Abstract 3685: Collagen Isoform Distribution Patterns In Cerebral Vessels In CADASIL
Objective: Arteries in CADASIL are susceptible to fibrosis and smooth muscle cell loss. The molecular components underlying vascular remodeling are not well characterized. The purpose of this study was to test the hypothesis that distinct collagen isoforms accumulation in the media of the cerebral vessels in CADASIL.
Methods: Brain sections from six CADASIL patients with mutations in NOTCH3 were compared to age matched controls. Expression of Type I, II, III, IV, V, VI, and IX collagen were studied by immunohistochemistry.
Results: We identified a consistent increase of Type I, III, IV, and VI collagen content in the large and small vessels of CADASIL brains relative to controls. We did not find Type II, V, IX collagen in the brain. Within leptomeningeal arteries where we could definitively visualize the three layers of each vessel, we found that Type I, III, IV and VI collagens were found in heterogeneous locations. Types I and III collagen was mostly transmural or adventitial/medial. Type IV was strictly intimal/medial. Type VI was largely adventitial/medial. The most significant difference between CADASIL and controls was the appearance of all four collagen types in the vascular media. Within the thickened penetrating arteries of CADASIL patients, all four collagens extended through most of the arterial wall. Finally, we observed increased staining of capillaries in CADASIL for Type I, IV, and VI.
Conclusion: In CADASIL, brain vascular collagen subtypes are increased in multiple layers of both large and small vessels, with the most dramatic changes in the tunica media and thickened small penetrating vessels. These studies suggest that collagen accumulation in the vascular media may play a pathogenic role in small vessel disease.
- © 2012 by American Heart Association, Inc.