Login Register Cart 0
Generic placeholder image

Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Review Article

Efferocytosis and Metabolic Syndrome: A Narrative Review

Author(s): Ali Amirinejad, Sayyed Saeid Khayyatzadeh, Noushin Rezaeivandchali and Seyed Mohammad Gheibihayat*

Volume 24, Issue 6, 2024

Published on: 10 July, 2023

Page: [751 - 757] Pages: 7

DOI: 10.2174/1566524023666230710120438

Price: $65

Abstract

Metabolic syndrome (MetS), which is distinguished by the simultaneous presence of hyperglycemia, dyslipidemia, hypertension, and central obesity, is a critical risk factor for cardiovascular disease (CVDs), mortality, and illness burden. Eliminating about one million cells per second in the human body, apoptosis conserves homeostasis and regulates the life cycle of organisms. In the physiological condition, the apoptotic cells internalize to the phagocytes by a multistep process named efferocytosis. Any impairment in the clearance of these apoptotic cells results in conditions related to chronic inflammation, such as obesity, diabetes, and dyslipidemia. On the other hand, insulin resistance and MetS can disturb the efferocytosis process. Since no study investigated the relationship between efferocytosis and MetS, we decided to explore the different steps of efferocytosis and describe how inefficient dead cell clearance is associated with the progression of MetS.

Keywords: Efferocytosis, metabolic syndrome, dyslipidemia, hyperglycemia, obesity efferocytosis, obesity.

