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Increased expression of phosphorylated forms of heat‐shock protein‐27 and p38 MAPK in macrophage‐rich regions of fibro‐fatty atherosclerotic lesions in the rabbit
Author(s) -
Shafi Shahida,
Codrington Rosalind,
Gidden Lewis Michael,
Ferns Gordon Ashley Anthony
Publication year - 2016
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/iep.12167
Subject(s) - immunostaining , hsp27 , western blot , p38 mitogen activated protein kinases , immunohistochemistry , medicine , endocrinology , macrophage , heat shock protein , apolipoprotein b , blot , mapk/erk pathway , chemistry , cholesterol , biology , hsp70 , phosphorylation , biochemistry , in vitro , gene
Summary We aimed to assess the expression and distribution of Hsp27, pH sp27 (Ser82), p38 MAPK and p‐p38 MAPK in fibro‐fatty atherosclerotic lesions and the myocardium of hypercholesterolaemic rabbits. Male New Zealand white rabbits were fed a high‐cholesterol diet for 18 weeks, maintaining serum cholesterol at approximately 20 mmol/l over this period. Aortic arch and myocardial tissues were analysed by Western blot, immunohistochemistry and double immunofluorescence. Plasma Hsp27 levels were measured by ELISA . There was a significant increase in the expression of monomeric and dimeric forms of Hsp27, together with pH sp27 (Ser82), p38 MAPK and p‐p38 MAPK in the fibro‐fatty atherosclerotic lesions ( P < 0.01; P < 0.05; P < 0.001; and P < 0.001, respectively) and the myocardial tissues ( P < 0.001) from the cholesterol‐fed rabbits compared with equivalent tissues from controls when the plasma concentration was low. Immunohistochemical analysis of the fibro‐fatty lesions showed marked increases in Hsp27 and pH sp27 (Ser82) immunoreactivity. Double immunostaining showed intense expression of pH sp27 and p‐p38 MAPK in regions that were rich in macrophages, suggesting a close association with these inflammatory cells, whereas, in regions rich in smooth muscle cells, only p‐p38 MAPK was found to be strongly expressed. An increased expression of pH sp27 (Ser82) was spatially associated with increased p‐p38 MAPK within fibro‐fatty atherosclerotic lesions and was colocalized to regions rich in macrophages. The initial increase in plasma Hsp27 levels may reflect the increase in systemic inflammation and oxidative stress in the early phases of disease. The falling concentrations subsequently may be coincident with the development of the advanced atherosclerotic lesions.