The endogenous NOS system is augmented by ascorbate, sparing nitric oxide and also activating eNOS. Without it, stress fiber contraction occurs of the endothelial cells, detaching cells from one another and creating the leaky junctions described by Tarbell. When this occurs, the size exclusion barrier function to LDL, Lp(a), and other macromolecules that otherwise could not cross the lining under convective flow easily permeate into the subendothelial basement membrane collagen fibers, proteoglycans, and any medial smooth muscle layers that are then accessible.
Nitric oxide mediates tightening of the endothelial barrier by ascorbic acid.
Ascorbate stimulates endothelial nitric oxide synthase enzyme activity by rapid modulation of its phosphorylation status.
Through active modulation of a paracrine/autocrine small molecule factor, nitric oxide, ascorbic acid rapidly and potently inhibits endothelial permeability at physiologically achievable sub-millimolar concentrations, with the effect asymptotically increasing with diminishing returns up to 4mM ascorbate.
Subscribe to:
Posts (Atom)