Metabolomics Approach to Identify Molecules and Pathways Involved in the Development of Atherosclerotic Coronary Artery Disease

ABSTRACT: Genetics play major roles in the development of atherosclerotic coronary artery disease (CAD). Despite tremendous efforts worldwide invested to decipher the genetic components controlling the development of CAD, the genetic architecture of CAD remains largely unclear. As part of an on-going effort to identify molecules and pathways involved in the development of atherosclerotic CAD, we propose to use rigorous angiographic criteria to define CAD phenotype for genomics and metabolomics study. We identified two extreme groups, namely “young CAD” group, who are very young individuals (age <= 40 years) proven to have severe CAD required revascularization, and “CAD-free elderly”, who are at very advanced age (Age >= 80 years) but have no angiographically apparent CAD. Phenotypically, these two groups are in sharp contrary. Conventional risk factors account for small portion of different phenotypes. We hypothesize that there are genetically programmed pathways and molecules accelerating atherosclerotic pathogenesis, in the “young CAD” patients and preventing the development of CAD in the “CAD-free elderly” patients. We sought to combine genomics and metabolomics approaches to profile and identify these pathways and molecules. Both plasma and urine samples from patients in these two groups, and their age matched control groups, will undergo unbiased metabolomics profiling with high throughput quantitative nuclear magnetic resonance (NMR) and mass spectrometry (MS) technology in RTI metabolomics core facility. Comprehensive statistic and multi-variant analytic approaches will be used to identify pathways and molecules significance to the pathogenesis of atherosclerosis. These data will be integrated with genomics data from next generation sequencing of genetic materials from the same groups of patients to further explore the molecular mechanisms underlying atherosclerosis and CAD.

ORGANISM(S): Human Homo Sapiens

TISSUE(S): Blood

SUBMITTER: Susan Sumner  

PROVIDER: ST000306 | MetabolomicsWorkbench | Thu Dec 31 00:00:00 GMT 2015

REPOSITORIES: MetabolomicsWorkbench