Mechanobiology

Fluid mechanical forces generated by blood flow alter the metabolism of endothelium that line the blood vessel. In 1989, Scott Diamond published in Science an observation that fluid shear stress, instead of a biochemical signal, could control the genetic program of a living cell. The Diamond laboratory proceeded to identify the molecular mechanisms of cellular adaptation and dysfunction in mechanical environments. Mechanical deformations cause endothelial cell calcium mobilization (a regulator of metabolism) and that fluid shear increases endothelial c-fos protein (a regulator of gene transcription). Also, the production of the two most potent vasodilators, nitric oxide (NO) and prostacyclin, is highly coupled during mechanical force induction. In fact, high levels of shear stress shut down gene expression of the potent vasoconstrictor, endothelin, while the vasodilatory genes, eNOS and CNP, are upregulated. Finally, Diamond solved a 150-year old paradox in cardiovascular fluid dynamics called “poststenotic dilatation” where arteries hyperdilate downstream of a narrowing. Diamond discovered that NO is the mediator of this hydrodynamic maladaptation.

Currently, it remains unknown by what mechanisms exercise and gender lead to protection of the blood vessels. Our lab has discovered (Circulation Res., 2003) that fluid mechanical forces can actually act like the anti-inflammatory steroids(dexamethasone). Fluid shear stress activates the glucocorticoid receptor and turns on genes that contain glucocorticoid response elements in their promoter.

Publications