[雙語翻譯]--生物醫(yī)學(xué)工程外文翻譯--內(nèi)皮剪切力在冠狀動脈粥樣硬化斑塊和血管重建進(jìn)展中的作用機(jī)制（原文）

1、REVIEWEndothelial shear stress in the evolution of coronary atherosclerotic plaque and vascular remodelling: current understanding and remaining questionsJolanda J. Wentzel1*, Yiannis S. Chatzizisis2,3*, Frank J.H. Gijse

2、n1, George D. Giannoglou3, Charles L. Feldman2, and Peter H. Stone21Biomedical Engineering, Department Cardiology, ErasmusMC, Rotterdam, The Netherlands; 2Cardiovascular Division, Brigham and Women’s Hospital, Harvard Me

3、dical School, Boston, MA, USA; and 31st Department of Cardiology, AHEPA University Hospital, Aristotle University Medical School, Thessaloniki, GreeceReceived 23 March 2012; revised 12 June 2012; accepted 25 June 2012; o

4、nline publish-ahead-of-print 29 June 2012Abstract The heterogeneity of plaque formation, the vascular remodelling response to plaque formation, and the consequentphenotype of plaque instability attest to the extraordinar

5、ily complex pathobiology of plaque development and pro-gression, culminating in different clinical coronary syndromes. Atherosclerotic plaques predominantly form in regionsof low endothelial shear stress (ESS), whereas r

6、egions of moderate/physiological and high ESS are generally pro-tected. Low ESS-induced compensatory expansive remodelling plays an important role in preserving lumen dimen-sions during plaque progression, but when the e

7、xpansive remodelling becomes excessive promotes continuedinflux of lipids into the vessel wall, vulnerable plaque formation and potential precipitation of an acute coronary syn-drome. Advanced plaques which start to encr

8、oach into the lumen experience high ESS at their most stenotic region,which appears to promote plaque destabilization. This review describes the role of ESS from early atherogenesis toearly plaque formation, plaque progr

9、ession to advanced high-risk stenotic or non-stenotic plaque, and plaque desta-bilization. The critical implication of the vascular remodelling response to plaque growth is also discussed. Currentdevelopments in technolo

10、gy to characterize local ESS and vascular remodelling in vivo may provide a rationale forinnovative diagnostic and therapeutic strategies for coronary patients that aim to prevent clinical coronarysyndromes.- - - - - - -

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12、 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Keywords Shear stress ? High-risk plaque ? Inflammation ? Vascular remodelling1. IntroductionAtherosclerotic plaques are regions in the arteria

13、l system charac-terized by intimal thickening with excessive build-up of oxidizedlow-density lipoprotein cholesterol accompanied by inflammatorycell infiltration, smooth muscle proliferation, and extracellularmatrix accu

14、mulation.1 Plaques prone to rupture (so-calledvulnerable plaques) are further characterized by the presenceof a large necrotic core covered by an inflamed thin fibrouscap.2 Rupture of a vulnerable coronary atheroscleroti

15、c plaqueis responsible for the majority of acute coronary events,3which are the leading cause of morbidity and mortality in theWestern world.Although the risk factors for atherosclerotic plaque formation, in-cluding high

16、 cholesterol, diabetes, and high blood pressure, are sys-temic in nature, plaques are located at specific sites in the arterialsystem. These sites include side-branches, the outer waist of bifurca-tions, or the inner cur

17、ve of arteries, where disturbed flow and lowendothelial shear stress (ESS) occur.4–7 In contrast, arterial regionsexposed to moderate/physiological ESS are protected fromatherosclerosis.Early observations on the relation

18、ship between ESS and plaque lo-calization were based mainly on autopsy material,8,9 and consequentlydid not allow investigation of the influence of ESS on atherosclerosis.The advent of three-dimensional (3D) reconstructi

19、on techniques forcoronary arteries in vivo,10 –13 based on biplane angiography and* Corresponding authors. J.J.W is at Biomechanics Laboratory, Biomedical Engineering, EE2322, ErasmusMC, PO Box 2040, 3000 CA Rotterdam, T

