VLDL and HDL attenuate endoplasmic reticulum and metabolic stress in HL-1 cardiomyocytes.

Sara Tekavec, Tjaša Sorčan, Mauro Giacca, Tadeja Režen

Biochimica et biophysica acta. Molecular and cell biology of lipids 2020 Aug

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Lipoproteins have a vital role in the development of metabolic and cardiovascular diseases ranging from protective to deleterious effects on target tissues. VLDL has been shown to induce lipotoxic lipid accumulation and exert a variety of negative effects on cardiomyocytes. Lipotoxicity and endoplasmic reticulum (ER) stress are proposed to be the mediators of damaging effects of metabolic diseases on cardiovascular system. We treated cardiomyocytes with lipoproteins to evaluate the adaptability of these cells to metabolic stress induced by starvation and excess of lipoproteins, and to evaluate the effect of lipoproteins and lipid accumulation on ER stress. VLDL reversed metabolic stress induced by starvation, while HDL did not. VLDL induced dose-dependent lipid accumulation in cardiomyocytes, which however did not result in reduced cell viability or induction of ER stress. Moreover, VLDL or HDL pre-treatment reduced ER stress in cardiomyocytes induced by tunicamycin and palmitic acid as measured by the expression of ER stress markers, even in conditions of increased lipid accumulation. VLDL and HDL induced activation of pro-survival ERK1/2 in cardiomyocytes; however, this activation was not involved in the protection against ER stress. Additionally, we observed that LDLR and VLDLR are regulated differently by lipoproteins and cellular stress, as lipoproteins induced VLDLR protein independently of the level of lipid accumulation. We conclude that VLDL is not a priori detrimental for cardiomyocytes and can even have beneficial effects, enabling cell survival under starvation and attenuating ER stress. Copyright © 2020 Elsevier B.V. All rights reserved.

Citation

Sara Tekavec, Tjaša Sorčan, Mauro Giacca, Tadeja Režen. VLDL and HDL attenuate endoplasmic reticulum and metabolic stress in HL-1 cardiomyocytes. Biochimica et biophysica acta. Molecular and cell biology of lipids. 2020 Aug;1865(8):158713