title: Increased expression of phosphorylated forms of heat-shock protein-27 and p38MAPK in macrophage-rich regions of fibro-fatty atherosclerotic lesions in the rabbit.
abstract: We aimed to assess the expression and distribution of Hsp27, pHsp27 (Ser82), p38MAPK and p-p38MAPK 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 pHsp27 (Ser82), p38MAPK and p-p38MAPK 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 pHsp27 (Ser82) immunoreactivity. Double immunostaining showed intense expression of pHsp27 and p-p38MAPK 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-p38MAPK was found to be strongly expressed. An increased expression of pHsp27 (Ser82) was spatially associated with increased p-p38MAPK 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.
authors: Faculty of Health and Medical Sciences, Department of Biochemistry and Physiology, University of Surrey, Guildford, Surrey, UK.
authors: Shahida
authors: S
authors: Shafi
authors: Babraham Research Campus, ABeterno Ltd, Cambridge, UK.
authors: Rosalind
authors: R
authors: Codrington
authors: Faculty of Health and Medical Sciences, Department of Biochemistry and Physiology, University of Surrey, Guildford, Surrey, UK.
authors: Lewis Michael
authors: LM
authors: Gidden
authors: Division of Medical Education, Brighton and Sussex Medical School, University of Brighton, Brighton, UK.
authors: Gordon Ashley Anthony
authors: GA
authors: Ferns
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000139:chemically induced / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D004195:Disease Models, Animal; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D010766:Phosphorylation; D011817:Rabbits; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D055551:HSP27 Heat-Shock Proteins; D002784:Cholesterol; D048051:p38 Mitogen-Activated Protein Kinases
keywords: atherosclerosis; macrophages; phosphorylated Hsp27 (Ser82) and p38MAPK; plaques