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FIT Insights

The Omics:

An Enlightening Frontier on the Horizon

Optimization of preventive measures to curtail cardiovascular diseases (CVD) has been a long-term goal of the scientific and clinical community. Although we have come a long way over the past three decades, novel and more precise ways to identify individuals at high risk for CVD events are being continuously being researched and calibrated. Biological markers, or biomarkers, have important implications for CVD risk prediction, stratification, diagnosis, and prognosis. The recent issue of Circulation Research Cardiovascular Omics Compendium highlights the existing frameworks to identify molecular level and population data on atherosclerosis and identified areas for potential improvement.

Among the major challenges in developing CVD biomarkers is the complexity of the disease process. The omics tools (including genomics, transcriptomics, proteomics, and metabolomics) are an exciting new methodology to aid the path of discovery.

The development of microarrays, proteomics, and nanotechnology – combined with data from the Human Genome Project and HapMap Project – are revolutionizing the pathways for discovering and investigating CVD biomarkers. The ability to simultaneously study a large number of proteins in the plasma, the plasma proteome, is a new opportunity to recognize fresh pathways and biomarkers for detecting CVD risk and facilitating diagnosis.

The human plasma proteome is a mixture of proteins derived from all tissues and representing a variety of metabolic pathways. The plasma proteome includes:

  • carrier proteins
  • immune system effectors (e.g., immunoglobulins and complement factors), tissue messengers (e.g., natriuretic peptides and interleukins)
  • products of tissue damage (e.g., troponin and creatine kinase)
  • other proteins involved in CVD.

The heterogeneous structure of the plasma proteome and its large range in protein concentrations have been a barrier to perform a complete simultaneous profiling of large numbers of plasma proteins. Affinity reagents, such as modified nucleic acid aptamers, have been described as another alternative to address the limitations of immunoassays. Oligonucleotide-based aptamers interact with protein surfaces by their folding capability and have a high-binding affinity. Recently chemically modified aptamers with improved affinity were developed via a commercial platform (SomaLogic, Inc, Boulder, Colo.).

Genomic medicine relies on the concept that an individual’s genomic makeup may be used to derive precision therapy and care. Implementation of this idea may have seemed far-fetched in the past but decreasing costs of genotyping and sequencing have made it an attractive prospect. Some challenges remain, including the need for proven information technology infrastructure, database buildup, methods for potential sharing for precise analysis approaches, and a dearth of medical and economic outcomes.

Pharmacogenetics has recently made waves in the faster pathway from discovery to clinical practice. The relatively rapid evolution of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors from genomics to clinical practice is one of the most promising recent advances in the application of pharmacogenetics to patient care. Although we are moving closer to the vision for enhanced use of pharmocogenetics, obstacles remain – chief among them the high cost of developing drugs and the limitations of a multi-payer system.

The use of the omics tools is a powerful way to detect, discover and eventually implement treatment for a vast array of CV and cardiometabolic diseases. The novel technologies discussed in the recent issue of Circulation Research may help identify the genetic bases of metabolic variation among individuals and provide us with previously unknown associations between biological pathways and clinical expression of diseases at an individual level. The era of "precision medicine" is an exciting time in which we can explore different pathways in the effort to eradicate atherosclerosis and associated cardiovascular diseases.

Author

Anum Saeed, MD

Anum Saeed, MD, is a Cardiovascular Diseases fellow at the University of Pittsburgh Medical Center in Pittsburgh, PA. Her research interests are in atherosclerosis, lipids and CVD prevention. She enjoys tennis, exploring new restaurants and volunteering for academic cardiology organizations.