APL180 TFA (L-4F TFA) is an Apo-A1 mimetic peptide. APL180 TFA binds oxidized/oxidizable lipids with high affinity and sequesters pro-inflammatory oxidized lipids. APL180 TFA downregulates glycolysis-related genes and HIF-1α expression, and upregulates CD206 and Arginase. APL180 TFA inhibits atherosclerotic lesion progression and platelet aggregation. APL180 TFA attenuates adverse left ventricular remodeling and systolic dysfunction after myocardial infarction. APL180 TFA can be used for research on ovarian cancer [1] [2] [3].
In Vivo, APL180 (100 µg/day; i.v. via tail vein; once daily; 5 consecutive days) TFA starting 3 days after reperfused MI prevents progressive LV remodeling and suppresses pro-inflammatory Ly6Chi monocytes/macrophages in blood, spleen, and heart in mice[2]. APL180 (100 µg/day; i.v. via tail vein; once daily; 5 consecutive days) TFA does not alter cardiac function or monocyte/macrophage profiles in sham-operated mice[2]. APL180 (5 mg/kg; i.p.; before ethanol gavages) TFA does not produce behavioural changes in female Wistar rats subjected to alcohol binge drinking[3].
In Vitro, In thioglycolate-elicited C57BL/6 peritoneal macrophages, APL180 (50 µg/mL; overnight) suppresses M1 inflammatory/glycolytic markers and augments HIF-2α in M1-polarized cells without affecting M2-polarized HIF-2α[2]. In RAW 264.7 mouse macrophages, APL180 (50 µg/mL; overnight) suppresses M1-associated iNOS/CCL3 and glycolytic/HIF-1α markers while upregulating CD206 and arginase in M1-polarized cells[2]. APL180 (150-1,000 ng/mL) ex vivo dose-dependently improves the HII in human plasma samples, with 150 ng/mL sufficient to sequester most HII-affecting oxidized lipids[1].
References:
[1]. Watson CE, et al. Treatment of patients with cardiovascular disease with L-4F, an apo-A1 mimetic, did not improve select biomarkers of HDL function. J Lipid Res. 2011 Feb;52(2):361-73..
[2]. Hamid T, et al. The apolipoprotein AI mimetic L-4F attenuates monocyte activation and adverse cardiac remodeling after myocardial infarction. International journal of molecular sciences. 2020 May 15;21(10):3519.
[3]. López-Valencia L, et al. ApoAI-LPS aggregates are found in the frontal cortex of female rats after alcohol binge drinking: effects of ApoAI mimetic peptide on behaviour. IBRO Neuroscience Reports. 2023 Oct 1;15:S862.
In Vivo, APL180 (100 µg/day; i.v. via tail vein; once daily; 5 consecutive days) TFA starting 3 days after reperfused MI prevents progressive LV remodeling and suppresses pro-inflammatory Ly6Chi monocytes/macrophages in blood, spleen, and heart in mice[2]. APL180 (100 µg/day; i.v. via tail vein; once daily; 5 consecutive days) TFA does not alter cardiac function or monocyte/macrophage profiles in sham-operated mice[2]. APL180 (5 mg/kg; i.p.; before ethanol gavages) TFA does not produce behavioural changes in female Wistar rats subjected to alcohol binge drinking[3].
In Vitro, In thioglycolate-elicited C57BL/6 peritoneal macrophages, APL180 (50 µg/mL; overnight) suppresses M1 inflammatory/glycolytic markers and augments HIF-2α in M1-polarized cells without affecting M2-polarized HIF-2α[2]. In RAW 264.7 mouse macrophages, APL180 (50 µg/mL; overnight) suppresses M1-associated iNOS/CCL3 and glycolytic/HIF-1α markers while upregulating CD206 and arginase in M1-polarized cells[2]. APL180 (150-1,000 ng/mL) ex vivo dose-dependently improves the HII in human plasma samples, with 150 ng/mL sufficient to sequester most HII-affecting oxidized lipids[1].
References:
[1]. Watson CE, et al. Treatment of patients with cardiovascular disease with L-4F, an apo-A1 mimetic, did not improve select biomarkers of HDL function. J Lipid Res. 2011 Feb;52(2):361-73..
[2]. Hamid T, et al. The apolipoprotein AI mimetic L-4F attenuates monocyte activation and adverse cardiac remodeling after myocardial infarction. International journal of molecular sciences. 2020 May 15;21(10):3519.
[3]. López-Valencia L, et al. ApoAI-LPS aggregates are found in the frontal cortex of female rats after alcohol binge drinking: effects of ApoAI mimetic peptide on behaviour. IBRO Neuroscience Reports. 2023 Oct 1;15:S862.