The Effect And Mechanism Of Pulsatile Low Shear Stress On Atherogenesis

It is well known that atherosclerosis is an inflammatory disease and shear stress plays a major role in determining the location, extent, and severity of the lesions. But what level of shear stress is critical and how pulsatile shear stress works in vivo in atherogenesis is not defined directly. To determine the effect of pulsatile low shear stress on atherogenesis and its inflammatory mechanism, based on an electromagnetic blood flowmeter and a mothed to determine the pulsatile shear stress from blood flow rate waveform and its software, we developed an in vivo pulsatile blood flow rate-shear stress determining system. Then,the left external carotid artery of 40 adult New Zealand White rabbits were ligated,which reduced the pulsatile shear stress of left common carotid significantly (for example, mean=21.16 ± 7.17 vs 3.13±2.28 dynes/cm2, p=2.176E-21)and did not change the pulsatile shear stress of right common carotid significantly. The pulsatile low or normal shear stress features of left and right common carotid lasted more than 12 weeks. After ligation, the rabbits were fed a special formulated hyperlipotic or a standard chow for 2,4,8 or 12 weeks (each group contained 5 rabbits), then thetwo common carotid ateries of each rabbit were harvested. Despite which diet the rabbits were fed, after 2,4,8,12 weeks in hyperliposis-fed rabbits and 8,12 weeks in normal-fed rabbits, atherosclerotic plaques were found underneath the endothelium of pulsatile-low-shear-stress left (not normal-shear-stress right) common carotid arteries. It clearly and directly demonstrated in vivo that pulsatile low shear stress plays a key role in atherogenesis. Worthmentionly, we first found that pure pulsatile low shear stress could result in atherosclerosis. We also tested the inflammatory factors CRPmRNA, MCP-1 mRNA, NF-kB> IL-1B, ICAM-1, VCAM-1 and PDGF-A, B, and found they were all up-regulated in pulsatile-low-shear-stress left (not right) common carotid arteries. These results support the pulsatile low shear stress-inflammatory response hypothesis of atherosclerosis, and also supply some theoretical and experimental foundations for atherosclerotic diseases prevention and treatment through arising the shear stress by biomedical engineering methods.