« Previous Next »
[1]
Bennett JE, Stevens GA, Mathers CD, et al. NCD Countdown 2030: Worldwide trends in non-communicable disease mortality and progress towards Sustainable Development Goal target 3.4. Lancet 2018; 392(10152): 1072-88.
[http://dx.doi.org/10.1016/S0140-6736(18)31992-5] [PMID: 30264707]
[2]
Alberti KGMM, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome. Circulation 2009; 120(16): 1640-5.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.109.192644] [PMID: 19805654]
[3]
Saklayen MG. The global epidemic of the metabolic syndrome. Curr Hypertens Rep 2018; 20(2): 12-2.
[http://dx.doi.org/10.1007/s11906-018-0812-z] [PMID: 29480368]
[4]
Kerr JFR. History of the events leading to the formulation of the apoptosis concept. Toxicology 2002; 181-182: 471-4.
[http://dx.doi.org/10.1016/S0300-483X(02)00457-2] [PMID: 12505355]
[5]
Doran AC, Yurdagul A Jr, Tabas I. Efferocytosis in health and disease. Nat Rev Immunol 2020; 20(4): 254-67.
[http://dx.doi.org/10.1038/s41577-019-0240-6] [PMID: 31822793]
[6]
Ge Y, Huang M, Yao Y. Efferocytosis and its role in inflammatory disorders. Front Cell Dev Biol 2022; 10: 839248.
[http://dx.doi.org/10.3389/fcell.2022.839248] [PMID: 35281078]
[7]
Boada-Romero E, Martinez J, Heckmann BL, Green DR. The clearance of dead cells by efferocytosis. Nat Rev Mol Cell Biol 2020; 21(7): 398-414.
[http://dx.doi.org/10.1038/s41580-020-0232-1] [PMID: 32251387]
[8]
Elliott MR, Chekeni FB, Trampont PC, et al. Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature 2009; 461(7261): 282-6.
[http://dx.doi.org/10.1038/nature08296] [PMID: 19741708]
[9]
Lauber K, Bohn E, Kröber SM, et al. Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal. Cell 2003; 113(6): 717-30.
[http://dx.doi.org/10.1016/S0092-8674(03)00422-7] [PMID: 12809603]
[10]
Gude DR, Alvarez SE, Paugh SW, et al. Apoptosis induces expression of sphingosine kinase 1 to release sphingosine-1-phosphate as a “come-and-get-me” signal. FASEB J 2008; 22(8): 2629-38.
[http://dx.doi.org/10.1096/fj.08-107169] [PMID: 18362204]
[11]
Luo B, Gan W, Liu Z, et al. Erythropoeitin signaling in macrophages promotes dying cell clearance and immune tolerance. Immunity 2016; 44(2): 287-302.
[http://dx.doi.org/10.1016/j.immuni.2016.01.002] [PMID: 26872696]
[12]
Segawa K, Nagata S. An apoptotic ‘eat me’ signal: Phosphatidylserine exposure. Trends Cell Biol 2015; 25(11): 639-50.
[http://dx.doi.org/10.1016/j.tcb.2015.08.003] [PMID: 26437594]
[13]
Akakura S, Singh S, Spataro M, et al. The opsonin MFG-E8 is a ligand for the αvβ5 integrin and triggers DOCK180-dependent Rac1 activation for the phagocytosis of apoptotic cells. Exp Cell Res 2004; 292(2): 403-16.
[http://dx.doi.org/10.1016/j.yexcr.2003.09.011] [PMID: 14697347]
[14]
Freire-de-Lima CG, Xiao YQ, Gardai SJ, Bratton DL, Schiemann WP, Henson PM. Apoptotic cells, through transforming growth factor-beta, coordinately induce anti-inflammatory and suppress pro-inflammatory eicosanoid and NO synthesis in murine macrophages. J Biol Chem 2006; 281(50): 38376-84.
[http://dx.doi.org/10.1074/jbc.M605146200] [PMID: 17056601]
[15]
Rosales C, Uribe-Querol E. Phagocytosis: A fundamental process in immunity. Biomed Res Int 2017; 2017: 9042851.
[http://dx.doi.org/10.1155/2017/9042851]
[16]
Ma Z, Thomas KS, Webb DJ, et al. Regulation of Rac1 activation by the low density lipoprotein receptor–related protein. J Cell Biol 2002; 159(6): 1061-70.
[http://dx.doi.org/10.1083/jcb.200207070] [PMID: 12499359]
[17]
Park D, Tosello-Trampont AC, Elliott MR, et al. BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. Nature 2007; 450(7168): 430-4.
[http://dx.doi.org/10.1038/nature06329] [PMID: 17960134]
[18]
van Buul JD, Geerts D, Huveneers S. Rho GAPs and GEFs. Cell Adhes Migr 2014; 8(2): 108-24.
[http://dx.doi.org/10.4161/cam.27599] [PMID: 24622613]
[19]
Rink J, Ghigo E, Kalaidzidis Y, Zerial M. Rab conversion as a mechanism of progression from early to late endosomes. Cell 2005; 122(5): 735-49.
