Effects of Stenting the Parent Artery on Aneurysm Filling and Gene Expression of Various Potential Factors Involved in Healing of Experimental Aneurysms
Restricted accessResearch articleFirst published online December, 2006
Effects of Stenting the Parent Artery on Aneurysm Filling and Gene Expression of Various Potential Factors Involved in Healing of Experimental Aneurysms
Intracranial stents are increasingly used in the endovascular treatment of aneurysms, but very little is known regarding their effect on the cellular and molecular evolution of aneurysms.
Bilateral venous pouch lateral wall carotid aneurysms were created in 20 dogs. All dogs then underwent angiography and balloon-expandable stenting of one aneurysm four to six weeks later. Fifteen dogs underwent aneurysm harvesting at one day (n=3), four days (n=4), seven days (n=3), and 14 days (n=5) for mRNA expression analysis, using axial sections taken from the aneurysm neck and fundus for RT-PCR amplification of four cytokines or growth factors: TNF-a, TGF-b1, MCP-1, and PDGF-BB; two adhesion molecules: VCAM-1 and PECAM-1; five matrix modifying agents; MMP-2, 9, TIMPs 1, 3, 4, and two cellular markers: CD34 and a-SMA.
Five other dogs, sacrificed at 12 weeks, were examined for extent of filling of the aneurysm neck with organized tissue and for neointima formation at the aneurysm ostium. Angiography was performed prior to sacrifice in all animals, and compared with initial studies. Eleven out of 20 stented aneurysms showed a favorable angiographic evolution, while none of the 20 non-stented aneurysms improved (p=0.001). Pathology showed partially occluded aneurysms, with neointima formation around the stent struts. Observed trends in mRNA expression, that stenting increased expression of genes involved in organization and neointima formation, agreed with experimental hypotheses, but differences between stented and non-stented aneurysms did not reach statistical significance.
Parent vessel stenting was associated with angiographic improvement of aneurysm appearance. Modifications in mRNA expression patterns following stenting deserve further study to better establish potential molecular targets to promote aneurysm healing.
MolyneuxA: International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: A randomised trial. Lancet, 360 (9342): 1267–1274, 2002.
2.
RaymondJ: Long-term angiographic recurrences after selective endovascular treatment of aneurysms with detachable coils. Stroke, 34 (6): 1398–1403, 2003.
3.
CloftHJKallmesDF: Aneurysm packing with HydroCoil Embolic System versus platinum coils: Initial clinical experience. Am J Neuroradiol25(1): 60–62, 2004.
4.
LanzinoG: Emerging concepts in the treatment of intracranial aneurysms: Stents, coated coils, and liquid embolic agents. Neurosurgery57(3): 449–459; discussion 449–459, 2005.
5.
MolyneuxAJ: Cerebral Aneurysm Multicenter European Onyx (CAMEO) trial: Results of a prospective observational study in 20 European centers. Am J Neuroradiol25(1): 39–51, 2004.
6.
MurayamaY: Matrix and bioabsorbable polymeric coils accelerate healing of intracranial aneurysms: Long-term experimental study. Stroke34(8): 2031–2037, 2003.
7.
MurayamaY: Bioabsorbable polymeric material coils for embolization of intracranial aneurysms: A preliminary experimental study. J Neurosurg94(3): 454–463, 2001.
8.
HorowitzMB: Use of intravascular stents in the treatment of internal carotid and extracranial vertebral artery pseudoaneurysms. Am J Neuroradiol17(4): 693–696, 1996.
9.
ChiaradioJC: Intravascular graft stent treatment of a ruptured fusiform dissecting aneurysm of the intracranial vertebral artery: Technical case report. Neurosurgery50(1): 213–216; discussion 216–217, 2002.
10.
VanninenRManninenH and RonkainenA: Broad-based intracranial aneurysms: Thrombosis induced by stent placement. Am J Neuroradiol, 24(2): 263–266, 2003.
11.
ByunHSRheeK: Intraaneurysmal flow changes affected by clip location and occlusion magnitude in a lateral aneurysm model. Med Eng Phys25(7): 581–589, 2003.
12.
HanelRA: Advances in stent-assisted management of intracranial occlusive disease and cerebral aneurysms. Tech Vasc Interv Radiol7(4): 202–209, 2004.
13.
CantonGLevyDILasherasJC: Hemodynamic changes due to stent placement in bifurcating intracranial aneurysms. J Neurosurg103(1): 146–155, 2005.
14.
CantonG: Flow changes caused by the sequential placement of stents across the neck of sidewall cerebral aneurysms. J Neurosurg103(5): 891–902, 2005.
15.
MericleRA: Delayed aneurysm regrowth and recanalization after Guglielmi detachable coil treatment. Case report. J Neurosurg89(1): 142–145, 1998.
16.
TurjmanF: Combined stent implantation and endosaccular coil placement for treatment of experimental wide-necked aneurysms: A feasibility study in swine. Am J Neuroradiol15(6): 1087–1090, 1994.
17.
WakhlooAK: Self-expanding nitinol stents in canine vertebral arteries: Hemodynamics and tissue response. Am J Neuroradiol16(5): 1043–1051, 1995.
18.
RaymondJ: Healing mechanisms in experimental aneurysms. I. Vascular smooth muscle cells and neointima formation. J Neuroradiol26(1): 7–20, 1999.
19.
