Cardiovascular disease is an important public health issue and a major cause of death worldwide.1 Cardiovascular disease is not a single disease, however; it is a broad term used to describe a complex class of disease. The challenges involved in identifying a suitable biomarker stem largely from the diversity of the disease itself.
Oxidative post-translational modifications (OPTMs) are caused by reactions between protein amino acid residues and reactive oxygen or reactive nitrogen species — highly reactive molecules arising from incomplete chemical reactions. Studies have shown that OPTMs contribute to cardiovascular disease; however, emerging evidence indicates that OPTMs may also have a positive role to play in cell function due to their involvement in the regulation of cell growth.2
To date, we have seen only the tip of the iceberg in terms of the role of OPTMs in cardiovascular disease. The downstream consequences of OPTMs and their functional significance as biomarkers of cardiovascular disease are poorly understood.
Traditional biomarkers of cardiac injury, such as troponin I and T, have been useful in identifying patients at the time of injury because they are released as an immediate response. These traditional biomarkers are not effective, however, when looking for degenerative disease factors as a result of long-term oxidative damage.
Both redox and oxidative stress proteomes appear to be related to the changes in the disease modification process in the case of heart attack, hypertension and inflammation, but functionally, a knowledge gap exists. By and large, these proteomes have been evaluated indirectly, by association. Improving recognition of OPTMs is the only way to definitively identify a reliable set of cardiovascular disease biomarkers.
Kumar et al. (2012) reviewed the use of OPTMs as biomarkers and predictors of disease. The challenges most noted were limitations imposed in analytic detection.3
As the field matures, our ability to bypass challenges surrounding methodology, instrumentation and complexity is improving. Currently, a typical mass spectrometry analysis contains many unidentified peptides and cannot operate without a specific strategy. However, recent advances in instrumentation — such as the new Q Executive (Thermo Scientific) and high-throughput instruments with both ESI and MALDI ionization capabilities — are increasing accessibility within the scientific community.
A promising road lies ahead in biomarker discovery, as technology continues to keep up with the demands of researchers. As techniques become increasingly robust, significant clinical gains will be made in the diagnosis and prevention of cardiovascular disease.
2. Yan, L.J., Christians, E.S., Liu, L., Xiao, X., Sohal, R.S., and Benjamin, I.J. (2002) “Mouse heat shock transcription factor 1 deficiency alters cardiac redox homeostasis and increases mitochondrial oxidative damage,” EMBO, 21 (pp. 5164–72).
3. Kumar, V., Calamaras, T.D., Haeussler, D., Colucci, W.S., Cohen, R.A., McComb, M.E., Pimentel, D., and Bachschmid, M.M. (2012) “Cardiovascular Redox and Ox Stress Proteomics,” Antioxidants and Redox Signalling, 17(11) (pp.1528–59).
Post Author: Miriam Pollak.