Abstract 14072: Novel Atheroprotection Therapy: Reduction in Serum Lipid Levels by HSP27 Via Down-regulation of HNF1a and PCSK9 Expression

Background: Heat Shock Protein 27 (HSP27) levels are reduced in patients with CAD and are predictive of future cardiovascular risk. Experimental atherogenesis is attenuated when HSP27 levels are augmented - likely due to observed reductions in serum and plaque cholesterol levels. Recently we noted that HSP27 lowers the expression of PCSK9 and increases LDL-R levels. Moreover, we noted the presence of serum auto-antibodies (AAbs) to HSP27 that obfuscate the ELISA measurement of HSP27 levels and therefore developed a new mass spectrometry based assay to more accurately assess HSP27 levels (reported separately, HSP27 levels are 100-fold higher with MS). In recent in vitro studies we uncovered the mechanism by which these AAbs potentiate HSP27 signaling. Purpose #1: Determine how HSP27 attenuates PCSK9 levels, including its potential impact on HNF1a, an important transcriptional regulator of PCSK9. Purpose #2: Test the hypothesis that immunization to augment AAbs might reduce atherogenesis and ameliorate lipi...