Effect Of Angiotensin Converting Enzyme Inhibitors On Proliferation And Migration Of Medial Smooth Muscle Cells Of Rat Artery Injured By Balloon Chatheter

ACEI can decrease the incidence of restenosis of injured artery in animal model although the mechanism is still unknown. Intima hypertrophy (IH) after injury is caused by medial SMC proliferation and migration, however, the mechanism is unknown either. Proliferation is associated with many kinds of GF and migration is associated with metaloprotein elastase and collagenase that can degrade ECM. This study is intended in the hyperplastic process of SMC of injured artery the effect of ACEI on it and the elements involved in it and then the mechanism through which ACEI inhibits IH of medial SMC of injured artery.MaterialWistar rat; 2Fr balloon catheter; temocapril - HC1; BrdU;anti - BrdU anti - human PDGF - B anti - human PDGF( R) anti - human MMP - 1 anti -human MMP - 9, monoclonal anti - rat pancreatic elastase, goat anti digoxin alkaline phosphatase immunocomplex; digoxin signed rat pancreatic serine elastase II cDNA probe; substrate of pancreatic elastase.Method1. Animal model of restenosis: injury the carotid artery and the aortic artery respectively.2. Immunohistochemistry: carotid taken(1) Effect of ACEI on the proliferative process of medial SMCAssay BrdU labeling index (IBRD) of experiment and empty control groupat 12h and 1 -7d after injury.Assay IBRD of intimal or medial SMC of experiment and control group afterdifferent periodic administration .(2) Effect of ACEI on PDGF - B,PDGF(R) MMP - 1 MMP -9 and elastase of medial SMC of injured artery: assay IBRD of above items of experiment and control group in medial SMC 2, 3,5d after injury.3. Hybridization in situ; in carotid taken,assay positive cell index of elastase II mRNA expression of experiment and control group in medial SMC 2 3 5d after injury.4. Activity of elastase: in aortic taken, assay the activity of elastase of experiment and control group in medial SMC 2 3 5d after injury.5. Collagenase analysis in situ: in carotid taken, observe collagenase activity of experiment and control group in medial SMC 3d after injury.6. Assay the area of intima: in carotid taken, with software work out the area of intima of experiment and control group 10d after injury.7. Data and statistic analysis: Data is denoted with mean ?standard deviation. Compare between groups with Fisher test and in with t test, p < 0. 05 is taken as a drastic differentiation.Results1. Effect of ACEI on hyperplasia of medial SMC(1) Prolifertion of medial SMC after injury IBRD manifests biphasic increase with 2 peaks in the 2nd and the 5 day respectively with the former taller -5.35%.(2) Effect of ACEI on hyperplastic process of medial SMC after injury Result of administration in the 1st peak doesn t manifest drastic difference with that without administration and that in the 2nd.2. Effect of ACEI on PDGF-B PDGF(R) ,MMP -1 MMP-9 elastase III B elastase II mRNA expression elastase activity and collegenase activity The value of above items of experiment group is much smaller than that of control group in 2 3 and 5d after injury in media.3. Effect of ACEI on IH; Area of intima of experiment group is much less than that of control group l0d after injury.DiscussionACEI works through 2 ways: decrease Ang II and increase kinin level.ConclusionMedial SMC BrdU index of injured artery manifests a biphasic increase with 2 peaks in the 2nd and the 5th day. The 1st peak is necessary in IH. Through inhibiting the effect of GF released by SMC on SMC itself ACEI inhibits the 2nd GF release of SMC, expression of MMPelastase and collagenase and then the proliferation and migration of media SMC.