Cholesterol Archives - www.pemi31therapeutics.com

New “One-Two Punch” to Fight Atherosclerosis

by Ed O'Brien | Apr 5, 2021 | HSP27 immune complex, LDLR, Pemi31 Tx, Therapeutics, Vaccination

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

HSP27 Immune Complex Characterization: Latest Update into the Understanding of Novel Immune-facilitated Therapy

by Ed O'Brien | Sep 30, 2019 | HSP27 immune complex, Mechanism

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.