Browse > Article
http://dx.doi.org/10.3340/jkns.2019.0077

Vasa Vasorum Densities in Human Carotid Atherosclerosis Is Associated with Plaque Development and Vulnerability  

Joo, Sung-Pil (Department of Neurosurgery, Chonnam National University Hospital, Chonnam National University Medical School)
Lee, Seung-Won (Department of Neurosurgery, Chonnam National University Hospital, Chonnam National University Medical School)
Cho, Yong-Hwan (Department of Neurosurgery, Chonnam National University Hospital, Chonnam National University Medical School)
Kim, You-Sub (Department of Neurosurgery, Chonnam National University Hospital, Chonnam National University Medical School)
Seo, Bo-Ra (Department of Neurosurgery, Chonnam National University Hospital, Chonnam National University Medical School)
Kim, Hyung-Seok (Department of Forensic Medicine, Chonnam National University Hospital, Chonnam National University Medical School)
Kim, Tae-Sun (Department of Neurosurgery, Chonnam National University Hospital, Chonnam National University Medical School)
Publication Information
Journal of Korean Neurosurgical Society / v.63, no.2, 2020 , pp. 178-187 More about this Journal
Abstract
Objective : The extensive vasa vasorum network functions as a conduit for the entry of inflammatory cells or factors that promote the progression of angiogenesis and plaque formation. Therefore, we investigated the correlation between the carotid vasa vasorum activities and carotid plaque vulnerability using indocyanine green video angiography (ICG-VA) during carotid endarterectomy (CEA). Methods : Sixty-nine patients who underwent CEA were enrolled prospectively from September 2015 to December 2017. During CEA, a bolus of ICG was injected intravenously before and after resecting the atheroma. Additionally, we performed immunohistochemistry using CD68 (a surface marker of macrophages), CD117 (a surface marker of mast cells), and CD4 and CD8 (surface markers of T-cells) antibodies to analyze the resected plaque specimens. Results : The density of active vasa vasorum was observed in all patients using ICG-VA. The vasa vasorum externa (VVE) and interna (VVI) were seen in 11 (16%) and 57 patients (82.6%), respectively. Macroscopically, the VVE-type patterns were strongly associated with preoperative angiographic instability (81.8%, p=0.005) and carotid plaque vulnerability (90.9%, p=0.017). In contrast, the VVI-type patterns were weakly associated with angiographic instability (31.6%) and plaque vulnerability (49.1%). CD68-stained macrophages and CD117-stained mast cells were observed more frequently in unstable plaques than in stable plaques (p<0.0001, p=0.002, respectively). Conclusion : The early appearance of VVE, along with the presence of many microvessel channels that provided nutrients to the developing and expanding atheroma during ICG-VA, was strongly associated with unstable carotid plaques. The degree of infiltration of macrophages and mast cells is possibly related to the formation of unstable plaques.
Keywords
Atherosclerosis; Plaque, Atherosclerotic; Endarterectomy, Carotid; Indocyanine green; Vasa vasorum;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Boyle JJ : Association of coronary plaque rupture and atherosclerotic inflammation. J Pathol 181 : 93-99, 1997   DOI
2 Dashti R, Laakso A, Niemela M, Porras M, Hernesniemi J : Microscopeintegrated near-infrared indocyanine green videoangiography during surgery of intracranial aneurysms: the Helsinki experience. Surg Neurol 71 : 543-550; discussion 550, 2009   DOI
3 Doyle B, Caplice N : Plaque neovascularization and antiangiogenic therapy for atherosclerosis. J Am Coll Cardiol 49 : 2073-2080, 2007   DOI
