Stressing the obvious? Cell stress and cell stress proteins in cardiovascular disease

It is only some forty years since the discovery of the heat shock or cell stress response and just over twenty years since the heat shock/cell stress response was linked to protein misfolding. The plethora of intracellular proteins which promote correct protein folding in the cell, variously termed molecular chaperones, heat shock proteins, or cell stress proteins, have only been identified in the last fifteen years. During this period it has also been discovered that: (i) molecular chaperones are potent immunogens with immunomodulatory activity and (ii) they can be secreted by cells and exhibit intercellular signaling actions. These various functions of molecular chaperones are increasingly being linked to the pathology of the cardiovascular system. Molecular chaperones within cells can exhibit cardioprotection if their levels are artificially elevated, suggesting that these proteins may have therapeutic activity. In contrast, there is evidence that atherogenesis may be linked to immunity to one specific molecular chaperone, Hsp60. This may offer the possibility of treating atherosclerosis by vaccination. However, there is also growing evidence that secreted molecular chaperones have pro- or anti-inflammatory actions that are relevant to cardiovascular pathology. This review brings these various strands of research together to provide an overview of the role of molecular chaperones in cardiovascular disease.