دورية أكاديمية
أعرض في EDS

Inhibition of Slc39a14/Slc39a8 reduce vascular calcification via alleviating iron overload induced ferroptosis in vascular smooth muscle cells.

التفاصيل البيبلوغرافية
العنوان: Inhibition of Slc39a14/Slc39a8 reduce vascular calcification via alleviating iron overload induced ferroptosis in vascular smooth muscle cells.
المؤلفون: Aierken Y; Department of Vascular Surgery, The Affiliated Hospital, Southwest Medical University, No. 25, Taiping Street, Luzhou, 646000, Sichuan, China., He H; Department of Vascular Surgery, The Affiliated Hospital, Southwest Medical University, No. 25, Taiping Street, Luzhou, 646000, Sichuan, China.; Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, (Collaborative Innovation Center for Prevention of Cardiovascular Diseases) Institute of Cardiovascular Research, Southwest Medical University, Luzhou, 646000, China.; Department of General Surgery, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China., Li R; Department of Vascular Surgery, The Affiliated Hospital, Southwest Medical University, No. 25, Taiping Street, Luzhou, 646000, Sichuan, China., Lin Z; Department of Vascular Surgery, The Affiliated Hospital, Southwest Medical University, No. 25, Taiping Street, Luzhou, 646000, Sichuan, China., Xu T; Department of Vascular Surgery, The Affiliated Hospital, Southwest Medical University, No. 25, Taiping Street, Luzhou, 646000, Sichuan, China., Zhang L; Department of Vascular Surgery, The Affiliated Hospital, Southwest Medical University, No. 25, Taiping Street, Luzhou, 646000, Sichuan, China., Wu Y; Department of Vascular Surgery, The Affiliated Hospital, Southwest Medical University, No. 25, Taiping Street, Luzhou, 646000, Sichuan, China. yawu@swmu.du.cn.; Metabolic Vascular Disease Key Laboratory of Sichuan Province, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China. yawu@swmu.du.cn., Liu Y; Department of Vascular Surgery, The Affiliated Hospital, Southwest Medical University, No. 25, Taiping Street, Luzhou, 646000, Sichuan, China. lyong74@swmu.edu.cn.; Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, (Collaborative Innovation Center for Prevention of Cardiovascular Diseases) Institute of Cardiovascular Research, Southwest Medical University, Luzhou, 646000, China. lyong74@swmu.edu.cn.; Department of General Surgery, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China. lyong74@swmu.edu.cn.; Metabolic Vascular Disease Key Laboratory of Sichuan Province, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China. lyong74@swmu.edu.cn.
المصدر: Cardiovascular diabetology [Cardiovasc Diabetol] 2024 May 29; Vol. 23 (1), pp. 186. Date of Electronic Publication: 2024 May 29.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101147637 Publication Model: Electronic Cited Medium: Internet ISSN: 1475-2840 (Electronic) Linking ISSN: 14752840 NLM ISO Abbreviation: Cardiovasc Diabetol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : BioMed Central, [2002-
مواضيع طبية MeSH: Ferroptosis*/drug effects , Vascular Calcification*/metabolism , Vascular Calcification*/pathology , Cation Transport Proteins*/metabolism , Cation Transport Proteins*/genetics , Myocytes, Smooth Muscle*/metabolism , Myocytes, Smooth Muscle*/drug effects , Myocytes, Smooth Muscle*/pathology , Disease Models, Animal* , Muscle, Smooth, Vascular*/pathology , Muscle, Smooth, Vascular*/metabolism , Muscle, Smooth, Vascular*/drug effects , Mice, Inbred C57BL* , Iron Chelating Agents*/pharmacology , Iron Chelating Agents*/therapeutic use, Animals ; Signal Transduction ; Male ; Humans ; Iron/metabolism ; Iron Overload/metabolism ; Iron Overload/pathology
مستخلص: Background: Vascular calcification (VC) is an independent risk factor for cardiovascular diseases. Recently, ferroptosis has been recognised as a novel therapeutic target for cardiovascular diseases. Although an association between ferroptosis and vascular calcification has been reported, the role and mechanism of iron overload in vascular calcification are still poorly understood. Specifically, further in-depth research is required on whether metalloproteins SLC39a14 and SLC39a8 are involved in ferroptosis induced by iron overload.
