Os LncRNAs Estão Envolvidos no Processo de Aterosclerose em Diversos Níveis

Liang, Shiyi; Xv, Weicheng; Li, Chijian; Huang, Yuxiang; Qian, Ge; Yan, Yuxiang; Zou, Hequn; Li, Yongqiang

doi:10.36660/abc.20201383

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Artigo de Revisão • Arq. Bras. Cardiol. 118 (6) • 2022 • https://doi.org/10.36660/abc.20201383 copiar

Os LncRNAs Estão Envolvidos no Processo de Aterosclerose em Diversos Níveis

Autoria SCIMAGO INSTITUTIONS RANKINGS

Resumo

A aterosclerose é a causa mais comum de doença cardiovascular em todo o mundo, ela está associada a uma alta incidência de eventos clínicos. O acúmulo de evidências elucidou que os RNAs longos não codificantes (LncRNAs) são uma nova classe de transcritos com papéis críticos nos processos fisiopatológicos da aterosclerose. Nesta revisão, resumimos o progresso recente dos LncRNAs no desenvolvimento da aterosclerose. Descrevemos principalmente os diversos mecanismos regulatórios dos LncRNAs nos níveis transcricionais e pós-transcricionais. Este estudo pode fornecer informações úteis sobre os LncRNAs como alvos terapêuticos ou biomarcadores para o tratamento da aterosclerose.

Palavras-chave
LncRNAs; Enzimas; Inibidores Enzimáticos; Inibidores; Aterosclerose; Doenças Cardiovasculares; Células Endoteliais; Lipoproteínas VLDL; Interferência de RNA