20、he Netherlands. Y.S.C is at First Department of Cardiology, AHEPA University Hospital, Aristotle University Medical School, 1 Stylp. Kuriakidi Street, 54636, Thessaloniki, Greece. Tel: +31 10 7044044 (J.J.W), +30 2310 99

21、4837 (Y.S.C.); fax: +31 10 7044720, Email: j.wentzel@erasmusmc.nl (J.J.W.); joc@med.auth.gr (Y.S.C.).Published on behalf of the European Society of Cardiology. All rights reserved. Figure 3B). Of note, the abso-lute cut

22、-off point for low ESS appears to be dependent on concomi-tant conditions as presented below (Section 3). Low ESS typicallyoccurs at the inner areas of curvatures and potentially at the upstreamshoulders of a stenosis. L

23、ow oscillatory ESS is bidirectional, with afluctuating magnitude between systole and diastole, resulting in alow time average (approximately ,1.0–1.5 Pa; Figure 3B). Low oscil-latory ESS occurs primarily downstream of st

24、enoses, at the lateralwalls of bifurcations and at the ostia of branches. High ESS is charac-terized by a significantly high time average (approximately .3.0 Pa)and occurs at the upstream and most stenotic site of the pl

25、aque.3. Dynamic nature of local ESSESS is a dynamic factor that changes in direction and magnitude withplaque formation and vascular remodelling.35 As a continuous vari-able, ESS covers a wide spectrum of values, from lo

26、w ESS to moder-ate/physiological ESS and to high ESS. The cut-off points defining low,moderate/physiological, and high ESS may vary among species, andamong vascular beds (e.g. femoral, carotid, and coronary arteries) int

27、he same species.36 Even in the same vascular location, ESS changesover time in response to several systemic and local factors. The sever-ity of systemic risk factors (e.g. hypercholesterolaemia) certainly influ-ences the

28、 effect of the local haemodynamic environment.Furthermore, the stage of atherosclerosis development, the remodel-ling response of the wall to plaque formation, as well as regional struc-tural and stiffness characteristic

29、s critically determine the local ESSenvironment and the subsequent natural history of individual athero-sclerotic lesions.33,35,374. Role of ESS in atherogenesis and early plaque formationIn straight arterial regions wit

30、h non-disturbed flow, where ESS varieswithin a moderate/physiological range, endothelial cells expressvarious atheroprotective genes, and decrease several pro-atherogenicones, leading to stability and quiescence.34 The r

31、ole of high ESS inearly atherosclerosis is not well investigated, but it appears to beatheroprotective. In contrast, in regions with low and disturbedflow where low ESS occurs, the atheroprotective genes are sup-pressed,

32、 while the pro-atherogenic genes are over-expressed,thereby promoting atherogenesis. Endothelial cells sense the locallow ESS stimuli through several mechanoreceptors located on theirsurface.32,34,38 These mechanorecepto

33、rs in turn trigger a network ofintracellular cascades, which culminate in the activation of transcrip-tion factors that transmigrate into the nucleus and shift gene and sub-sequently phenotypic endothelial cell expressio

34、n to an atheroscleroticstate.32,33,39 –42The largest body of evidence regarding the role of ESS in athero-sclerosis is derived from in vitro and in vivo animal studies. Althoughthese studies utilized fairly heterogeneous

35、 ESS patterns both in direc-tion and magnitude, which do not always resemble the real humanblood flow conditions, they provided the foundation and advancedour understanding concerning the role of ESS in atherosclerosis.F

36、igure 4 shows the implication of low ESS in the pathophysiology ofearly atherosclerosis.32,34 ESS induces endothelial dysfunction by re-ducing nitric oxide and increasing endothelin-1,43 provokes endothe-lial cell apopto

37、sis44 and conformational changes of endothelial cellsfrom fusiform to polygonal shape,45 induces subendothelial accumula-tion of low-density lipoprotein cholesterol,46 and modulates the oxi-dative transformation of low-d

38、ensity lipoprotein cholesterol bystimulating the production of reactive oxygen species.47 ThroughFigure 3 (A) Types of blood flow. (B) Types of ESS. Adapted from Chatzizisis et al.34J.J. Wentzel et al. 236by guest on Nov