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)
October 2019 BBA General Subjects publication from the O’Brien lab advances the knowledge base for understanding the interaction of anti-HSP27 antibodies with HSP27. Such HSP27 immune complexes are involved in extra-cellular cellular signalling that results in the reduction in atherogenesis, cholesterol levels and inflammation.
“Biophysical analyses and functional implications of the interaction between heat shock protein 27 and antibodies to HSP27” by: Michael H. Chiu, Chunhua Shi, Matthew Rosin, Zarah Batulan, Edward R. O’Brien
The structure of HSP27 was modeled using the PHYRE Protein Fold Recognition Server, intensive mode, generating a 3D structure in which 174 aa (85% of the total 205 aa sequence) were modeled at >90% accuracy.
Thanks for the excellent feedback and questions regarding my presentation at ESC 2019 in Paris (Sept. 3rd), entitled “HSP25 Immunotherapy Post-Menopause is Superior to Estradiol in Targeting Atherosclerosis”. There is a real opportunity for the development of HSP27 immune-facilitated therapeutics for the reduction of both cholesterol and inflammation – particularly for post-menopausal women who are at increased risk of cardiovascular events. Stay tuned for new developments in our HSP27 vaccination pipeline.