New “One-Two Punch” to Fight Atherosclerosis
HSP27 Vaccination Lowers Cholesterol AND Inflammation
Novel mechanism for upregulated LDL-R expression, lowering of PCSK9 and reduction in systemic, plaque and hepatic inflammatory biomarkers.
Now in press at ATVB: https://www.ahajournals.org/doi/10.1161/ATVBAHA.121.315933
HSP27 combines with anti-HSP27 IgG antibodies to form immune complexes that dock at the hepatocyte cell membrane, engage the receptor TLR4, activate the NF-kB pathway and upregulate the expression of the LDL-R (independent of SREBP2). Plasma LDL cholesterol and PCSK9 levels fall because of the increased clearance by the more abundant LDL-Rs.
Inflammation biomarkers are markedly reduced in:
– blood (serum amyloid A levels drop >70%)
– liver (cytokines: IL-1beta, TNF-alpha)
– plaque (fewer macrophages & cholesterol crystals)
Net result: reduction in atherosclerosis