Significance of cyclooxygenase-2 elevation in middle cerebral artery for patients with hemorrhagic moyamoya disease

Abstract

The etiology and pathogenesis of moyamoya disease (MMD) remain elusive. Some inflammatory proteins, such as cyclooxygenase (COX)-2, are believed to be implicated in the development of MMD. So far, the relationship between COX-2 and MMD is poorly understood and reports on the intracranial vessels of MMD patients are scanty. In this study, tiny pieces of middle cerebral artery (MCA) and superficial temporal artery (STA) from 13 MMD patients were surgically harvested. The MCA and STA samples from 5 control patients were also collected by using the same technique. The expression of COX-2 was immunohistochemically detected and the average absorbance (A) of positively-stained areas was measured. High-level COX-2 expression was found in all layers of the MCA samples from all 5 hemorrhagic MMD patients, while positive but weak expression of COX-2 was observed only in the endothelial layer of the MCA samples from most ischemic MMD patients (6/8, 75%). The average A values of COX-2 in the hemorrhagic MMD patients were substantially higher than those in their ischemic counterparts (t=4.632, P=0.001). There was no significant difference in the COX-2 expression among the “gender” groups, or “radiographic grade” groups, or “lesion location” groups (P>0.05 for all). The COX-2 expression was detected neither in the MCA samples from the controls nor in all STA specimens. Our results suggested that COX-2 was up-regulated in the MCA of MMD patients, especially in hemorrhagic MMD patients. We are led to speculate that COX-2 may be involved in the pathogenesis of MMD and even contribute to the hemorrhagic stroke of MMD patients.

Keywords

moyamoya disease / middle cerebral artery / COX-2 / inflammation / hemorrhage

References

[1] SuzukiJ, KodamaN. Moyamoya disease—a review. Stroke, 1983, 14(1): 104-109 PMID: 6823678

[2] NishimotoA, TakeuchiS. Abnormal cerebrovascular network related to the internal cartoid arteries. J Neurosurg, 1968, 29(3): 255-260 PMID: 5684407

[3] SonobeS, FujimuraM, NiizumaK, et al. . Temporal profile of the vascular anatomy evaluated by 9.4-T magnetic resonance angiography and histopathological analysis in mice lacking RNF213: a susceptibility gene for moyamoya disease. Brain Res, 2014, 1552: 64-71 PMID: 24440776

[4] KurodaS, HoukinK. Moyamoya disease: current concepts and future perspectives. Lancet Neurol, 2008, 7(11): 1056-1066 PMID: 18940695

[5] YoungAM, KarriSK, OgilvyCS, et al. . Is there a role for treating inflammation in moyamoya disease?: a review of histopathology, genetics, and signaling cascades. Front Neurol, 2013, 4: 105 PMID: 23966972 PMCID: 3742998

[6] TakagiY, KikutaK, NozakiK, et al. . Expression of hypoxia-inducing factor-1 alpha and endoglin in intimal hyperplasia of the middle cerebral artery of patients with Moyamoya disease. Neurosurgery, 2007, 60(2): 338-345 PMID: 17290185

[7] YamamotoM, AoyagiM, FukaiN, et al. . Increase in prostaglandin E(2) production by interleukin-1beta in arterial smooth muscle cells derived from patients with moyamoya disease. Circ Res, 1999, 85(10): 912-918 PMID: 10559138

[8] SmithER, ScottRM. Moyamoya: epidemiology, presentation, and diagnosis. Neurosurg Clin N Am, 2010, 21(3): 543-551 PMID: 20561502

[9] MasudaJ, OgataJ, YutaniC. Smooth muscle cell proliferation and localization of macrophages and T cells in the occlusive intracranial major arteries in moyamoya disease. Stroke, 1993, 24(12): 1960-1967 PMID: 7902623

[10] SakamotoS, KiuraY, YamasakiF, et al. . Expression of vascular endothelial growth factor in dura mater of patients with moyamoya disease. Neurosurg Rev, 2008, 31(1): 77-81 PMID: 17912564

[11] FurunoA, WatariK, NakamuraM, et al. . A natural anti-inflammatory enone fatty acid inhibits angiogenesis by attenuating nuclear factor-kappaB signaling in vascular endothelial cells. Int J Oncol, 2011, 38(2): 493-501 PMID: 21132269

[12] HojoM, HoshimaruM, MiyamotoS, et al. . Role of transforming growth factor-beta1 in the pathogenesis of moyamoya disease. J Neurosurg, 1998, 89(4): 623-629 PMID: 9761057

[13] KangHS, KimJH, PhiJH, et al. . Plasma matrix metalloproteinases, cytokines and angiogenic factors in moyamoya disease. J Neurol Neurosurg Psychiatry, 2010, 81(6): 673-678 PMID: 19965844

[14] JeonJS, AhnJH, MoonYJ, et al. . Expression of cellular retinoic acid-binding protein-I (CRABP-I) in the cerebrospinal fluid of adult onset moyamoya disease and its association with clinical presentation and postoperative haemodynamic change. J Neurol Neurosurg Psychiatry, 2014, 85(7): 726-731 PMID: 24292994

[15] BabaT, HoukinK, KurodaS. Novel epidemiological features of moyamoya disease. J Neurol Neurosurg Psychiatry, 2008, 79(8): 900-904 PMID: 18077479

[16] CzabankaM, Pena-TapiaP, SchubertGA, et al. . Proposal for a new grading of Moyamoya disease in adult patients. Cerebrovasc Dis, 2011, 32(1): 41-50 PMID: 21576942

[17] WakaiK, TamakoshiA, IkezakiK, et al. . Epidemiological features of moyamoya disease in Japan: findings from a nationwide survey. Clin Neurol Neurosurg, 1997, 99: S1-S5 PMID: 9409395

[18] IkedaH, SasakiT, YoshimotoT, et al. . Mapping of a familial moyamoya disease gene to chromosome 3p24.2-p26. Am J Hum Genet, 1999, 64(2): 533-537 PMID: 9973290 PMCID: 1377762

[19] RimarachinJA, JacobsonJA, SzaboP, et al. . Regulation of cyclooxygenase-2 expression in aortic smooth muscle cells. Arterioscler Thromb, 1994, 14(7): 1021-1031 PMID: 8018656

[20] LiJ, ChenX, DongX, et al. . Specific COX-2 inhibitor, meloxicam, suppresses proliferation and induces apoptosis in human HepG2 hepatocellular carcinoma cells. J Gastroenterol Hepatol, 2006, 21(12): 1814-1820 PMID: 17074019