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Publications & IP

Publications

  1. HSP25 Vaccination Attenuates Atherogenesis via Upregulation of LDLR Expression, Lowering of PCSK9 Levels and Curbing of Inflammation. Y.-X. Chen, C. Shi, J. Deng, C. Diao, N. Maarouf, M. Rosin, V. Shrivastava, A. Hu, S. Bharadwa, A. Adijiang, A. Ulke-Lemee, B. Gwilym, A. Hellmich, C. Malozzi, Z. Batulan, J.L. E. Dean, F.D. Ramirez, J. Liu, W.T. Gerthoffer, E.R. O’Brien. Arteriosclerosis, Thrombosis & Vascular Biology; 2021 April 1;41:e338–e353
  2. Unlike estrogens that increase PCSK9 levels post-menopause HSP27 vaccination lowers cholesterol levels and atherogenesis due to divergent effects on PCSK9 and LDLR. Maarouf N, Chen YX, Shi C, Deng J, Diao C, Rosin M, Shrivastava V, Batulan Z, Liu J, O’Brien ER. Pharmacol Res. 2020 Nov;161:105222. 
  3. Heat shock protein 27 immune complex altered signaling and transport (ICAST): Novel mechanisms of attenuating inflammation. Shi C, Deng J, Chiu M, Chen YX, O’Brien ER.  FASEB J. 2020 Nov;34(11):14287-14301. 
  4. The Heat Shock Protein 27 Immune Complex Enhances Exosomal Cholesterol Efflux Shi C, Alvarez-Olmedo D, Zhang Y, Pattar BSB, O’Brien ER. Biomedicines. 2020 Aug 17;8(8):290.
  5. Role of Heat Shock Protein 27 in Modulating Atherosclerotic Inflammation. Inia JA, O’Brien ER. J Cardiovasc Transl Res. 2020 Jul 13. 
  6. Biophysical analyses and functional implications of the interaction between Heat Shock Protein 27 and antibodies to HSP27. Chiu MH, Shi C, Rosin M, Batulan Z, O’Brien ER. Biochim Biophys Acta Gen Subj. 2019 Oct;1863(10):1536-1546. 
  7. Characterization of heat shock protein 27 in extracellular vesicles: a potential anti-inflammatory therapy. Shi C, Ulke-Lemée A, Deng J, Batulan Z, O’Brien ER. FASEB J. 2019 Feb;33(2):1617-1630. 
  8. Heat shock protein 27-derived atheroprotection involves reverse cholesterol transport that is dependent on GM-CSF to maintain ABCA1 and ABCG1 expression in ApoE-/- mice. Pulakazhi Venu VK, Adijiang A, Seibert T, Chen YX, Shi C, Batulan Z, O’Brien ER. FASEB J. 2017 Jun;31(6):2364-2379.
  9. Extracellular Release and Signaling by Heat Shock Protein 27: Role in Modifying Vascular Inflammation. Batulan Z, Pulakazhi Venu VK, Li Y, Koumbadinga G, Alvarez-Olmedo DG, Shi C, O’Brien ER. Front Immunol. 2016 Jul 26;7:285. 
  10. Heat shock protein 27 attenuates neointima formation and accelerates reendothelialization after arterial injury and stent implantation: importance of vascular endothelial growth factor up-regulation. Ma X, Hibbert B, McNulty M, Hu T, Zhao X, Ramirez FD, Simard T, de Belleroche JS, O’Brien ER. FASEB J. 2014 Feb;28(2):594-602. 
  11. Heat shock protein-27 attenuates foam cell formation and atherogenesis by down-regulating scavenger receptor-A expression via NF-κB signaling. Raizman JE, Chen YX, Seibert T, Hibbert B, Cuerrier CM, Salari S, Zhao X, Hu T, Shi C, Ma X, Simard T, Caravaggio J, Rayner K, Bowdish D, Moore K, O’Brien ER. Biochim Biophys Acta. 2013 Dec;1831(12):1721-8. 
  12. Serum heat shock protein 27 levels represent a potential therapeutic target for atherosclerosis: observations from a human cohort and treatment of female mice. Seibert TA, Hibbert B, Chen YX, Rayner K, Simard T, Hu T, Cuerrier CM, Zhao X, de Belleroche J, Chow BJ, Hawken S, Wilson KR, O’Brien ER. J Am Coll Cardiol. 2013 Oct 15;62(16):1446-54. 
  13. Chronic over-expression of heat shock protein 27 attenuates atherogenesis and enhances plaque remodeling: a combined histological and mechanical assessment of aortic lesions. Cuerrier CM, Chen YX, Tremblay D, Rayner K, McNulty M, Zhao X, Kennedy CR, de Belle Roche J, Pelling AE, O’Brien ER. PLoS One. 2013;8(2):e55867. 
  14. Extracellular HSP27 acts as a signaling molecule to activate NF-κB in macrophages. Salari S, Seibert T, Chen YX, Hu T, Shi C, Zhao X, Cuerrier CM, Raizman JE, O’Brien ER. Cell Stress Chaperones. 2013 Jan;18(1):53-63. 
  15. Heat shock protein 27: clue to understanding estrogen-mediated atheroprotection? Rayner K, Chen YX, Siebert T, O’Brien ER. Trends Cardiovasc Med. 2010 Feb;20(2):54-8. 
  16. Heat shock protein 27 protects against atherogenesis via an estrogen-dependent mechanism: role of selective estrogen receptor beta modulation. Rayner K, Sun J, Chen YX, McNulty M, Simard T, Zhao X, Wells DJ, de Belleroche J, O’Brien ER. Arterioscler Thromb Vasc Biol. 2009 Nov;29(11):1751-6. doi: 10.1161/ATVBAHA.109.193656. 
  17. Extracellular release of the atheroprotective heat shock protein 27 is mediated by estrogen and competitively inhibits acLDL binding to scavenger receptor-A. Rayner K, Chen YX, McNulty M, Simard T, Zhao X, Wells DJ, de Belleroche J, O’Brien ER. Circ Res. 2008 Jul 18;103(2):133-41. 
  18. The interaction and cellular localization of HSP27 and ERbeta are modulated by 17beta-estradiol and HSP27 phosphorylation. Al-Madhoun AS, Chen YX, Haidari L, Rayner K, Gerthoffer W, McBride H, O’Brien ER. Mol Cell Endocrinol. 2007 May 30;270(1-2):33-42. doi: 10.1016/j.mce.2007.02.002.
  19. Modulation of estrogen signaling by the novel interaction of heat shock protein 27, a biomarker for atherosclerosis, and estrogen receptor beta: mechanistic insight into the vascular effects of estrogens. Miller H, Poon S, Hibbert B, Rayner K, Chen YX, O’Brien ER. Arterioscler Thromb Vasc Biol. 2005 Mar;25(3):e10-4. 