	LncRNAs	Mecanismo	Efeito		Referências
Função celular			Proliferação	Apoptose
Células Endoteliais (ECs)	MALAT1	MALAT1-Pc2 (CBX4)-E2F1	⁺ (+) representa prompt ou aumento, e		³⁸38 Yang L, Lin C, Liu W, Zhang J, Ohgi KA, Grinstein JD, et al. ncRNA- and Pc2 methylation-dependent gene relocation between nuclear structures mediates gene activation programs. Cell. 2011;147(4):773-88. doi: 10.1016/j.cell.2011.08.054. https://doi.org/10.1016/j.cell.2011.08.0...
	GAS5	GAS5 - ceRNA (miR-21)	⁻ (−) representa prevenir ou diminuir.	⁺ (+) representa prompt ou aumento, e	⁷⁵75 Shen Z, She Q. Association Between the Deletion Allele of Ins/Del Polymorphism (Rs145204276) in the Promoter Region of GAS5 with the risk of atherosclerosis. Cell Physiol Biochem. 2018;49(4):1431-43. doi: 10.1159/000493447 https://doi.org/10.1159/000493447...
	HOTTIP	TNF-α/PDGFBB-HOTTIP-β-catenina	⁺ (+) representa prompt ou aumento, e		⁴⁷47 Liao B, Chen R, Lin F, Mai A, Chen J, Li H, et al. Long non-coding RNA HOTTIP promotes endothelial cell proliferation and migration via activation of the Wnt/β-catenin pathway.J Cell Biochem. 2018;19(3):2797-805. doi: 10.1002/jcb.26448. https://doi.org/10.1002/jcb.26448...
	MALAT1	ceRNA (miR-22-3p)		⁻ (−) representa prevenir ou diminuir.	⁶⁰60 Tang Y, Jin X, Xiang Y, Chen Y, Shen CX, Zhang YC, et al. The lncRNA MALAT1 protects the endothelium against ox-LDL-induced dysfunction via upregulating the expression of the miR-22-3p target genes CXCR2 and AKT. FEBS Lett. 2015;589(20Pt8):3189-96. doi: 10.1016/j.febslet.2015.08.046. https://doi.org/10.1016/j.febslet.2015.0...
	TUG1	ceRNA (miR-26a)		⁺ (+) representa prompt ou aumento, e	⁷¹71 Chen C, Cheng G, Yang X, Li C, Shi R, Zhao N. Tanshinol suppresses endothelial cells apoptosis in mice with atherosclerosis via lncRNA TUG1 up-regulating the expression of miR-26a. Am J TRanslat Res.2016;8(7):2981-91. PMID: 27508018
Macrófagos, Células musculares lisas	ANRIL	Ligam com CBX7 e SUZ12	⁺ (+) representa prompt ou aumento, e	⁻ (−) representa prevenir ou diminuir.	³²32 Visel A, Zhu Y, May D, Afzal V, Gong E, Attanasio C, et al. Targeted deletion of the 9p21 non-coding coronary artery disease risk interval in mice. Nature. 2010;464(7287):409-12. doi: 10.1038/nature08801 https://doi.org/10.1038/nature08801...
	NEAT1	NEAT1-WDR5-SM-genes específicos	⁺ (+) representa prompt ou aumento, e		⁴⁴44 ASI Ahmed ASI, Dong K, Liu J, Wen T, Yu L, Xu F, et al. NEAT1Long non-coding RNA (nuclear paraspeckle assembly transcript 1) is critical for phenotypic switching of vascular smooth muscle cells. Proc the Nat Acad Scienc (USA) 2018; 37: E8660-67. doi: 10.3892/mmr.2017.8211 https://doi.org/10.3892/mmr.2017.8211...
	LincRNA-p21	LincRNA-p21-MDM2/ p300-p53	⁺ (+) representa prompt ou aumento, e	⁻ (−) representa prevenir ou diminuir.	⁴⁵45 Wu G, Cai J, Han Y, Chen J, Huang ZP, Chen C, et al. LincRNA-p21 regulates neointima formation, vascular smooth muscle cell proliferation, apoptosis, and atherosclerosis by enhancing p53 activity. Circulation. 2014; 130(17):1452-65. doi: 10.1161/CIRCULATIONAHA.114.011675 https://doi.org/10.1161/CIRCULATIONAHA.1...
	HAS2	remodela estructura da cromatina	⁺ (+) representa prompt ou aumento, e		⁴⁹49 van den Boom M, Sarbia M, von Wnuck Lipinski K, Mann P, Meyer-Kirchrath J, Rauch BH, et al. Differential regulation of hyaluronic acid synthase isoforms in human saphenous vein smooth muscle cells: possible implications for vein graft stenosis. Circ Res.2006;98(1):36-44. doi: 10.1161/01.RES.0000199263.67107.c0. https://doi.org/10.1161/01.RES.000019926... ,⁵⁰50 Viola M, Karousou E, D’Angelo ML, Moretto P, Caon I, Luca G, et al. Extracellular Matrix in Atherosclerosis: Hyaluronan and Proteoglycans Insights. Curr Med Chem. 2016;23(26):2958-71. doi: 10.2174/0929867323666160607104602. https://doi.org/10.2174/0929867323666160...
	RP11-714G18.1	regula positivamente a expressão de LRP2BP		⁻ (−) representa prevenir ou diminuir.	⁵³53 Zhang Y, Zheng L, Xu BM, Tang WH, Ye ZD, Huang C, et al. LncRNA-RP11-714G18.1 suppresses vascular cell migration via directly targeting LRP2BP. Imm cell Biol. 2018; 2:175-89. doi: 10.1016/j.eururo.2018.07.032. https://doi.org/10.1016/j.eururo.2018.07...
	H19	ceRNA (miR-148b)	⁺ (+) representa prompt ou aumento, e	⁻ (−) representa prevenir ou diminuir.	⁶⁶66 Zhang L, Cheng H, Yue Y, Li S, Zhang D,He R. H19 knockdown suppresses proliferation and induces apoptosis by regulating miR-148b/WNT/β-catenin in ox-LDL -stimulated vascular smooth muscle cells. J Biomed Sci.2018;25(1):11.. 2018; 1: 11. doi: 10.1186/s12929-018-0418-4. https://doi.org/10.1186/s12929-018-0418-...
	MIAT	ceRNA (miR-181b)	⁺ (+) representa prompt ou aumento, e	⁻ (−) representa prevenir ou diminuir.	⁶⁹69 Zhong X, Ma X, Zhang L, Li Y, He R. MIAT promotes proliferation and hinders apoptosis by modulating miR-181b/STAT3 axis in ox-LDL-induced atherosclerosis cell models. Biomed Pharmacother Biomed.2018;97: 1078-85. doi: 10.1016/j.biopha.2017.11.052. https://doi.org/10.1016/j.biopha.2017.11...

