Cardiovascular proteomics: past, present, and future

Abstract

With cardiovascular (CV)-related disorders accounting for the highest mortality rates in the world, affecting the quantity and quality of life of patients and creating an economic burden of prolonged therapeutic intervention, there is great significance in understanding the cellular and molecular alterations that influence the progression of these pathologies. The cellular genotype is regulated by the DNA component, whilst the cellular phenotype is influenced by the protein complement. By improving the understanding of the molecular mechanisms that influence the protein profile, the pathologies that influence the intrinsic functions of the CV system may be detected earlier or managed more efficiently. This is achievable with technologies encompassed by 'proteomics.' Proteomic investigations of CV diseases, including dilated cardiomyopathy (DCM), atherosclerosis, and ischemia/reperfusion (I/R) injury, have identified candidate proteins altered with the pathologic states, complementing past biochemical and physiologic observations. Whilst proteomics is still a relatively new discipline to be applied to the basic scientific investigation of CV diseases, it is emerging as a technique to screen for potential biomarkers in both tissues/cells and biologic fluids (biofluids), as well as to identify the targets of existing therapeutics. By enabling the separation of complex mixtures over numerous dimensions, exploiting the intrinsic properties of proteins, including charge state, molecular mass, and hydrophobicity, in addition to cellular location, the discrete alterations within the cell may be resolved. Proteomics has shown alterations to myofilament proteins including troponin I and myosin light chain, correlating with the reduction in contractility in the myocardium from DCM and I/R. The diverse cell types that coalesce to induce atherosclerotic plaque formation have been investigated both collectively and individually to elucidate the influence of the modifications to single cell types on the developing plaque as a whole. Proteomics has also been used to observe changes to biofluids occurring with these pathologies, a new potential link between basic science and clinical applications. The development of CV proteomics has helped to identify a number of possible protein candidates, and offers the potential to treat and diagnose CV disease more effectively in the future.