DesfaitsACRaymondJ and MuizelaarJP: Growth factors stimulate neointimal cells in vitro and increase the thickness of the neointima formed at the neck of porcine aneurysms treated by embolization. Stroke31(2): 498–507, 2000.
20.
RaymondJDesfaitsACRoyD: Fibrinogen and vascular smooth muscle cell grafts promote healing of experimental aneurysms treated by embolization. Stroke30(8): 1657–1664, 1999.
21.
ModaraiB: The role of neovascularisation in the resolution of venous thrombus. Thromb Haemost93(5): 801–809, 2005.
22.
OwensGKKumarMSWamhoffBR: Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol Rev84(3): 767–801, 2004.
23.
StrotherCMGravesVBRappeA: Aneurysm hemodynamics: An experimental study. Am J Neuroradiol13(4): P. 1089–1095, 1992.
ShoE: Arterial enlargement in response to high flow requires early expression of matrix metalloproteinases to degrade extracellular matrix. Exp Mol Pathol73(2): 142–153, 2002.
26.
NabelEG: Direct transfer of transforming growth factor beta 1 gene into arteries stimulates fibrocellular hyperplasia. Proc Natl Acad Sci U S A90(22): 10759–10763, 1993.
27.
O'BrienER: Beta ig-h3, a transforming growth factor-beta-inducible gene, is overexpressed in atherosclerotic and restenotic human vascular lesions. Arterioscler Thromb Vasc Biol16(4): 576–584, 1996.
28.
NanjoH: Intermittent short-duration exposure to low wall shear stress induces intimal thickening in arteries exposed to chronic high shear stress. Exp Mol Pathol80(1): 38–45, 2006.
29.
MondyJS: Platelet-derived growth factor ligand and receptor expression in response to altered blood flow in vivo. Circ Res81(3): 320–327, 1997.
30.
PalumboR: Different effects of high and low shear stress on platelet-derived growth factor isoform release by endothelial cells: Consequences for smooth muscle cell migration. Arterioscler Thromb Vasc Biol22(3): 405–411, 2002.
31.
MonraatsPS: Tumor necrosis factor-alpha plays an important role in restenosis development. Faseb J19(14): 1998–2004, 2005.
32.
RectenwaldJE: Direct evidence for cytokine involvement in neointimal hyperplasia. Circulation102(14): 1697–1702, 2000.
33.
MillerAM: TNF alpha increases the inflammatory response to vascular balloon injury without accelerating neointimal formation. Atherosclerosis179(1): 51–59, 2005.
34.
TreskaV: Inflammation in the wall of abdominal aortic aneurysm and its role in the symptomatology of aneurysm. Cytokines Cell Mol Ther7(3): 91–97, 2002.
35.
YoshizumiM: Stress and vascular responses: Atheroprotective effect of laminar fluid shear stress in endothelial cells: Possible role of mitogen-activated protein kinases. J Pharmacol Sci91(3): 172–176, 2003.
36.
HumphriesJ: Monocyte chemotactic protein-1 (MCP-1) accelerates the organization and resolution of venous thrombi. J Vasc Surg30(5): 894–899, 1999.
37.
GersztenRE: MCP-1 and IL-8 trigger firm adhesion of monocytes to vascular endothelium under flow conditions. Nature398(6729): 718–723, 1999.
38.
ShahPK: Inflammation, neointimal hyperplasia, and restenosis: As the leukocytes roll, the arteries thicken. Circulation107(17): 2175–2177, 2003.
39.
MelchionnaR: Laminar shear stress inhibits CX-CR4 expression on endothelial cells: Functional consequences for atherogenesis. Faseb J19(6): 629–631, 2005.
40.
ShyyYJ: Fluid shear stress induces a biphasic response of human monocyte chemotactic protein 1 gene expression in vascular endothelium. Proc Natl Acad Sci U S A91(11): 4678–4682, 1994.
41.
YongVW: Metalloproteinases in biology and pathology of the nervous system. Nat Rev Neurosci2(7): 502–511, 2001.
GalisZSKhatriJJ: Matrix metalloproteinases in vascular remodeling and atherogenesis: The good, the bad, and the ugly. Circ Res90(3): 251–262, 2002.
44.
BendeckMP: Smooth muscle cell migration and matrix metalloproteinase expression after arterial injury in the rat. Circ Res75(3): 539–545, 1994.
45.
SouthgateKM: Involvement of extracellular-matrix-degrading metalloproteinases in rabbit aortic smooth-muscle cell proliferation. Biochem J288 (Pt 1): 93–99, 1992.
46.
GalisZS: Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J Clin Invest94(6): 2493–2503, 1994.
47.
MagidRMurphyTJGalisZS: Expression of matrix metalloproteinase-9 in endothelial cells is differentially regulated by shear stress. Role of c-Myc. J Biol Chem278(35): 3294–3299, 2003.
48.
NikkariST: Smooth muscle cell expression of extracellular matrix genes after arterial injury. Am J Pathol144(6): 1348–1356, 1994.
49.
ZubilewiczT: Injury in vascular surgery — The intimal hyperplastic response. Med Sci Monit7(2): 316–324, 2001.
50.
MoldovanNI: Contribution of monocytes/macrophages to compensatory neovascularization: The drilling of metalloelastase-positive tunnels in ischemic myocardium. Circ Res87(5): 378–384, 2000.