4 Feinstein SB : Contrast ultrasound imaging of the carotid artery vasa vasorum and atherosclerotic plaque neovascularization. J Am Coll Cardiol 48 : 236-243, 2006   DOI
5 Fisher M, Paganini-Hill A, Martin A, Cosgrove M, Toole JF, Barnett HJ, et al. : Carotid plaque pathology: thrombosis, ulceration, and stroke pathogenesis. Stroke 36 : 253-257, 2005   DOI
6 Fleiner M, Kummer M, Mirlacher M, Sauter G, Cathomas G, Krapf R, et al. : Arterial neovascularization and inflammation in vulnerable patients: early and late signs of symptomatic atherosclerosis. Circulation 110 : 2843-2850, 2004   DOI
7 Gronholdt ML : Ultrasound and lipoproteins as predictors of lipid-rich, rupture-prone plaques in the carotid artery. Arterioscler Thromb Vasc Biol 19 : 2-13, 1999   DOI
8 Haga S, Nagata S, Uka A, Akagi Y, Hamada Y, Shono T : Near-infrared indocyanine green videoangiography for assessment of carotid endarterectomy. Acta Neurochir (Wien) 153 : 1641-1644; discussion 1644, 2011   DOI
9 Hansson GK, Libby P, Schonbeck U, Yan ZQ : Innate and adaptive immunity in the pathogenesis of atherosclerosis. Circ Res 91 : 281-291, 2002   DOI
10 Hiyama T, Tanaka T, Endo S, Komine K, Kudo T, Kobayashi H, et al. : Angiogenesis in atherosclerotic plaque obtained from carotid endarterectomy: association between symptomatology and plaque morphology. Neurol Med Chir (Tokyo) 50 : 1056-1061, 2010   DOI
11 Kamiyama K, Nakagawara J, Takada H, Fumoto K, Osato T, Nakamura H : Transformation of the vasa vasorum from normal vessel structures to atheroma nutrient vessels on ICG angiography of cervical carotid artery stenosis. Surg Cereb Stroke (Jpn) 39 : 413-419, 2011   DOI
12 Katano H, Yamada K, Sakurai K, Takahashi S : Depiction of the vasa vasorum during carotid endarterectomy by intraoperative videoangiography. J Stroke Cerebrovasc Dis 23 : 2920-2927, 2014   DOI
13 Kawahara I, Morikawa M, Honda M, Kitagawa N, Tsutsumi K, Nagata I, et al. : High-resolution magnetic resonance imaging using gadoliniumbased contrast agent for atherosclerotic carotid plaque. Surg Neurol 68 : 60-65; discussion 65-66, 2007   DOI
14 Kumamoto M, Nakashima Y, Sueishi K : Intimal neovascularization in human coronary atherosclerosis: its origin and pathophysiological significance. Hum Pathol 26 : 450-456, 1995   DOI
15 Lane B, Bohnstedt BN, Cohen-Gadol AA : A prospective comparative study of microscope-integrated intraoperative fluorescein and indocyanine videoangiography for clip ligation of complex cerebral aneurysms. J Neurosurg 122 : 618-626, 2015   DOI
16 Lee CH, Jung YS, Yang HJ, Son YJ, Lee SH : An innovative method for detecting surgical errors using indocyanine green angiography during carotid endarterectomy: a preliminary investigation. Acta Neurochir (Wien) 154 : 67-73; discussion 73, 2012   DOI
17 Lee RT, Libby P : The unstable atheroma. Arterioscler Thromb Vasc Biol 17 : 1859-1867, 1997   DOI
18 Libby P : Inflammation in atherosclerosis. Arterioscler Thromb Vasc Biol 32 : 2045-2051, 2012   DOI
19 Legein B, Temmerman L, Biessen EA, Lutgens E : Inflammation and immune system interactions in atherosclerosis. Cell Mol Life Sci 70 : 3847-3869, 2013   DOI
20 Li ZY, Howarth SP, Tang T, Gillard JH : How critical is fibrous cap thickness to carotid plaque stability? A flow-plaque interaction model. Stroke 37 : 1195-1199, 2006   DOI
21 Libby P : Inflammation in atherosclerosis. Nature 420 : 868-874, 2002   DOI
22 Libby P, Lichtman AH, Hansson GK : Immune effector mechanisms implicated in atherosclerosis: from mice to humans. Immunity 38 : 1092-1104, 2013   DOI
