title: The IL-24 gene protects human umbilical vein endothelial cells against H₂O₂-induced injury and may be useful as a treatment for cardiovascular disease.
abstract: The aim of the present study was to investigate the protective effects of interleukin-24 (IL-24) on hydrogen peroxide (H2O2)-induced vascular endothelial injury and to examine the association between IL-24 and cardiovascular disease. Human umbilical vein endothelial cells (HUVECs) were exposed to increasing concentrations of H2O2 in the presence or absence of IL-24, which was introduced via Lipofectamine® 2000-mediated transfection. The successful uptake of the IL-24 plasmid was confirmed by RT-PCR at 24 h post-transfection. The effects of H2O2 and IL-24 on the proliferation and migration of the HUVECs was determined using cell migration assays. Cell viability was determined using a Cell Counting Kit-8 (CCK-8). Apoptosis and the measurement of the intracellular reactive oxygen species (ROS) levels were determined by flow cytometry, and the levels of caspase-3, which is associated with apoptosis, were determined by western blot analysis. Real‑time PCR and western blot analysis were also used to measure the levels of multiple cardiovascular disease‑associated factors. In vivo experiments were also performed using a rat model of hypertension which was constructed by angiotensin II infusion using an osmotic pump. The mRNA and protein levels of IL-24 were measured in both the control and hypertensive rats; the effects of treatment with enalapril and nifedipine on the IL-24 levels were also examined. Our results revealed that IL-24 protected against the H2O2-mediated abnormal increase in HUVEC proliferation. IL-24 also antagonized H2O2 by reducing the content of ROS in the cells, thus decreasing cellular oxidative damage, improving the cellular survival rate, reducing apoptosis and decreasing the expression of cardiovascular disease-related factors. The results from our in vivo animal experiments revealed that IL-24 expression was lower in the hypertensive rats compared to the healthy controls. Additionally, the IL-24 levels increased following anti-hypertensive therapy. The findings of our study indicate that IL-24 protects against H2O2-mediated endothelial cell damage and may thus provide a novel therapeutic strategy for treatment of cardiovascular disease.
authors.affiliation: The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, P.R. China.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Bank of China Shanxi Branch, Taiyuan, Shanxi, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, P.R. China.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Chen
authors.affiliation: The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, P.R. China.
authors.forename: Jiyuan
authors.initials: J
authors.lastname: Lv
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007378:Interleukins / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000099180:Interleukin-24
chemical_list: D000959:Antihypertensive Agents; D006861:Hydrogen Peroxide; D007378:Interleukins; D017382:Reactive Oxygen Species; D000099180:Interleukin-24
references.citation: Free Radic Res Commun. 1993;19(3):203-13
references.pmid: 8244089
references.citation: Int J Clin Exp Med. 2014 Nov 15;7(11):4082-90
references.pmid: 25550917
references.citation: Biochem Biophys Res Commun. 2012 Nov 9;428(1):50-5
references.pmid: 23063979
references.citation: Circ Res. 1995 Sep;77(3):445-65
references.pmid: 7641318
references.citation: Histochem Cell Biol. 2004 Oct;122(4):339-52
references.pmid: 15338229
references.citation: Cancer Res. 2003 Aug 15;63(16):5105-13
references.pmid: 12941841
references.citation: Am J Physiol Heart Circ Physiol. 2003 May;284(5):H1744-50
references.pmid: 12595301
references.citation: Circ Res. 1992 Mar;70(3):593-9
