Ellagic acid, a functional food component, ameliorates functionality of reverse cholesterol transport in murine model of atherosclerosis
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
BACKGROUND/OBJECTIVES High levels of plasma low-density lipoprotein (LDL) cholesterol are an important determinant of atherosclerotic lesion formation. The disruption of cholesterol efflux or reverse cholesterol transport (RCT) in peripheral tissues and macrophages may promote atherogenesis. The aim of the current study was to examine whether bioactive ellagic acid, a functional food component, improved RCT functionality and high-density lipoprotein (HDL) function in diet-induced atherogenesis of apolipoproteins E (apoE) knockout (KO) mice. MATERIALS/METHODS Wild type mice and apoE KO mice were fed a high-cholesterol Paigen diet for 10 weeks to induce hypercholesterolemia and atherosclerosis, and concomitantly received 10 mg/kg ellagic acid via gavage. RESULTS Supplying ellagic acid enhanced induction of apoE and ATP-binding cassette (ABC) transporter G1 in oxidized LDL-exposed macrophages, facilitating cholesterol efflux associated with RCT. Oral administration of ellagic acid to apoE KO mice fed on Paigen diet improved hypercholesterolemia with reduced atherogenic index. This compound enhanced the expression of ABC transporters in peritoneal macrophages isolated from apoE KO mice fed on Paigen diet, indicating increased cholesterol efflux. Plasma levels of cholesterol ester transport protein and phospholipid transport protein involved in RCT were elevated in mice lack of apoE gene, which was substantially reduced by supplementing ellagic acid to Paigen diet-fed mice. In addition, ellagic acid attenuated hepatic lipid accumulation in apoE KO mice, evidenced by staining of hematoxylin and eosin and oil red O. Furthermore, the supplementation of 10 mg/kg ellagic acid favorably influenced the transcriptional levels of hepatic LDL receptor and scavenger receptor-B1 in Paigen diet-fed apoE KO mice. CONCLUSION Ellagic acid may be an athero-protective dietary compound encumbering diet-induced atherogenesis though improving the RCT functionality.
Abstract
BACKGROUND/OBJECTIVES High levels of plasma low-density lipoprotein (LDL) cholesterol are an important determinant of atherosclerotic lesion formation. The disruption of cholesterol efflux or reverse cholesterol transport (RCT) in peripheral tissues and macrophages may promote atherogenesis. The aim of the current study was to examine whether bioactive ellagic acid, a functional food component, improved RCT functionality and high-density lipoprotein (HDL) function in diet-induced atherogenesis of apolipoproteins E (apoE) knockout (KO) mice. MATERIALS/METHODS Wild type mice and apoE KO mice were fed a high-cholesterol Paigen diet for 10 weeks to induce hypercholesterolemia and atherosclerosis, and concomitantly received 10 mg/kg ellagic acid via gavage. RESULTS Supplying ellagic acid enhanced induction of apoE and ATP-binding cassette (ABC) transporter G1 in oxidized LDL-exposed macrophages, facilitating cholesterol efflux associated with RCT. Oral administration of ellagic acid to apoE KO mice fed on Paigen diet improved hypercholesterolemia with reduced atherogenic index. This compound enhanced the expression of ABC transporters in peritoneal macrophages isolated from apoE KO mice fed on Paigen diet, indicating increased cholesterol efflux. Plasma levels of cholesterol ester transport protein and phospholipid transport protein involved in RCT were elevated in mice lack of apoE gene, which was substantially reduced by supplementing ellagic acid to Paigen diet-fed mice. In addition, ellagic acid attenuated hepatic lipid accumulation in apoE KO mice, evidenced by staining of hematoxylin and eosin and oil red O. Furthermore, the supplementation of 10 mg/kg ellagic acid favorably influenced the transcriptional levels of hepatic LDL receptor and scavenger receptor-B1 in Paigen diet-fed apoE KO mice. CONCLUSION Ellagic acid may be an athero-protective dietary compound encumbering diet-induced atherogenesis though improving the RCT functionality.
