CETP Inhibition as a novel treatment to remove pathogen lipids and improve survival in sepsis

The goal of this project is to investigate genetic mechanisms that determine high-density lipoprotein particle (HDL) levels in sepsis. We have discovered a gene, called CETP, that appears to play a very important role in determining HDL levels during sepsis, and thereby contributes to whether or not a patient will survive the episode of sepsis. 

Publications:

  1. Deng H, Liang WY, Chen LQ, Yuen TH, Sahin B, Vasilescu DM, Trinder M, Walley K, Rensen PCN, Boyd JH, Brunham LR. CETP inhibition enhances monocyte activation and bacterial clearance and reduces streptococcus pneumonia-associated mortality in mice. JCI Insight. 2024 Apr 22;9(8):e173205.
  2. Trinder M, Wang Y, Madsen CM, Ponomarev T, Bohunek L, Daisely BA, Julia Kong H, Blauw LL, Nordestgaard BG, Tybjærg-Hansen A, Wurfel MM, Russell JA, Walley KR, Rensen PCN, Boyd JH, Brunham LR. Inhibition of Cholesteryl Ester Transfer Protein Preserves High-Density Lipoprotein Cholesterol and Improves Survival in Sepsis. Circulation. 2021 Mar 2;143(9):921-934
  3. Trinder M, Walley KR, Boyd JH, Brunham LR. Causal Inference for Genetically Determined Levels of High-Density Lipoprotein Cholesterol and Risk of Infectious Disease. Arterioscler Thromb Vasc Biol. 2020 Jan;40(1):267-278.
  4. Trinder M, Genga KR, Kong HJ, Blauw LL, Lo C, Li X, Cirstea M, Wang Y, Rensen PCN, Russell JA, Walley KR, Boyd JH, Brunham LR. Cholesteryl Ester Transfer Protein Influences High-Density Lipoprotein Levels and Survival in Sepsis. Am J Respir Crit Care Med. 2019 Apr 1;199(7):854-862.
  5. Genga KR, Trinder M, Kong HJ, Li X, Leung AKK, Shimada T, Walley KR, Russell JA, Francis GA, Brunham LR, Boyd JH. CETP genetic variant rs1800777 (allele A) is associated with abnormally low HDL-C levels and increased risk of AKI during sepsis. Sci Rep. 2018 Nov 13;8(1):16764.

 


First Nations land acknowledegement

Action on Sepsis operates on the traditional, ancestral, and unceded territory of the Coast Salish peoples — xʷməθkʷəy̓əm (Musqueam), Sḵwx̱wú7mesh (Squamish), and Səl̓ílwətaʔ/Selilwitulh (Tsleil-Waututh) Nations. We invite everyone to reflect on the traditional territories and land that they currently work and live on.


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