[http://dx.doi.org/10.1016/j.cell.2005.06.043] [PMID: 16143105]
[20]
Kanter JE, Hsu CC, Bornfeldt KE. Monocytes and macrophages as protagonists in vascular complications of diabetes. Front Cardiovasc Med 2020; 7: 10-0.
[http://dx.doi.org/10.3389/fcvm.2020.00010] [PMID: 32118048]
[21]
Giulietti A, van Etten E, Overbergh L, Stoffels K, Bouillon R, Mathieu C. Monocytes from type 2 diabetic patients have a pro-inflammatory profile. Diabetes Res Clin Pract 2007; 77(1): 47-57.
[http://dx.doi.org/10.1016/j.diabres.2006.10.007] [PMID: 17112620]
[22]
Han S, Liang CP, DeVries-Seimon T, et al. Macrophage insulin receptor deficiency increases ER stress-induced apoptosis and necrotic core formation in advanced atherosclerotic lesions. Cell Metab 2006; 3(4): 257-66.
[http://dx.doi.org/10.1016/j.cmet.2006.02.008] [PMID: 16581003]
[23]
Cash JG, Kuhel DG, Basford JE, et al. Apolipoprotein E4 impairs macrophage efferocytosis and potentiates apoptosis by accelerating endoplasmic reticulum stress. J Biol Chem 2012; 287(33): 27876-84.
[http://dx.doi.org/10.1074/jbc.M112.377549] [PMID: 22730380]
[24]
Achari A, Jain S. Adiponectin, a therapeutic target for obesity, diabetes, and endothelial dysfunction. Int J Mol Sci 2017; 18(6): 1321.
[http://dx.doi.org/10.3390/ijms18061321] [PMID: 28635626]
[25]
Waki H, Yamauchi T, Kamon J, et al. Impaired multimerization of human adiponectin mutants associated with diabetes. Molecular structure and multimer formation of adiponectin. J Biol Chem 2003; 278(41): 40352-63.
[http://dx.doi.org/10.1074/jbc.M300365200] [PMID: 12878598]
[26]
Abdolmaleki F, Kovanen PT, Mardani R, Gheibi-hayat SM, Bo S, Sahebkar A. Resolvins: Emerging players in autoimmune and inflammatory diseases. Clin Rev Allergy Immunol 2020; 58(1): 82-91.
[http://dx.doi.org/10.1007/s12016-019-08754-9] [PMID: 31267470]
[27]
Bathina S, Das UN. Resolvin D1 decreases severity of streptozotocin-induced type 1 diabetes mellitus by enhancing BDNF levels, reducing oxidative stress, and suppressing inflammation. Int J Mol Sci 2021; 22(4): 1516.
[http://dx.doi.org/10.3390/ijms22041516] [PMID: 33546300]
[28]
Iqbal J, Al Qarni A, Hawwari A, Alghanem AF, Ahmed G. Metabolic syndrome, dyslipidemia and regulation of lipoprotein metabolism. Curr Diabetes Rev 2018; 14(5): 427-33.
[http://dx.doi.org/10.2174/1573399813666170705161039] [PMID: 28677496]
[29]
Jackson WD, Weinrich TW, Woollard KJ. Very-low and low-density lipoproteins induce neutral lipid accumulation and impair migration in monocyte subsets. Sci Rep 2016; 6(1): 20038.
[http://dx.doi.org/10.1038/srep20038] [PMID: 26821597]
[30]
Tang C, Kanter JE, Bornfeldt KE, Leboeuf RC, Oram JF. Diabetes reduces the cholesterol exporter ABCA1 in mouse macrophages and kidneys. J Lipid Res 2010; 51(7): 1719-28.
[http://dx.doi.org/10.1194/jlr.M003525] [PMID: 19965614]
[31]
Mauldin JP, Nagelin MH, Wojcik AJ, et al. Reduced expression of ATP-binding cassette transporter G1 increases cholesterol accumulation in macrophages of patients with type 2 diabetes mellitus. Circulation 2008; 117(21): 2785-92.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.107.741314] [PMID: 18490524]
[32]
Griffin E, Re A, Hamel N, et al. A link between diabetes and atherosclerosis: Glucose regulates expression of CD36 at the level of translation. Nat Med 2001; 7(7): 840-6.
[http://dx.doi.org/10.1038/89969] [PMID: 11433350]
[33]
Nagareddy PR, Murphy AJ, Stirzaker RA, et al. Hyperglycemia promotes myelopoiesis and impairs the resolution of atherosclerosis. Cell Metab 2013; 17(5): 695-708.
[http://dx.doi.org/10.1016/j.cmet.2013.04.001] [PMID: 23663738]
[34]
Yvan-Charvet L, Pagler T, Gautier EL, et al. ATP-binding cassette transporters and HDL suppress hematopoietic stem cell proliferation. Science 2010; 328(5986): 1689-93.
[http://dx.doi.org/10.1126/science.1189731] [PMID: 20488992]
[35]
