The class
CETP-derived peptide Seq-1 directly suppresses pro-fibrotic gene expression in liver cells beyond its role in the anti-CETP vaccine (Arch Med Res 2024)
Original title: CETP-derived Peptide Seq-1, the Key Component of HB-ATV-8 Vaccine Prevents Stress Responses, and Promotes Downregulation of Pro-Fibrotic Genes in Hepatocytes and Stellate Cells
The nasal vaccine HB-ATV-8, containing peptide Seq-1 derived from the carboxy-terminus of CETP, has previously been shown to reduce liver fibrosis, inflammation, and atherosclerotic plaque formation in animal models by inducing antibodies that inhibit CETP cholesterol transfer activity. This study tested whether Seq-1 also acts directly on liver cells independent of antibody-mediated CETP inhibition, using an in vitro HepG2 steatosis model and conditioned medium applied to hepatic stellate cells. Peptide Seq-1 treatment of steatotic HepG2 cells downregulated COL1A1, ACTA2, and TGF-beta gene expression and reduced COL1A1, MMP-2, and TIMP-2 protein expression, changes associated with extracellular matrix remodeling; the same effects were observed in hepatic stellate cells incubated with supernatant from Seq-1-treated steatotic HepG2 cells. The authors conclude these findings support HB-ATV-8 as a candidate treatment for NASH linked to cardiovascular disease.
Original abstract
Background: The nasal vaccine HB-ATV-8 has emerged as a promising approach for NAFLD (non-alcoholic fatty liver disease) and atherosclerosis prevention. HB-ATV-8 contains peptide seq-1 derived from the carboxy-end of the Cholesteryl Ester Transfer Protein (CETP), shown to reduce liver fibrosis, inflammation, and atherosclerotic plaque formation in animal models. Beyond the fact that this vaccine induces B-cell lymphocytes to code for antibodies against the seq-1 sequence, inhibiting CETP's cholesterol transfer activity, we have hypothesized that beyond the modulation of CETP activity carried out by neutralizing antibodies, the observed molecular effects may also correspond to the direct action of peptide seq-1 on diverse cellular systems and molecular features involved in the development of liver fibrosis.
Methods: The HepG2 hepatoma-derived cell line was employed to establish an in vitro steatosis model. To obtain a conditioned cell medium to be used with hepatic stellate cell (HSC) cultures, HepG2 cells were exposed to fatty acids or fatty acids plus peptide seq-1, and the culture medium was collected. Gene regulation of COL1A1, ACTA2, TGF-β, and the expression of proteins COL1A1, MMP-2, and TIMP-2 were studied.
Aim: To establish an in vitro steatosis model employing HepG2 cells that mimics molecular processes observed in vivo during the onset of liver fibrosis. To evaluate the effect of peptide Seq-1 on lipid accumulation and pro-fibrotic responses. To study the effect of Seq-1-treated steatotic HepG2 cell supernatants on lipid accumulation, oxidative stress, and pro-fibrotic responses in HSC.
Results And Conclusion: Peptide seq-1-treated HepG2 cells show a downregulation of COLIA1, ACTA2, and TGF-β genes, and a decreased expression of proteins such as COL1A1, MMP-2, and TIMP-2, associated with the remodeling of extracellular matrix components. The same results are observed when HSCs are incubated with peptide Seq-1-treated steatotic HepG2 cell supernatants. The present study consolidates the nasal vaccine HB-ATV-8 as a new prospect in the treatment of NASH directly associated with the development of cardiovascular disease.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.