Development of an Advanced System of Vascular Inflammation: Genome-Wide Profiling of Human Vascular Response to Oxidized Lipoproteins

This grant was awarded by the National Heart, Lung, and Blood Institute of the NIH in April 2010. This Phase I SBIR grant funded the development of a system using the HemoShear technology that replicates the onset of inflammation in arteries, allowing pharmaceutical companies to identify new targets and test compounds for cardiovascular efficacy and safety under atherosclerotic conditions. The comprehensive genomic database generated by the system has revealed novel, relevant molecular targets for therapeutic intervention in vascular inflammation. This database is valuable to companies developing cardiovascular drugs or assessing risk of off-target vascular effects of other drug-classes/indications.

Specific Aims

Aim 1: To determine the vascular endothelial and smooth muscle cell (EC/SMC) response to bioactive oxidized lipoproteins in a human surrogate model of inflammatory onset, e.g., early-stage atherosclerosis.

Aim 2: To generate a comprehensive EC/SMC genomic database profiling the integrated response to bioactive oxidized lipoproteins and hemodynamic forces.

Aim 3: To determine the global regulators of vascular inflammation using bioinformatics and computational systems biology analyses of EC/SMC genomic database.

Status Update: The Phase I work was successfully completed demonstrating that the presence of human pathophysiological levels of TNFa and oxidized LDL result in a profile of early stage inflammation that closely replicates in vivo biology. HemoShear is currently using the system in customer research collaborations.