Heat shock protein 27: its potential role in vascular disease

Abstract

Heat shock proteins are molecular chaperones that have an ability to protect proteins from damage induced by environmental factors such as free radicals, heat, ischaemia and toxins, allowing denatured proteins to adopt their native configuration. Heat shock protein-27 (Hsp27) is a member of the small Hsp (sHsp) family of proteins, and has a molecular weight of approximately 27 KDa. In addition to its role as a chaperone, it has also been reported to have many additional functions. These include effects on the apoptotic pathway, cell movement and embryogenesis. In this review, we have focused on its possible role in vascular disease.

Figure 1

Monomeric Hsp27 acts as a capping protein for actin, limiting filament growth. It is phosphorylated by several mechanisms, and the phosphorylated dimer is the active molecule in chaperone activity, being involved in the renaturation of damaged proteins, and in targeting denatured proteins to the proteasome. Dimers may also be generated by the phosphorylation of Hsp27 oligomers.

Figure 2

Effects of heat shock on apoptosis related pathways. Heat shock stimulates apopotosis via several pathways. It also induces Hsp27 expression, and its phosphorylation. Hsp27 in turn acts to offset the potential damage induced by heat shock in part through inhibition of apoptosis. It does so at several steps in the apoptotic pathway.

Figure 3

Possible involvement of Hsp27 in atherogenesis. 1, Hsp27 is expressed by endothelial cells and may stimulate an autoimmune response; 2, Hsp27 is phosphorylated in platelets following treatment with aggregating agents, and may be involved in fibrin clot stabilization; 3, Hsp27 inhibits cell apoptosis; 4, Hsp27 helps maintain endothelial cell barrier function, this would tend to reduce the influx of plasma proteins such as LDL that may be involved in atherogenesis; 5, Hsp27 stabilises the actin cytoskeleton, and regulates actin microfilament dynamics and polymerization, and hence cell migration; 6, Hsp27 affects the expression of IL-10 by monocyte macrophages, and is thought to be anti-inflammatory; 7, Hsp inhibits monocyte/macrophage-mediated cell injury.