USING -OMICS TECHNOLOGIES TO DISCOVER NEW PATHOPHYSIOLOGICAL PATHWAYS FOR THE FOUR MAJOR CARDIOVASCULAR DISEASES – A TRANSLATIONAL APPROACH

Bakgrund:The four most common cardiovascular diseases (CVD) are myocardial infarction, ischemic stroke, heart failure and atrial fibrillation. Many patients suffer from more than one of these diseases because of known shared pathophysiology, such as atherosclerosis or impaired left ventricular (LV) function.

Målsättning:To use -omics technologies and functional studies in a translational fashion to investigate the molecular basis of pathophysiological pathways underlying one or more of these diseases with the hypothesis that we will find new pathways that will improve the understanding of the pathophysiology of CVDs.

Arbetsplan:Several Swedish epidemiological cohorts (SCAPIS, PIVUS, ULSAM, TwinGene, POEM, EpiHealth, COSM, SMC), include data on genomics, proteomics and metabolomics in more than 20,000 subjects. We will investigate the relationships of proteomic and metabolomic patterns with incident CVD, as well as with markers of subclinical CVD, such as LV hypertrophy, enlarged left atrium, impaired LV systolic or diastolic function, endothelial dysfunction, arterial stiffness and atherosclerosis.

The causal role of biomarkers will be evaluated by Mendelian randomization, and pathway analysis will be conducted. Interesting findings will be further evaluated by CRISPR-Cas9 knock-out of relevant genes in Zebrafish model systems.

Betydelse:The present translational research program with studies in humans and zebrafish will provide molecular characterization of new pathophysiological pathways for CVD. This would lead to new targets for drug development, as well improved risk prediction of high-risk individuals.