Anionic biopolymers as blood flow sensors.
The finding of flow-dependent vasodilation rests on the basic observation that with an increase in blood flow the vessels become wider, with a decrease the vascular smooth muscle cells contract. Proteoheparan sulphate could be the sensor macromolecule at the endothelial cell membrane-blood interface, that reacts on the shear stress generated by the flowing blood, and that informs and regulates the vascular smooth muscle cells via a signal transduction chain. This anionic biopolyelectrolyte possesses viscoelastic and specific ion binding properties which allow a change of its configuration in dependence on shear stress and electrostatic charge density. The blood flow sensor undergoes a conformational transition from a random coil to an extended filamentous state with increasing flow, whereby Na+ ions from the blood are bound. Owing to the intramolecular elastic recoil forces of proteoheparan sulphate the slowing of a flow rate causes an entropic coiling, the expulsion of Na+ ions and thus an interruption of the signal chain. Under physiological conditions, the conformation and Na+ binding proved to be extremely Ca(2+)-sensitive while K+ and Mg2+ ions play a minor role for the susceptibility of the sensor. Via counterion migration of the bound Na+ ions along the sensor glycosaminoglycan side chains and following Na+ passage through an unspecific ion channel in the endothelial cell membrane, the signal transduction chain leads to a membrane depolarization with Ca2+ influx into the cells. This stimulates the EDRF/NO production and release from the endothelial cells. The consequence is vasodilation.
Siegel
G
G
Institute of Physiology, Freie Universität Berlin, Germany.
Walter
A
A
Kauschmann
A
A
Malmsten
M
M
Buddecke
E
E
D015374:Biosensing Techniques; D002118:Calcium / Q000378:metabolism*; D004548:Elasticity; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000737:chemistry*; D006801:Humans; D008968:Molecular Conformation; D011509:Proteoglycans / Q000737:chemistry*; D012039:Regional Blood Flow; D012964:Sodium / Q000378:metabolism*; D014664:Vasodilation
D002118:Calcium; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D011509:Proteoglycans; D012964:Sodium