HSPA12B and repairing the heart: beauty in simplicity

Abstract

This editorial refers to ‘HSPA12B attenuates cardiac dysfunction and remodelling after myocardial infarction through an eNOS-dependent mechanism’ by J. Li et al ., pp. 671–681, this issue. HSPA12B is a member of a newly identified subfamily of the Hsp70 family of heat shock proteins and is predominately expressed in endothelial cells.1,2 Blood pressure may play a role in its expression, as HSPA12B is expressed in endothelial cells in heart, adipose tissue, brain, kidney, and lung, but not in liver sinusoidal endothelial cells.1 In the heart and brain, vessels of all sizes express HSPA12B, whereas in lung and adipose tissue, expression is largely in capillaries. The cell-restricted expression of HSPA12B, which is otherwise not a feature of heat shock proteins, alone presages its importance to endothelial cell function and indeed studies have established that HSPA12B is required for angiogenesis, specifically in the processes of adhesion, migration, and tube formation.1,2 Endothelial cell HSPA12B expression seems to be dynamic and is increased in confluent HUVEC cultures kept in medium containing endothelial cell-specific growth factors, by heat shock, and during tubule formation.1–3 Protein levels are likely regulated by a post-transcriptional mechanism as well.1 Twenty-two putative client proteins have been identified for HSPA12B, including AKAP12 (A-kinase-anchoring protein 12) and hPODXL (human podocalyxin-like), both of which are implicated in cell adhesion, and aryl hydrocarbon receptor nuclear translocator (ARNT).1 HSPA12B also has protective actions in endothelial cells. Transgenic mice overexpressing the human hspa12b gene (including the endothelial cell-specific promoter) were found to be remarkably protected …