Abstract T MP120: Bone Morphogenic Protein Expression in Pericytes Is a Pathological Correlate of Vascular Cognitive Impairment
Introduction: Signaling abnormalities in transforming growth factor beta 1 (TGFβ1) are thought to play a detrimental role in pathogenesis of stroke and CARASIL, a hereditary type of vascular cognitive impairment (VCI). The largest group of TGFβ superfamily members, bone morphogenic proteins (BMPs), is known to contribute to pro-atherogenic phenotypic alterations in blood vessels or to play a detrimental role in neonatal hypoxia-ischemia. However, a comprehensive pathological analysis of BMPs in VCI and its comparison with Alzheimer’s disease (AD) has not been conducted.
Hypothesis: We assessed the hypothesis that BMPs play a crucial role in pathogenesis of VCI.
Methods: We evaluated post-mortem frontal lobe tissue from 7 VCI (mean ± SD, 80.9 ± 6.0 years old; brain weight, 1101 ± 89.9 g), 6 AD (81 ± 8.0 years old; 1056 ± 67.7 g), and 6 age-matched disease controls (73.8 ± 4.5 years old; 1190 ± 113.7 g). Brain sections were immunostained for TGFβ1 and brain-expressed BMPs (BMP-2, BMP-4, BMP-6, BMP-7, and BMP-9), and platelet derived growth factor receptor β (PDGFRβ) and α smooth muscle actin (αSMA) as pericyte markers. Besides, images of sections stained with conventional luxol fast blue were analyzed to estimate myelin attenuation by optical density.
Results: The expression of BMP-2 and BMP-4 was significantly upregulated in VCI compared to AD and/or disease controls specifically in the white matter but not in the cerebral cortex. BMP-2 and BMP-4 was found on the abluminal surface of capillaries and preferentially colocalized with PDGFRβ than αSMA, suggesting their expression in relatively immature pericytes. Myelin density was most reduced in VCI compared to AD or disease controls, and the degree of myelin loss was significantly correlated with greater expression of BMP-2/4 in the white matter when all the 19 cases were combined.
Conclusions: Our findings suggest that myelin loss evolves in parallel with BMP-2/4 upregulation in PDGFRβ-positive immature pericytes, with the highest upregulation in VCI. The increased BMP-2/4 expression may be a good pathological correlate of ischemic white matter damage associated with VCI.
Author Disclosures: M. Uemura: None. M. Ihara: None. K. Nagatsuka: None. A. Kinoshita: None. R. Takahashi: None.
- © 2014 by American Heart Association, Inc.