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Granzyme B is important in the progression of atherosclerosis
Author(s) -
Cruz Rani Priya,
Boivin Wendy,
Zhao Hongyan,
Choy Jonathan C,
McManus Bruce M,
Granville David J
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.174.9
Subject(s) - elastin , granzyme b , inflammation , apolipoprotein e , gamma ray burst , immune system , pathology , medicine , chemistry , immunology , t cell , disease , physics , astronomy
Granzyme B (GrB) is a serine protease expressed in certain T‐cells, NK cells, mast cells and macrophages. We have shown GrB expression in human atherosclerotic plaques and its levels correspond to disease severity. Hypothesis: During chronic hyperlipidemia and inflammation, GrB contributes to elastin degradation, medial thinning and reduced elasticity. Methods: To study the role of GrB in a chronic inflammatory, hyperlipidemic environment, ApoE−/− x GrB−/− double knockout (ApoE/GrB‐DKO) mice were created, fed a high fat diet for 30 wks and sacrificed. Tissues were stained with H&E, ORO and Movat's pentachrome. GrB co‐localization to elastin was assessed using confocal microscopy. Results: ApoE−/− mice developed xanthomatosis and atherosclerotic lesions by 30 weeks. The absence of the GrB gene in the ApoE/GrB‐DKO mice abolished cutaneous xanthomatosis in addition to both the frequency and size of atherosclerotic lesions. The absence of GrB was associated with a marked reduction of elastin degradation in both the skin and blood vessels. Using confocal microscopy, we observed GrB strongly co‐localized to the shoulder regions of plaques in addition to the medial elastin fibres. Conclusion: GrB plays a key role in atherosclerotic plaque formation. Lipid accumulation on elastin fibres promotes the recruitment of GrB resulting in a slow, chronic degradation of elastin.