| Atherosclerosis has its patchy distribution in arteries and preferentially localize near side branches or curved vessels. Several studies provided evidence for a role of shear stress as the factor linking atherosclerotic plaque formation to its predilection sites. Shear stress is a friction force, in plane with the endothelial cell and induced by the movement of blood with respect to the endothelial layer, which is transmitted to the cell nucleus, affecting the expression of several genes. Cheng et al using a cast discovered that lowered shear stress (<4dyn/cm2) induces atherosclerotic plaque, whereas increased shear stress(10-70dyn/cm2) protects against atherosclerosis. The MMPs are a family of zinc-dependent endopeptidases whose function it is to break down numerous components of the ECM. MMP1, an interstitial collagenase, degrades fibrillar collagens type Ⅰ,Ⅱ,Ⅲ,Ⅴ,Ⅸ, and Ⅹ, that form the most abundant class of extracellular matrix proteins in the interstitium. TIMP-1is a more effective inhibitor for MMP-1.Our study is to investigate a new cast that may induces regions of lowered, increased, and lowered/oscillatory shear stresses in rabbit aorta abdominalis and amplified the relationship between shear stress and athrosclerosis,as well as MMP/TIMP.[Objective]To investigate a new cast that may induces regions of lowered, increased, and lowered/oscillatory shear stresses in rabbit aorta abdominalis and amplified the relationship between shear stress and athrosclerosis,as well as MMP-1/TIMP-1.[Methods](1)15male New Zealand white rabbits weighing2.0-2.5kg were fed on a high fat diet (120-140g/day) for16weeks after abdominal aortic balloon injury and placing placing the new cast around the aorta abdominalis2cm below arteria renalis.(2) The data was detected at two designated time points (2weeks,16weeks) including end diastolic diameter(Dr), systolic peak velocity(Vs), diastolic end velocit y(Vd), max velocity(Vm), Fasting plasma total cholesterol, LDL, HDL, and triglyceride levels were measured.(3) For oil red O, Sirius red, SMA,RAM-11, MMP-1and TIMP-1, the percentage of positively stained area as a function of the total plaque area was determined by computer-assisted morphometry of the plaques. Detect MMP-1/TIMP-1using immunohistochemical staining.[Results](1) In the cast, the complex lesion is half.(2) at the beginning and the end, TG is relatively0.97±0.21mmol/L and0.59±0.42mmol/L; TC is3.14±0.37mmol/L and6.04±1.20mmol/L; HDL-C is0.90±0.11mmol/L and1.22±0.13mmol/L; LDL-C is1.43±0.18mmol/L and1.86±0.37mmol/L.(2) Upstream from the cast, shear stress is relatively low (33.77±3.19dyn/cm2), caused by the flow-limiting stenosis induced by the cast. Within the cast, shear stress increases from relatively low to relatively high and then to relatively low because of the double-tapered shape of the cast. Downstream from the cast, shear stress is oscillatory(3) Upstream from the cast, lesions contain only thin layers of smooth muscle cells(9.55±2.76%) and collagen(15.03±7.23%) in the cap of the lesion, as well as significantly hgher lipid (37.62±7.32%) and macrophages(6.43±0.94%) whereas in downstream from the cast, smooth muscle cells(37.52±10.04%) and collagen-positive areas (43.74±10.29%) are more uniformly distributed in the intima. the lipid content (37.38±4.94%) and microphages(1.25±0.56%) are lower.(4) In the cast, the shear stress of the upstream may not protect against atherosclerosis.(5) MMP-1/TIMP-1is no difference in every group.[Conclusion](1) The new cast made complex lesion.(2) The new cast successfully induce the different shear stress in the rabbit aorta abdominalis. Lowered and oscillatory shear stress induces atherosclerotic plaque, whereas increased shear stress may not protect against atherosclerosis. Lowered shear stress lesions are unsteady, and oscillatory shear stress lesions are steady, which may not occur through the MMP-1/TIMP-1.(3)Haemodynamics is a factor which is independent of the lipid. |
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