Vascular Aging

Significant functional and structural abnormalities occur in the human vasculature with advancing age. Although these structural and functional changes may predispose humans for cardiovascular disease, the pathogenesis of these abnormalities is not well understood.  Hemodynamic forces associated with blood flow and pressure greatly influence the luminal dimensions and wall structure of the vasculature.  Hemodynamic shear stress, which provides an atheroprotective effect on blood vessels, has a central role in the regulation of luminal dimension.  Available data suggest that the sensitivity of the arterial wall to shear forces is progressively diminished with age.  A suppressed sensitivity of the vasculature to wall shear could be responsible for some of the aberrant remodeling observed with aging.   Such an altered responsiveness could be due to abnormalities in signal transduction, production of growth factors, responsiveness of the vascular cells, or degradation and synthesis of the extracellular matrix.

Our long-term goal is to establish the cellular and molecular basis for altered responsiveness to hemodynamic stimuli and vascular wall structural alterations which occur with aging.  Understanding these mechanisms will aid in the development of therapies for preventing and reversing these pathological changes.

Currently planned studies will investigate if abnormalities in shear-induced arterial wall remodeling are due to alterations in growth factor expression,  ability of cells to respond to growth factors, or the extracellular matrix.