Carbonic Anhydrase IX – Hypoxia Marker in the Aortic Wall
Yury Sheykin, Seymour Rosen. Beth Israel Deaconess Medical Center, Boston, MA; Harvard Medical School, Boston, MA
Background: Carbonic anhydrases (CA) catalyze conversion of CO2 and H2O to HCO3- and H+. CA IX is particularly interesting because of its over expression in human cancers, likely to protect the tumor from acidotic environment engendered by anaerobic metabolism. Its expression is triggered by hypoxia-inducible factor-1 alpha, the master regulator of cellular response to hypoxia. Anti-CA IX antibody is clinically available for diagnostic imaging and potential cancer immunoradiotherapy.
Hypoxia in the vascular wall is one of the factors contributing to development of atherosclerosis and aortic aneurysms. Large arteries are particularly susceptible to hypoxia by nature of their blood supply. Luminal diffusion and adventitial vasa vasorum provide adequate vascular wall oxygenation in a healthy vessel, but fail to do so in various pathologic states. Indeed, frank aortic infarction is commonly seen in dissecting aortic aneurysms, following rather than preceding the latter (Circulation 1978;58:876-81).
Design: Using immunohistochemistry, we investigated expression of CA IX in aortic specimens obtained from patients with non-dissecting aortic aneurysms (n=13), dissecting aortic aneurysms (n=6) and granulomatous vasculitis (n=4). These were non-selected vascular surgical specimens received by our department within an 8-month period.
Results: In non-dissecting aneurysms, staining was frequently found in smooth muscle cells in the central media. In dissecting aneurysms, smooth muscle cells surrounding the areas of dissection were positive for CA IX. Vasculitis specimens exhibited strong CA IX staining within inflammatory foci and the surrounding smooth muscle cells. Staining was also seen in smooth muscle cells underlying atherosclerotic plaques and within the infarcted zones (CA IX is relatively resistant to proteolytic degradation). A further confirmation that CA IX staining truly indicates hypoxia was that prostate, testis and kidney infarcts (n=5) showed intense staining in zones bordering infarcted areas in which hypoxia would be anticipated.
Conclusions: These findings show that CA IX is consistently expressed in the diseased aortic wall and likely reflects hypoxic injury. CA IX up-regulation in the vascular wall is likely an adaptive mechanism aimed at preservation of tissue viability during hypoxic stress. A potential exists for in vivo assessment of CA IX expression in aortic wall for identification of past or on-going hypoxia.
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 46, Wednesday Afternoon