Rahman K, Vengrenyuk Y, Ramsey SA, et al. Inflammatory Ly6Chi monocytes and their conversion to M2 macrophages drive atherosclerosis regression. J Clin Invest 2017; 127(8): 2904-15.
[http://dx.doi.org/10.1172/JCI75005] [PMID: 28650342]
[36]
Wang H, Ye J. Regulation of energy balance by inflammation: Common theme in physiology and pathology. Rev Endocr Metab Disord 2015; 16(1): 47-54.
[http://dx.doi.org/10.1007/s11154-014-9306-8] [PMID: 25526866]
[37]
Fernandez-Boyanapalli R, Goleva E, Kolakowski C, et al. Obesity impairs apoptotic cell clearance in asthma. J Allergy Clin Immunol 2013; 131: 1041-7.
[http://dx.doi.org/10.1016/j.jaci.2012.09.028]
[38]
Luo B, Wang Z, Zhang Z, Shen Z, Zhang Z. The deficiency of macrophage erythropoietin signaling contributes to delayed acute inflammation resolution in diet-induced obese mice. Biochim Biophys Acta Mol Basis Dis 2019; 1865(2): 339-49.
[http://dx.doi.org/10.1016/j.bbadis.2018.10.005] [PMID: 30292638]
[39]
Moon MH, Jeong JK, Park SY. Activation of S1P2 receptor, a possible mechanism of inhibition of adipogenic differentiation by sphingosine 1-phosphate. Mol Med Rep 2015; 11(2): 1031-6.
[http://dx.doi.org/10.3892/mmr.2014.2810] [PMID: 25351259]
[40]
Rath M, Müller I, Kropf P, Closs EI, Munder M. Metabolism via Arginase or Nitric Oxide Synthase: Two Competing Arginine Pathways in Macrophages. Front Immunol 2014; 5: 532.
[http://dx.doi.org/10.3389/fimmu.2014.00532] [PMID: 25386178]
[41]
Takemura Y, Ouchi N, Shibata R, et al. Adiponectin modulates inflammatory reactions via calreticulin receptor–dependent clearance of early apoptotic bodies. J Clin Invest 2007; 117(2): 375-86.
[http://dx.doi.org/10.1172/JCI29709] [PMID: 17256056]
[42]
Galvan MD, Hulsebus H, Heitker T, Zeng E, Bohlson SS. Complement protein C1q and adiponectin stimulate Mer tyrosine kinase-dependent engulfment of apoptotic cells through a shared pathway. J Innate Immun 2014; 6(6): 780-92.
[http://dx.doi.org/10.1159/000363295] [PMID: 24942043]
[43]
Apovian CM, Bigornia S, Mott M, et al. Adipose macrophage infiltration is associated with insulin resistance and vascular endothelial dysfunction in obese subjects. Arterioscler Thromb Vasc Biol 2008; 28(9): 1654-9.
[http://dx.doi.org/10.1161/ATVBAHA.108.170316] [PMID: 18566296]
[44]
Huang ZH, Manickam B, Ryvkin V, et al. PCOS is associated with increased CD11c expression and crown-like structures in adipose tissue and increased central abdominal fat depots independent of obesity. J Clin Endocrinol Metab 2013; 98(1): E17-24.
[http://dx.doi.org/10.1210/jc.2012-2697] [PMID: 23118428]
[45]
Yvan-Charvet L, Pagler TA, Seimon TA, et al. ABCA1 and ABCG1 protect against oxidative stress-induced macrophage apoptosis during efferocytosis. Circ Res 2010; 106(12): 1861-9.
[http://dx.doi.org/10.1161/CIRCRESAHA.110.217281] [PMID: 20431058]
[46]
Bojic LA, Sawyez CG, Telford DE, Edwards JY, Hegele RA, Huff MW. Activation of peroxisome proliferator-activated receptor δ inhibits human macrophage foam cell formation and the inflammatory response induced by very low-density lipoprotein. Arterioscler Thromb Vasc Biol 2012; 32(12): 2919-28.
[http://dx.doi.org/10.1161/ATVBAHA.112.255208] [PMID: 23023367]
[47]
Palomer X, Barroso E, Pizarro-Delgado J, et al. PPARβ/δ: A key therapeutic target in metabolic disorders. Int J Mol Sci 2018; 19(3): 913.
[http://dx.doi.org/10.3390/ijms19030913] [PMID: 29558390]
[48]
Schulman IG. Liver X receptors link lipid metabolism and inflammation. FEBS Lett 2017; 591(19): 2978-91.
[http://dx.doi.org/10.1002/1873-3468.12702] [PMID: 28555747]
[49]
Wilkinson IB, Prasad K, Hall IR, et al. Increased central pulse pressure and augmentation index in subjects with hypercholesterolemia. J Am Coll Cardiol 2002; 39(6): 1005-11.
[http://dx.doi.org/10.1016/S0735-1097(02)01723-0] [PMID: 11897443]

Rights & Permissions Print Cite
Article Metrics
19
2
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy