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)
Research on women’s heart & brain health is gaining momentum!
Heart disease and stroke are the #1 cause of premature death for women, but two-thirds of patient-related research involves men. Similarly, there are lost opportunities if basic research focuses only on male cells or male animal models. The Heart & Stroke Foundation of Canada is making significant changes to address this gap. For more information, click on the full report: “A Fighting Chance“
Exciting research from the O’Brien Lab strives to develop a vaccine to prevent and treat Hardening of the arteries in post-menopausal women
HSP27 (short for Heat Shock Protein 27) is a protein (substance) that is naturally made by your body, and was discovered as a ‘protector’ against inflammation and hardening of the arteries (‘atherosclerosis’). Women have higher levels of HSP27 – at least until menopause – when levels decline. This is because the hormone estrogen (made by a woman’s ovaries) promote the production of HSP27. However, after menopause the levels of estrogen and HSP27 decline. Interestingly, there are antibodies to HSP27 that are naturally present, and ‘stick to’ HSP27 and help make it ‘work better’. This has lead to exciting new HSP27 vaccination experiments that show promise in preventing or treating atherosclerosis. Whether HSP27 will have other beneficial effects on the health of post-menopausal women is now an active area of research.
Stay tuned for updates from our March 2020 presentation at the Keystone Symposium entitled “Transforming Vaccinology” (Florence, IT), co-sponsored by the Bill and Melinda Gates Foundation. Our presentation entitled “HSP27 Vaccination Reduces Cholesterol and Atherogenesis” highlights how HSP27 Vaccination may lead to increased expression of the liver receptor (LDLR) that takes cholesterol out of the blood, as well as reduce the abundance of another factor (PCSK9) that raises cholesterol levels.
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.
Grateful to be celebrated with my peers at the Libin Cardiovascular Institute of Alberta’s 6th Annual Gala. The community came together again to recognize and foster excellence in cardiovascular care and research.
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.