references.pmid: 1371430
references.citation: BJU Int. 2010 Mar;105(6):877-83
references.pmid: 19689474
references.citation: Hypertension. 2015 Jun;65(6):1316-23
references.pmid: 25870197
references.citation: Clin Cancer Res. 2003 Aug 15;9(9):3272-81
references.pmid: 12960112
references.citation: J Clin Oncol. 2002 Feb 15;20(4):1069-74
references.pmid: 11844832
references.citation: Med Hypotheses. 1998 May;50(5):393-8
references.pmid: 9681918
references.citation: Am J Physiol Heart Circ Physiol. 2005 May;288(5):H2177-84
references.pmid: 15626687
references.citation: J Atheroscler Thromb. 1998;4(3):118-27
references.pmid: 9730143
references.citation: Biofactors. 1998;8(1-2):1-5
references.pmid: 9699000
references.citation: Oncotarget. 2015 Nov 10;6(35):36928-42
references.pmid: 26474456
references.citation: Arch Biochem Biophys. 2000 Jan 1;373(1):242-8
references.pmid: 10620344
references.citation: Blood Press. 2007;16(3):135-232
references.pmid: 17846925
references.citation: Am J Clin Pathol. 2001 Dec;116 Suppl:S97-107
references.pmid: 11993705
references.citation: Adv Exp Med Biol. 2014;818:127-53
references.pmid: 25001534
references.citation: Pharmacol Ther. 2006 Jul;111(1):81-98
references.pmid: 16288809
references.citation: Pharmacology. 2012;90(5-6):332-41
references.pmid: 23052189
references.citation: J Interferon Cytokine Res. 2014 Sep;34(9):659-66
references.pmid: 24552169
references.citation: Int J Mol Med. 1998 May;1(5):827-34
references.pmid: 9852303
references.citation: Hepatol Res. 2010 Jan 1;40(1):95-104
references.pmid: 19737316
references.citation: Nucleic Acids Res. 2001 May 1;29(9):e45
references.pmid: 11328886
references.citation: Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):9160-5
references.pmid: 8799171
references.citation: Free Radic Biol Med. 1998 Nov 15;25(8):891-7
references.pmid: 9840733
references.citation: Arterioscler Thromb Vasc Biol. 2002 May 1;22(5):745-51
references.pmid: 12006385
references.citation: PLoS One. 2015;10(3):e0122439
references.pmid: 25775124
references.citation: Oncogene. 2002 Jul 4;21(29):4558-66
references.pmid: 12085234
references.citation: J Clin Invest. 1997 Nov 1;100(9):2143-5
references.pmid: 9410889
references.citation: Clin Sci (Lond). 1999 Aug;97(2):141-7
references.pmid: 10409468
references.citation: Ann Vasc Surg. 2000 Jul;14(4):385-92
references.pmid: 10943792
references.citation: J Clin Invest. 1995 Nov;96(5):2260-8
references.pmid: 7593612
references.citation: Br J Surg. 1994 Sep;81(9):1254-69
references.pmid: 7953384
references.citation: Br J Cancer. 2014 May 13;110(10):2496-505
references.pmid: 24714752
references.citation: Mol Ther. 2003 Aug;8(2):220-9
references.pmid: 12907144
references.citation: Circ Res. 1997 Jul;81(1):24-33
references.pmid: 9201024
references.citation: Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1137-41
references.pmid: 7532305
references.citation: Science. 1995 Jan 27;267(5197):518-22
references.pmid: 7824950
references.citation: Hypertens Res. 2002 Mar;25(2):249-55
references.pmid: 12047041
references.citation: Circ Res. 1998 Feb 9;82(2):147-56
references.pmid: 9468185
references.citation: Acta Cardiol. 2007 Jun;62(3):281-93
references.pmid: 17608104
references.citation: J Immunol. 2002 Jun 15;168(12):6041-6
references.pmid: 12055212
references.citation: Ann N Y Acad Sci. 2001 Dec;947:271-92; discussion 292-3
references.pmid: 11795276
references.citation: Oncol Rep. 2015 Jan;33(1):193-200
references.pmid: 25371158
references.citation: Circ Res. 1996 Nov;79(5):949-56
references.pmid: 8888687
references.citation: Acta Cardiol. 2000 Aug;55(4):221-32
references.pmid: 11041120
references.citation: Curr Opin Cardiol. 1996 Sep;11(5):457-63
references.pmid: 8889370
references.citation: Int J Mol Med. 2013 Jan;31(1):179-87
references.pmid: 23165955