Peptidyl-prolyl isomerases: functionality and potential therapeutic targets in cardiovascular disease

Peptidyl-prolyl cis/trans isomerases (PPIases) are a conserved group of enzymes that catalyse the conversion between cis and trans conformations of proline imidic peptide bonds. These enzymes play critical roles in regulatory mechanisms of cellular function and pathophysiology of disease. There are three different classes of PPIases and increasing interest in the development of specific PPIase inhibitors. Cyclosporin A, FK506, rapamycin and juglone are known PPIase inhibitors. In this article, we review recent advances in elucidating the role and regulation of the PPIase family in vascular disease. We will focus on Pin1, an important member of the PPIase family that plays a role in cell cycle progression, gene expression, as well as cell signalling and cell proliferation. Pin1 may be involved in atherosclerosis. The unique role of Pin1 as a molecular switch that impacts on multiple downstream pathways necessitates the evaluation of a highly specific Pin1 inhibitor to aid in a potential therapeutic drug discovery.