Zusammenfassung
Arteriogenese, das Wachstum präformierter Arteriolen zu funktionellen Konduktanzarterien, kann im Tiermodell als experimenteller Grundlage zur Erforschung grundlegender Mechanismen induziert werden. Die für die Arteriogenese essenzielle Erhöhung der Schubspannung am Endothel der wachsenden Kollateralen wird durch einen Verschluss einer arteriellen Strombahn erzeugt. In diesem Beitrag werden zwei Modelle vorgestellt, bei denen Arteriogenese in der Peripherie stimuliert werden kann. Die Ligatur der A. femoralis am Hinterlauf der Maus ist ein standardisiertes Modell, bei dem nach arteriellem Verschluss Kollateralen in der Muskulatur des Hinterlaufs wachsen. Eine Weiterentwicklung dieses Modells stellt die Ligatur der A. femoralis in Kombination mit distal der Ligatur gelegener arteriovenöser Fistel dar. Durch diese Fistel wird der kollaterale Blutfluss direkt in die venöse Strombahn drainiert und die Schubspannung in den Kollateralen bleibt dauerhaft maximal erhöht. Mit diesem Modell kann Arteriogenese maximal und dauerhaft stimuliert werden.
Abstract
Arteriogenesis, the growth of preformed collateral arteries into functional conductance vessels, is a natural mechanism, which can be induced in animal models. Elevating the fluid shear stress on vessel endothelium is crucial for arteriogenesis and is generally induced by arterial occlusion. Two models to induce peripheral arteriogenesis are described. Ligating the femoral artery of the mouse hindlimb is a standardised model which leads to collateral growth in the thigh muscles. To enhance the effect of a simple ligature, the shunt-model, which combines the ligature with an arteriovenous fistula of a femoral artery and vein distal to the occlusion, may be employed. As a consequence the blood flow is drained directly into the venous system, causing chronically elevated shear stress and a maximal stimulus for arteriogenesis.
Literatur
Berk BC, Corson MA, Peterson TE, Tseng H (1995) Protein kinases as mediators of fluid shear stress stimulated signal transduction in endothelial cells: a hypothesis for calcium-dependent and calcium-independent events activated by flow. J Biomech 28:1439–1450
Brenes RA, Jadlowiec CC, Bear M et al (2012) Toward a mouse model of hind limb ischemia to test therapeutic angiogenesis. J Vasc Surg
Buschmann I, Schaper W (1999) Arteriogenesis versus angiogenesis: two mechanisms of vessel growth. News Physiol Sci 14:121–125
Busse R, Fleming I (1998) Regulation of NO synthesis in endothelial cells. Kidney Blood Press Res 21:264–266
Duan J, Murohara T, Ikeda H et al (2000) Hyperhomocysteinemia impairs angiogenesis in response to hindlimb ischemia. Arterioscler Thromb Vasc Biol 20:2579–2585
Eitenmuller I, Volger O, Kluge A et al (2006) The range of adaptation by collateral vessels after femoral artery occlusion. Circ Res 99:656–662
Ercin E, Gamperli O, Kaufmann P, Eberli FR (2007) Bland-White-Garland syndrome: extensive collaterals prevent ischaemia. Eur Heart J 28:1672–1672
Gudi S, Nolan JP, Frangos JA (1998) Modulation of GTPase activity of G proteins by fluid shear stress and phospholipid composition. Proc Natl Acad Sci U S A 95:2515–2519
Herzog S, Sager H, Khmelevski E et al (2002) Collateral arteries grow from preexisting anastomoses in the rat hindlimb. Am J Physiol Heart Circ Physiol 283:H2012–2020
Hsieh HJ, Cheng CC, Wu ST et al (1998) Increase of reactive oxygen species (ROS) in endothelial cells by shear flow and involvement of ROS in shear-induced c-fos expression. J Cell Physiol 175:156–162
Khachigian LM, Resnick N, Gimbrone MA Jr, Collins T (1995) Nuclear factor-kappa B interacts functionally with the platelet-derived growth factor B-chain shear-stress response element in vascular endothelial cells exposed to fluid shear stress. J Clin Invest 96:1169–1175
Li S, Kim M, Hu YL et al (1997) Fluid shear stress activation of focal adhesion kinase. Linking to mitogen-activated protein kinases. J Biol Chem 272:30455–30462
Li YS, Shyy JY, Li S et al (1996) The Ras-JNK pathway is involved in shear-induced gene expression. Mol Cell Biol 16:5947–5954
Limbourg A, Korff T, Napp LC et al (2009) Evaluation of postnatal arteriogenesis and angiogenesis in a mouse model of hind-limb ischemia. Nat Protoc 4:1737–1746
Luo MY, Yang BL, Ye F et al (2011) Collateral vessel growth induced by femoral artery ligature is impaired by denervation. Mol Cell Biochem 354:219–229
Naruse K, Sokabe M (1993) Involvement of stretch-activated ion channels in Ca2 + mobilization to mechanical stretch in endothelial cells. Am J Physiol 264:C1037–1044
Olesen SP, Clapham DE, Davies PF (1988) Haemodynamic shear stress activates a K+ current in vascular endothelial cells. Nature 331:168–170
Pipp F, Boehm S, Cai WJ et al (2004) Elevated fluid shear stress enhances postocclusive collateral artery growth and gene expression in the pig hind limb. Arterioscler Thromb Vasc Biol 24:1664–1668
Sayed A, Schierling W, Troidl K et al (2010) Exercise linked to transient increase in expression and activity of cation channels in newly formed hind-limb collaterals. Eur J Vasc Endovasc Surg 40:81–87
Schaper W (2009) Collateral circulation: past and present. Basic Res Cardiol 104:5–21
Shyy YJ, Hsieh HJ, Usami S, Chien S (1994) Fluid shear stress induces a biphasic response of human monocyte chemotactic protein 1 gene expression in vascular endothelium. Proc Natl Acad Sci U S A 91:4678–4682
Troidl C, Jung G et al (o J) The temporal and spatial distribution of macrophage subpopulations during arteriogenesis. Curr Vasc Pharmacol (Im Druck)
Troidl C, Nef H, Voss S et al (2010) Calcium-dependent signalling is essential during collateral growth in the pig hind limb-ischemia model. J Mol Cell Cardiol 49:142–151
Troidl C, Troidl K, Schierling W et al (2009) Trpv4 induces collateral vessel growth during regeneration of the arterial circulation. J Cell Mol Med 13:2613–2621
Troidl K, Tribulova S, Cai WJ et al (2010) Effects of endogenous nitric oxide and of DETA NONOate in arteriogenesis. J Cardiovasc Pharmacol 55:153–160
Zhuang ZW, Shi J, Rhodes JM et al (2011) Challenging the surgical rodent hindlimb ischemia model with the miniinterventional technique. J Vasc Interv Radiol 22:1437–1446
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Jung, G., Troidl, K., Apfelbeck, H. et al. Induktion von Arteriogenese in der Peripherie. Gefässchirurgie 17, 721–726 (2012). https://doi.org/10.1007/s00772-012-1083-7
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DOI: https://doi.org/10.1007/s00772-012-1083-7