Why the study?
Does ApoCIII and TRLs increase inflammation, ER stress, and oxidative stress in endothelial cells and macrophages in atherosclerosis models?
Does ApoCIII and TRLs increase inflammation, ER stress, and oxidative stress in endothelial cells and macrophages in atherosclerosis models?
Both TRLs and ApoCIII contribute to atherosclerosis progression by increasing inflammation, ER stress, and oxidative stress in endothelial cells and macrophages.
Adds mechanistic insight in mice; leaves open whether ApoCIII inhibition alters human atherosclerosis progression.
BACKGROUND: Overexpression of apolipoprotein CIII (ApoCIII) leads to hypertriglyceridemia (HTG) which promotes atherosclerosis development. However, it remains unclear whether ApoCIII affects the atherosclerosis alone by promoting the inflammation and endoplasmic reticulum (ER) stress, or in combination with HTG. METHODS: Transgenic (ApoCIIItg) mouse models were used to investigate the atherogenic role of ApoCIII. Since endothelial cells and macrophages play crucial roles in atherosclerosis, we examined whether triglyceride-rich lipoproteins (TRLs), the major lipoproteins, in plasma of ApoCIIItg mice affect inflammation and ER stress levels in these cells. To further investigate the role of ApoCIII and triglyceride, we incubated HUVECs cells and peritoneal macrophages with TRLs with or without ApoCIII. RESULTS: Increased inflammation and ER stress were found in the aorta of ApoCIIItg mice. TRLs increased ER stress and oxidative stress in HUVECs and macrophages in a dose dependent. Moreover, TRLs together with ApoCIII could induce a higher inflammation level than TRLs alone in these cells. CONCLUSIONS: Both TRLs and ApoCIII contribute to the progression of atherosclerosis, and the modulation of TRLs and ApoCIII may represent a novel therapeutic approach against HTG induced atherosclerosis.
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Ma et al. (2018) studied this question.
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