The role of post-translational modifications in acute and chronic cardiovascular disease.

Research paper by Lauren E LE Smith, Melanie Y MY White

Indexed on: 26 Jun '14Published on: 26 Jun '14Published in: PROTEOMICS - Clinical Applications


Cardiovascular disease (CVD) in one of the leading causes of mortality and morbidity worldwide, accounting for both primary diseases of the heart and vasculature and arising as a co-morbidity with numerous pathologies, including type 2 diabetes mellitus (T2DM). There has been significant emphasis on the role of the genome in CVD, aiding in the definition of 'at-risk' patients. The extent of disease penetrance however, can be influenced by environmental factors that are not detectable by investigating the genome alone. By targeting the transcriptome in response to CVD, the interplay between genome and environment is more apparent, however this implies the level of protein expression without reference to proteolytic turnover, or potentially more importantly, without defining the role of PTMs in the development of disease. Here, we discuss the role of both brief and irreversible PTMs in the setting of myocardial ischemia/reperfusion injury. Key proteins involved in calcium regulation have been observed as differentially modified by phosphorylation/O-GlcNAcylation or phosphorylation/redox modifications, with the level of interplay dependent on the physiological or pathophysiological state. The ability to modify crucial sites to produce the desired functional output is modulated by the presence of other PTMs as exemplified in the T2DM heart, where hyperglycemia results in aberrant O-GlcNAcylation and advanced glycation end products. By using the signalling events predicted to be critical to post-conditioning, an intervention with great promise for the cardioprotection of the ischemia/reperfusion injured heart, as an example, we discuss the level of PTMs and their interplay. The inability of post-conditioning to protect the diabetic heart may be regulated by aberrant PTMs influencing those sites necessary for protection.