Intellectual Property

  1. United States Patent: 8,343,915  O’Brien et al., January 1, 2013
    Use of heat-shock protein 27 for cardiovascular disease prevention and treatment 
    Abstract: A method of preventing or treating cardiovascular disease is provided. The method comprises administering heat shock protein 27 (HSP27), a co-factor, variant or analogue thereof. The cardiovascular disease can include atherosclerosis. A pharmaceutical composition comprising HSP27 for use in the prevention or treatment of cardiovascular disease is also provided.
     
  2. United States Patent: 8,343,916  O’Brien et al., January 1, 2013
    Use of heat-shock protein 27 for cardiovascular disease prevention and treatment 
    Abstract: A method of reducing cholesterol in a subject is provided. The method may be used to decrease serum cholesterol and/or arterial wall cholesterol. The method comprises administering a therapeutically effective amount of heat shock protein 27 (HSP27), or a co-factor, variant or analogue thereof. The method may be used to treat, prevent or reverse cardiovascular disease (including atherosclerosis); to decrease atherosclerotic lesion formation or rupture; to decrease apoptosis within a plaque; to decrease macrophage accumulation; and/or to reverse the accumulation of atherosclerotic plaque mass in a subject. Kits and pharmaceutical compositions comprising HSP27 for preventing or treating of cardiovascular disease, such as atherosclerosis, are also provided.

  3. United States Patent: 11,439,696 B2  O’Brien et al., September 13, 2022
    Modulation of Proprotein Convertase Subtilisin/Kexin 9 Expression (PCSK9) with HSP27 and/or HSP25
    Abstract: This disclosure pertains to compositions for reducing Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) expression and for reducing serum cholesterol in mammalian subjects. The exemplary compositions comprise heat shock protein HSP27 or fragments thereof and/or a HSP25, or fragments thereof in a mixture with an adjuvant. The compositions may optionally comprise anti-HSP27 antibody. The method for reducing serum cholesterol relate to the use of the compositions to increase the subject’s levels of serum HSP27 and/or anti-HSP27 antibodies.
     
  4. United States Patent: 12,005,101  O’Brien et al., June 11, 2024 Abstract: Methods claims related to US Patent 11, 439,696 B2 (see above)
    Modulation of Proprotein Convertase Subtilisin/Kexin 9 Expression (PCSK9) with HSP27 and/or HSP25

  5. United States PCT Patent Application No. PCT/CA2021/050728 
    O’Brien et al., PCT submission May 28, 2021 
    International Publication Number: WO 2021/237366 A1 (Dec. 2, 2021)
    Treatment of Non-Alcoholic Fatty Liver Disease
    Abstract: Disclosed are methods for the treatment of non-fatty liver disease (NAFLD). The methods involve the administration to a subject in need thereof of a pharmaceutical formulation comprising an HSP27 polypeptide or immunologically equivalent portion thereof, or an anti-HSP27 antibody or a functional anti-HSP27 antibody fragment, or a mixture of an HSP27 polypeptide or immunologically equivalent portion thereof, and an anti-HSP27 antibody or a functional anti-HSP27 antibody fragment.  N.B. This application received a very favorable Written Opinion regarding patentability from the International Examining Authority (ISR/WO).