참고문헌 (38)
- Frostegård J, "Immunity, atherosclerosis and cardiovascular disease", BMC Med, 11, pp.117~ (2013)
- Valanti EK, "Advances in biological therapies for dyslipidemias and atherosclerosis", Metabolism, 116, pp.154461~ (2021)
- Glass CK, "Atherosclerosis. the road ahead", Cell, 104, pp.503~516 (2001)
- Soliman GA, "Dietary cholesterol and the lack of evidence in cardiovascular disease", Nutrients, 10, pp.780~ (2018)
- Nelson RH, "Hyperlipidemia as a risk factor for cardiovascular disease", Prim Care, 40, pp.195~211 (2013)
- Ohashi R, "Reverse cholesterol transport and cholesterol efflux in atherosclerosis", QJM, 98, pp.845~856 (2005)
- Joyce CW, "The ATP binding cassette transporter A1(ABCA1)modulates the development of aortic atherosclerosis in C57BL", 6 and apoE-knockout mice, 2002, pp.99, 407~412
- Rohatgi A, "Reverse cholesterol transport and atherosclerosis", Arterioscler Thromb Vasc Biol, 39, pp.2~4 (2019)
- Getz GS, "Apoprotein E and reverse cholesterol transport", Int J Mol Sci, 19, pp.3479~ (2018)
- Wang HH, "Cholesterol and lipoprotein metabolism and atherosclerosis : recent advances in reverse cholesterol transport", Ann Hepatol, 16, pp.s27~42 (2017)
- Cuchel M, "Macrophage reverse cholesterol transport : key to the regression of atherosclerosis", Circulation, 113, pp.2548~2555 (2006)
- Wang N, "Regulation and mechanisms of ATP-binding cassette transporter A1-mediated cellular cholesterol efflux", Arterioscler Thromb Vasc Biol, 23, pp.1178~1184 (2003)
- Dallinga-Thie GM, "Concerted actions of cholesteryl ester transfer protein and phospholipid transfer protein in type 2 diabetes : effects of apolipoproteins", Curr Opin Lipidol, 18, pp.251~257 (2007)
- Shrestha S, "Cholesteryl ester transfer protein and its inhibitors", J Lipid Res, 59, pp.772~783 (2018)
- Luo Y, "Pharmacologic inhibition of phospholipid transfer protein activity reduces apolipoprotein-B secretion from hepatocytes", J Pharmacol Exp Ther, 332, pp.1100~1106 (2010)
- Dove DE, "ApoE-mediated cholesterol efflux from macrophages : separation of autocrine and paracrine effects", Am J Physiol Cell Physiol, 288, pp.C586~92 (2005)
- Oppi S, "Mouse models for atherosclerosis research-which is my line", Front Cardiovasc Med, 6, pp.46~ (2019)
- Greenow K, "The key role of apolipoprotein E in atherosclerosis", J Mol Med(Berl), 83, pp.329~342 (2005)
- Meir KS, "Atherosclerosis in the apolipoprotein-E-deficient mouse : a decade of progress", Arterioscler Thromb Vasc Biol, 24, pp.1006~1014 (2004)
- Su YR, "Macrophage apolipoprotein A-I expression protects against atherosclerosis in ApoE-deficient mice and up-regulates ABC transporters", Mol Ther, 8, pp.576~583 (2003)
- Derosa G, "Ellagic acid and its role in chronic diseases", Adv Exp Med Biol, 928, pp.473~479 (2016)
- Larrosa M, "Ellagitannins, ellagic acid and vascular health", Mol Aspects Med, 31, pp.513~539 (2010)
- Lee WJ, "Ellagic acid inhibits oxidized LDL-mediated LOX-1 expression, ROS generation, and inflammation in human endothelial cells", J Vasc Surg, 52, pp.1290~1300 (2010)
- Park SH, "Dietary ellagic acid attenuates oxidized LDL uptake and stimulates cholesterol efflux in murine macrophages", J Nutr, 141, pp.1931~1937 (2011)
- Khateeb J, "Paraoxonase 1(PON1)expression in hepatocytes is upregulated by pomegranate polyphenols : a role for PPAR-gamma pathway", Atherosclerosis, 208, pp.119~125 (2010)
- Phillips MC, "Molecular mechanisms of cellular cholesterol efflux", J Biol Chem, 289, pp.24020~24029 (2014)
- Zaiou M, "Apolipoprotein E;-low density lipoprotein receptor interaction. Influences of basic residue and amphipathic α-helix organization in the ligand", J Lipid Res, 41, pp.1087~1095 (2000)
- Zhang SH, "Diet-induced atherosclerosis in mice heterozygous and homozygous for apolipoprotein E gene disruption", J Clin Invest, 94, pp.937~945 (1994)
- Penson PE, "Natural compounds as anti-atherogenic agents : clinical evidence for improved cardiovascular outcomes", Atherosclerosis, 316, pp.58~65 (2021)
- Sedighi M, "A review of plant-based compounds and medicinal plants effective on atherosclerosis", J Res Med Sci, 22, pp.30~ (2017)
- Li RL, "Natural flavonoids derived from fruits are potential agents against atherosclerosis", Front Nutr, 9, pp.862277~ (2022)
- Lutz M, "Roles of phenolic compounds in the reduction of risk factors of cardiovascular diseases", Molecules, 24, pp.366~ (2019)
- Ríos JL, "A pharmacological update of ellagic acid", Planta Med, 84, pp.1068~1093 (2018)
- Ouimet M, "HDL and reverse cholesterol transport : basic mechanisms and their roles in vascular health and disease", Circ Res, 124, pp.1505~1518 (2019)
- Shen WJ, "SR-B1 : a unique multifunctional receptor for cholesterol influx and efflux", Annu Rev Physiol, 80, pp.95~116 (2018)
- Mardones P, "Hepatic cholesterol and bile acid metabolism and intestinal cholesterol absorption in scavenger receptor class B type I-deficient mice", J Lipid Res, 42, pp.170~180 (2001)
- Wang Z, "The LOX-1 receptor ectopically expressed in the liver alleviates atherosclerosis by clearing Ox-LDL from the circulation", Mol Med, 28, pp.26~ (2022)
- Basso F, "Role of the hepatic ABCA1 transporter in modulating intrahepatic cholesterol and plasma HDL cholesterol concentrations", J Lipid Res, 44, pp.296~302 (2003)