1 / 11

Ed O’ Brien, Jean-Claude Bakala-N’Goma, Chunhua Shi Cumming School of Medicine

Explore how Heat Shock Protein 27 (HSP27) reduces PCSK9 expression, increases LDL receptor levels, and decreases plasma cholesterol, offering potential therapeutic strategies for atherosclerosis and hypercholesterolemia. Collaborative research by the O'Brien Lab at the Cumming School of Medicine investigates the atheroprotective properties of HSP27 and its role in cardiovascular health.

cgilliam
Download Presentation

Ed O’ Brien, Jean-Claude Bakala-N’Goma, Chunhua Shi Cumming School of Medicine

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Novel Reduction of PCSK9 Expression: Mechanistic Insights into the Anti-Atherosclerotic & Hypolipidemic Effects of Heat Shock Protein 27 Ed O’Brien, Jean-Claude Bakala-N’Goma, Chunhua Shi Cumming School of Medicine ermobrie@ucalgary.ca

  2. Heat Shock Protein 27 (HSP27) • Traditionally viewed as an intracellular chaperone protein • Estrogens increase synthesis & secretion (exosomes) • Extracellular levels are inversely related to atherosclerosis • Anti-atherogenic effects include: anti-apoptosis, anti-inflammatory, lipid lowering (serum / plaque), etc. • Signal from the “outside – in” via TLR4, etc. • Emerging role of anti-HSP27 auto-antibodies

  3. Serum HSP27 Levels Are Lower in Patients With CAD T. Seibert et al. J Am Coll Cardiol. 2013;62(16):1446-1454

  4. Serum HSP27 Levels Are Predictive of Future Cardiovascular Events T. Seibert et al. J Am Coll Cardiol. 2013;62(16):1446-1454

  5. Hypothesis HSP27 augments hepatic cholesterol uptake by reducing the expression of PCSK9 thereby increasing the availability of hepatic LDL-R.

  6. Proprotein Convertase Subtilisin / Kexin type 9 (PCSK9) Statins

  7. A rHSP27 PBS Heat Shock Protein 27 Reduces PCSK9 & Increases LDL Receptor Protein Levels in HepG2 Liver Cells rHSP27 PBS LDLR PCSK9 β-Actin β-Actin 54% P= 0.019 PCSK9 protein level (% vs β-Actin) LDLR protein level (% vs β-Actin) 67% P=0.001 PBS rHSP27

  8. Heat Shock Protein 27 Reduces Plasma PCSK9 Protein Levels & Increases LDL Receptor Levels in ApoE -/- mice 57% Plasma PCSK9 (ng/ml) rHSP27 PBS LDLR β-Actin 51% LDLR protein level (% vs β-Actin) rHSP27 PBS P= 0.001 P= 0.003

  9. Summary • HSP27 serum levels are athero-protective • HSP27 reduces PCSK9 & increases LDL-R expression • HSP27 reduces plasma cholesterol levels without altering HMG Co-A reductase or SREBP-2

  10. Future Implications • Mechanism by which HSP27 reduces PCSK9? • Role of Anti-HSP27 Auto-antibodies? • HSP27 therapeutic strategies for hypercholesterolemia & atherosclerosis? • HSP27 acts as a downstream “foot-soldier” of estrogen: >>> mechanism of post-menopausal increase in PCSK9?

  11. Research Team CUMMING SCHOOL OF MEDICINE O’Brien Lab • Yong-Xiang Chen MD, PhD • Chunhua (Scott) Shi, PhD • ZarahBatulan, PhD • Yumei(Tony) Li, (PhD) • Nadia Maarouf, (PhD) • Daiana Alvarez-Olmeda (PhD) • Li Zhang, PhD • Michael Chiu, MD • Yuan (Peter) Zhang (MD) • GeremyKoumbadinga, PhD • AyinuerAdijiang, PhD • VivekKrishan, PhD • Jean-Claude BakalaN’Goma, PhD • Collaborations: • Jackie de Belleroche (Imperial College London) • Bill Gerthoffer(Univ S. Alabama) • Jonathan Dean (Kennedy Institute Rheumatology, Oxford) • Gillian Einstein (U of Toronto) www.vascularnetwork.ca

More Related