Methods: R language was employed for the differential analysis of the dataset, revealing the correlation between ferroptosis and calcification. The experimental approaches encompassed both in vitro and in vivo studies, incorporating the use of iron chelators and models of iron overload. Additionally, gain- and loss-of-function experiments were conducted to investigate iron's effects on vascular calcification comprehensively. Electron microscopy, immunofluorescence, western blotting, and real-time polymerase chain reaction were used to elucidate how Slc39a14 and Slc39a8 mediate iron overload and promote calcification.
Results: Ferroptosis was observed in conjunction with vascular calcification (VC); the association was consistently confirmed by in vitro and in vivo studies. Our results showed a positive correlation between iron overload in VSMCs and calcification. Iron chelators are effective in reversing VC and iron overload exacerbates this process. The expression levels of the metal transport proteins Slc39a14 and Slc39a8 were significantly upregulated during calcification; the inhibition of their expression alleviated VC. Conversely, Slc39a14 overexpression exacerbates calcification and promotes intracellular iron accumulation in VSMCs.
Conclusions: Our research demonstrates that iron overload occurs during VC, and that inhibition of Slc39a14 and Slc39a8 significantly relieves VC by intercepting iron overload-induced ferroptosis in VSMCs, providing new insights into the VC treatment.
(© 2024. The Author(s).)
References: J Nutr. 2018 Feb 1;148(2):174-184. (PMID: 29490098)
Eur Heart J. 2015 Dec 21;36(48):3381-3. (PMID: 26690751)
Trends Cardiovasc Med. 2012 May;22(4):93-8. (PMID: 23040839)
Nephrol Dial Transplant. 2003 Sep;18(9):1731-40. (PMID: 12937218)
Int J Mol Sci. 2022 Nov 17;23(22):. (PMID: 36430673)
Pharmacol Ther. 2015 Feb;146:35-52. (PMID: 25205158)
Cell Metab. 2015 Jul 7;22(1):138-50. (PMID: 26028554)
Int J Mol Sci. 2021 Jul 22;22(15):. (PMID: 34360586)
Annu Rev Med. 2023 Jan 27;74:261-277. (PMID: 35905974)
Kidney Int. 2022 Dec;102(6):1259-1275. (PMID: 36063875)
J Exp Med. 2002 Oct 21;196(8):1047-55. (PMID: 12391016)
Bone. 2018 Apr;109:28-34. (PMID: 28688892)
Eur Heart J. 2020 Jul 21;41(28):2681-2695. (PMID: 30903157)
Nat Commun. 2014 Oct 29;5:4926. (PMID: 25352340)
Cell. 2012 May 25;149(5):1060-72. (PMID: 22632970)
Int J Mol Sci. 2019 Nov 25;20(23):. (PMID: 31775364)
Theranostics. 2021 Jan 1;11(7):3052-3059. (PMID: 33537073)
Hum Genomics. 2019 Sep 14;13(Suppl 1):51. (PMID: 31521203)
Nat Rev Cardiol. 2023 Jan;20(1):7-23. (PMID: 35788564)
J Biol Chem. 2023 Aug;299(8):105078. (PMID: 37482277)
Cell Death Dis. 2022 May 18;13(5):467. (PMID: 35585052)
Nature. 2014 May 1;509(7498):105-9. (PMID: 24695223)
Trends Endocrinol Metab. 2021 Jul;32(7):444-462. (PMID: 34006412)
Dtsch Arztebl Int. 2021 Dec 10;118(49):847-856. (PMID: 34755596)
Circ Res. 2015 May 22;116(11):1783-99. (PMID: 25999419)
Blood Adv. 2023 Apr 11;7(7):1336-1349. (PMID: 36260707)
Cell. 2017 Jan 26;168(3):344-361. (PMID: 28129536)
Arterioscler Thromb Vasc Biol. 2019 Jul;39(7):1307-1316. (PMID: 31144990)
