disease affects the vascular microenvironment and susceptibility to vascular pathology.
Figure 4. To better understand human vascular pathology, we study atherosclerotic lesions obtained from patient endarterectomy procedures (top). These specimens can be studied molecularly, and in addition, we can derive human diseased smooth muscle cells in culture (bottom) to study relevant signaling pathways.