	LncRNAs	Mecanismo	Efeito	Referências
Acúmulo de Lípidios	MALAT1	captação de lipídios MALAT1-CD36	⁺ (+) representa prompt ou aumento, e	⁴⁵45 Wu G, Cai J, Han Y, Chen J, Huang ZP, Chen C, et al. LincRNA-p21 regulates neointima formation, vascular smooth muscle cell proliferation, apoptosis, and atherosclerosis by enhancing p53 activity. Circulation. 2014; 130(17):1452-65. doi: 10.1161/CIRCULATIONAHA.114.011675 https://doi.org/10.1161/CIRCULATIONAHA.1...
	NEAT1	captação de lipídios NEAT1-CD36	⁻ (−) representa prevenir ou diminuir.	⁴¹41 Huangfu N, Xu Z, Zheng W, Wang Y, Cheng J, Chen X. LncRNA MALAT1 regulates oxLDL-induced CD36 expression via activating β-catenin. Bioch Biopohys Res Comm. 2018;3:2111-7. (ISSN: 1090-2104)
	MeXis	LXR-MeXis-Abca1	⁻ (−) representa prevenir ou diminuir.	⁴⁶46 Sallam T, Jones M, Thomas BJ, Wu X, Gilliland T, Qian K, et al. Transcriptional regulation of macrophage cholesterol efflux and atherogenesis by a long non-coding RNA. Nat Med. 2018;24(3):304-12. doi: 10.1038/nm.4479. https://doi.org/10.1038/nm.4479...
	H19	ceRNA (miR-130b)	⁻ (−) representa prevenir ou diminuir.	⁶⁵65 Han Y, Ma J, Wang J, Wang L Silencing of H19 inhibits the adipogenesis and inflammation response in ox-LDL-treated Raw264.7 cells by up-regulating miR-130b. Mol Immunol.2018;93:107-14. doi: 10.1016/j.molimm.2017.11.017 https://doi.org/10.1016/j.molimm.2017.11...
	TUG1	ceRNA (miR-133a)	⁺ (+) representa prompt ou aumento, e	⁷²72 Zhang L, Cheng H, Yue Y, Li S, Zhang D, He R. TUG1 knockdown ameliorates atherosclerosis via up-regulating the expression of miR-133a target gene FGF1. Cardiovasc Pathol. 2018;33: 6-15. doi: 10.1016/j.carpath.2017.11.004. https://doi.org/10.1016/j.carpath.2017.1...

	LncRNAs	Mecanismo	Efeito	Referências
Resposta inflamatória	ANRIL	TNF-α/NF-kB-ANRIL/YY1-IL6/8	⁺ (+) representa prompt ou aumento, e	³⁴34 Zhou X, Han X, Wittfeldt A, Sun J, Liu C, Wang X, et al. Long non-coding RNA ANRIL regulates inflammatory responses as a novel component of NF-κB pathway. RNA Biol. 2016;1(1):98-108. doi: 10.3892/mmr.2020.11203 https://doi.org/10.3892/mmr.2020.11203...
	MALAT1	MALAT1-p65/p50-TNF-α e IL-6	⁻ (−) representa prevenir ou diminuir.	⁴⁰40 Zhao G, Su Z, Song D, Mao Y, Mao X. The long non-coding RNA MALAT1 regulates the lipopolysaccharide-induced inflammatory response through its interaction with NF-κB. FEBS Lett. 2016;590(17): 2884-95. doi: 10.1002/1873-3468.12315 https://doi.org/10.1002/1873-3468.12315...
	MALAT1	ceRNA (miR-503 or miR-155)	⁻ (−) representa prevenir ou diminuir.	⁶¹61 Cremer S, Michalik KM, Fischer A,Jae N, Winter C. Hematopoietic Deficiency of the Long Non-coding RNA MALAT1 Promotes Atherosclerosis and Plaque Inflammation. Circulation. 2019;139(10):1320-34. doi: 10.1016/j.febslet.2015.08.046. https://doi.org/10.1016/j.febslet.2015.0... ,⁶²62 Li S, Sun Y, Zhong L, Xiao Z, Yang M, Chen M, et al. The suppression of ox-LDL-induced inflammatory cytokine release and apoptosis of HCAECs by long non-coding RNA-MALAT1 via regulating microRNA-155/SOCS1 pathway. Nutr Metabol Cardiovasc Dis. 2018; 28(11): 1175-87. . doi: 10.1016/j.numecd.2018.06.017. https://doi.org/10.1016/j.numecd.2018.06...
	H19	ceRNA (miR-130b)	⁻ (−) representa prevenir ou diminuir.
	NEAT1	ceRNA (miR-342-3p)	⁺ (+) representa prompt ou aumento, e	⁷⁰70 Wang L, Xia JW, Ke ZP, Zhang H. Blockade of NEAT1 represses inflammation response and lipid uptake via modulating miR-342-3p in human macrophages THP-1 cells. J Cell Physiol.2019;234(4): 5319-26. doi: 10.1002/jcp.27340. https://doi.org/10.1002/jcp.27340...
	TUG1	ceRNA (miR-133a)	⁺ (+) representa prompt ou aumento, e	⁷²72 Zhang L, Cheng H, Yue Y, Li S, Zhang D, He R. TUG1 knockdown ameliorates atherosclerosis via up-regulating the expression of miR-133a target gene FGF1. Cardiovasc Pathol. 2018;33: 6-15. doi: 10.1016/j.carpath.2017.11.004. https://doi.org/10.1016/j.carpath.2017.1...

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[1] Correspondência: Yongqiang Li • The Third Affiliated Hospital of Southern Medical University – GuangDong GuangZhou 510000 – China. E-mail: liyongqiang851@163.com