Biochem Pharmacol. 2023 Feb;208:115379. (PMID: 36525991)
J Inherit Metab Dis. 2017 Jul;40(4):519-529. (PMID: 28303424)
Free Radic Biol Med. 2024 Mar;214:42-53. (PMID: 38309537)
J Colloid Interface Sci. 2018 Oct 15;528:145-155. (PMID: 29843062)
Atherosclerosis. 2021 May;324:117-120. (PMID: 33832772)
Toxicol Appl Pharmacol. 2009 Aug 1;238(3):250-7. (PMID: 19265717)
Arterioscler Thromb Vasc Biol. 2020 May;40(5):1078-1093. (PMID: 32237904)
Trends Biochem Sci. 2016 Mar;41(3):274-286. (PMID: 26725301)
Free Radic Biol Med. 2019 Mar;133:55-63. (PMID: 30055235)
Signal Transduct Target Ther. 2022 Aug 15;7(1):288. (PMID: 35970840)
Environ Toxicol. 2024 Jan;39(1):199-211. (PMID: 37688783)
Free Radic Biol Med. 2011 Sep 1;51(5):978-92. (PMID: 21627987)
Biometals. 2019 Apr;32(2):211-226. (PMID: 30806852)
Circulation. 2021 Mar 16;143(11):1157-1172. (PMID: 33720773)
Mol Aspects Med. 2020 Oct;75:100906. (PMID: 32977976)
Arterioscler Thromb Vasc Biol. 2014 Nov;34(11):2495-500. (PMID: 25169933)
Biometals. 2023 Feb;36(1):227-237. (PMID: 36454509)
Atherosclerosis. 2016 Nov;254:93-101. (PMID: 27716569)
Nephrol Dial Transplant. 2016 Oct;31(10):1588-94. (PMID: 26142396)
Front Cell Dev Biol. 2021 Dec 16;9:809457. (PMID: 34977044)
Nutrients. 2023 Jan 23;15(3):. (PMID: 36771298)
J Cell Physiol. 2021 Jul;236(7):4888-4901. (PMID: 33372284)
J Clin Invest. 2018 Jul 2;128(7):3024-3040. (PMID: 29889103)
Antioxidants (Basel). 2023 Jan 31;12(2):. (PMID: 36829885)
Bioresour Technol. 2021 Oct;337:125390. (PMID: 34126359)
Free Radic Biol Med. 2017 Jul;108:610-626. (PMID: 28433662)
Cardiovasc Res. 2018 Mar 15;114(4):590-600. (PMID: 29514202)
Cell Death Differ. 2018 Mar;25(3):486-541. (PMID: 29362479)
Glia. 2020 Sep;68(9):1810-1823. (PMID: 32077535)
Life Sci. 2024 Mar 1;340:122370. (PMID: 38141854)
Proc Natl Acad Sci U S A. 2019 Feb 12;116(7):2672-2680. (PMID: 30692261)
Eur J Vasc Endovasc Surg. 2018 Mar;55(3):425-432. (PMID: 29371036)
Free Radic Biol Med. 2022 May 1;184:158-169. (PMID: 35331838)
Biomolecules. 2022 Nov 18;12(11):. (PMID: 36421722)
معلومات مُعتمدة: 2023LZXNYDJ043 the Luzhou-Southwest Medical University cooperation project; 2023LZXNYDT013 the Luzhou-Southwest Medical University cooperation project; 2021LZXNYD-D11 the Luzhou-Southwest Medical University cooperation project; 82200432 National Natural Science Foundation of China; 2022NSFSC1448 the Natural Science Foundation of Sichuan Province of China; S23010 the Foundation of Sichuan Provincial Medical Association; KeyME-2022-08 the Key Laboratory of Medical Electrophysiology (Southwest Medical University)
فهرسة مساهمة: Keywords: Ferroptosis; Iron overload; Iron transport; Oxidative stress; Vascular calcification
المشرفين على المادة: 0 (Cation Transport Proteins)
0 (Iron Chelating Agents)
0 (SLC39A14 protein, mouse)
E1UOL152H7 (Iron)
0 (SLC39A8 protein, human)
0 (SLC39A14 protein, human)
تواريخ الأحداث: Date Created: 20240529 Date Completed: 20240530 Latest Revision: 20240606
رمز التحديث: 20240606
مُعرف محوري في PubMed: PMC11138056
DOI: 10.1186/s12933-024-02224-z
PMID: 38812011
قاعدة البيانات: MEDLINE
الوصف
تدمد:1475-2840
DOI:10.1186/s12933-024-02224-z