23 Mofidi R, Crotty TB, McCarthy P, Sheehan SJ, Mehigan D, Keaveny TV : Association between plaque instability, angiogenesis and symptomatic carotid occlusive disease. Br J Surg 88 : 945-950, 2001   DOI
24 Mono ML, Karameshev A, Slotboom J, Remonda L, Galimanis A, Jung S, et al. : Plaque characteristics of asymptomatic carotid stenosis and risk of stroke. Cerebrovasc Dis 34 : 343-350, 2012   DOI
25 Moon HS, Joo SP, Seo BR, Jang JW, Kim JH, Kim TS : Value of indocyanine green videoangiography in deciding the completeness of cerebrovascular surgery. J Korean Neurosurg Soc 53 : 349-355, 2013   DOI
26 Moreno PR, Purushothaman KR, Fuster V, Echeverri D, Truszczynska H, Sharma SK, et al. : Plaque neovascularization is increased in ruptured atherosclerotic lesions of human aorta: implications for plaque vulnerability. Circulation 110 : 2032-2038, 2004   DOI
27 Roessler K, Krawagna M, Dorfler A, Buchfelder M, Ganslandt O : Essentials in intraoperative indocyanine green videoangiography assessment for intracranial aneurysm surgery: conclusions from 295 consecutively clipped aneurysms and review of the literature. Neurosurg Focus 36 : E7, 2014
28 Moulton KS, Vakili K, Zurakowski D, Soliman M, Butterfield C, Sylvin E, et al. : Inhibition of plaque neovascularization reduces macrophage accumulation and progression of advanced atherosclerosis. Proc Natl Acad Sci U S A 100 : 4736-4741, 2003   DOI
29 North American Symptomatic Carotid Endarterectomy Trial Collaborators, Barnett HJM, Taylor DW, Haynes RB, Sackett DL, Peerless SJ, et al. : Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med 325 : 445-453, 1991   DOI
30 Ritman EL, Lerman A : The dynamic vasa vasorum. Cardiovasc Res 75 : 649-658, 2007   DOI
31 Ross R : Atherosclerosis--an inflammatory disease. N Engl J Med 340 : 115-126, 1999   DOI
32 Schoenenberger F, Mueller A : On the vascularization of the bovine aortic wall. Helv Physiol Pharmacol Acta 18 : 136-150, 1960
33 Shah F, Balan P, Weinberg M, Reddy V, Neems R, Feinstein M, et al. : Contrast-enhanced ultrasound imaging of atherosclerotic carotid plaque neovascularization: a new surrogate marker of atherosclerosis? Vasc Med 12 : 291-297, 2007   DOI
34 Staub D, Schinkel AF, Coll B, Coli S, van der Steen AF, Reed JD, et al. : Contrast-enhanced ultrasound imaging of the vasa vasorum: from early atherosclerosis to the identification of unstable plaques. JACC Cardiovasc Imaging 3 : 761-771, 2010   DOI
35 Weber C, Noels H : Atherosclerosis: current pathogenesis and therapeutic options. Nat Med 17 : 1410-1422, 2011   DOI
36 Zhang Y, Cliff WJ, Schoefl GI, Higgins G : Immunohistochemical study of intimal microvessels in coronary atherosclerosis. Am J Pathol 143 : 164-172, 1993
37 Willems S, Vink A, Bot I, Quax PH, de Borst GJ, de Vries JP, et al. : Mast cells in human carotid atherosclerotic plaques are associated with intraplaque microvessel density and the occurrence of future cardiovascular events. Eur Heart J 34 : 3699-3706, 2013
38 Yamada K, Yoshimura S, Kawasaki M, Enomoto Y, Asano T, Hara A, et al. : Embolic complications after carotid artery stenting or carotid endarterectomy are associated with tissue characteristics of carotid plaques evaluated by magnetic resonance imaging. Atherosclerosis 215 : 399-404, 2011   DOI
39 Yoshida K, Narumi O, Chin M, Inoue K, Tabuchi T, Oda K, et al. : Characterization of carotid atherosclerosis and detection of soft plaque with use of black-blood MR imaging. AJNR Am J Neuroradiol 29 : 868-874, 2008   DOI
40 Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. JAMA 273 : 1421-1428, 1995   DOI
41 Alonso A, Artemis D, Hennerici MG : Molecular imaging of carotid plaque vulnerability. Cerebrovasc Dis 39 : 5-12, 2015   DOI