Mechanism of lncRNA H19 regulating miR-214/Caspase-1 axis involved in chronic heart failure in rats_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

ZHANG Yirong ^1,2 , DENG Yonglan ¹ , TANG Yifeng ² , LI Yongjun ² , LIU Li ² ,  YANG Lin ¹

1. Department of Human Anatomy, Zhuhai Campus of Zunyi Medical University, Zhuhai, 519090, Guangdong, P. R. China;
2. Department of Cardiology, The People's Hospital of Liupanshui City, Liupanshui, 553001, Guizhou, P. R. China;

Corresponding author：

YANG Lin, Email: aiyzwll@aliyun.com

Keywords：

Long non-coding RNA H19; microRNA-214; chronic heart failure; cysteinyl aspartate specific proteinase-1; myocardial injury

DOI：

10.7507/1007-4848.202203001

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Objective To explore the effect of long non-coding RNA H19 (lncRNA H19) on chronic heart failure (CHF) rats and its possible mechanism. Methods CHF (SD male rats, with a weight of 300±10 g, 10 weeks old) rat model was established by abdominal aortic coarctation. The 84 rats successfully modeled were randomly divided into a model group, a si-NC group [transfected lncRNA H19 small interfering RNA (siRNA) negative control], a si-H19 group (transfected lncRNA H19 siRNA), a si-miR-NC group [transfected microRNA-214 (miR-214) siRNA negative control], a si-miR-214 group (transfected miR-214 siRNA), a si-H19+si-miR-NC group (co-transfected lncRNA H19 siRNA and miR-214 siRNA negative control), and a si-H19+si-miR-214 group (co-transfected lncRNA H19 siRNA and miR-214 siRNA), 12 rats in each group. Another 12 rats were set up in a sham operation group (rats were only threaded without ligation, and the other operations were the same as the model group). After 4 weeks of intervention, the cardiac function, serum myocardial injury markers, heart failure markers, inflammatory related factors, apoptosis related factors and myocardial histopathological changes were compared. The expressions of lncRNA H19 and miR-214 in myocardial tissue were detected by real-time fluorescence quantitative PCR, and the targeting relationship between lncRNA H19 and miR-214 was detected by double luciferase reporter gene. Results Compared with those in the sham operation group, the myocardium of rats in the model group was severely damaged and a large number of inflammatory cells infiltrated; the lncRNA H19, cardiac function indexes (left ventricular end systolic diameter, left ventricular end diastolic diameter), serum myocardial injury markers (creatine kinase MB, cardiac troponin I), heart failure markers (brain natriuretic peptide, N-terminal pro brain natriuretic peptide), inflammatory related factors (interleukin-1β, interleukin-18, tumor necrosis factor-α, interleukin-6), cardiomyocyte apoptosis rate, apoptosis related proteins [B lymphocytoma-2 (Bcl-2), Bcl-2 related X protein (Bax), cysteinyl aspartate specific proteinase-1 (Caspase-1)] in the myocardial tissue of the model group were significantly increased (P<0.05); miR-214 of myocardial tissue, cardiac function indexes (left ventricular ejection fraction, left ventricular fractional shortening) and Bcl-2/Bax ratio were significantly decreased (P<0.05). Compared with the model group, silencing lncRNA H19 could significantly improve the cardiac function and the changes of the above indexes in CHF rats, and reduce myocardial injury (P<0.05); down-regulation of miR-214 could significantly reverse the protective effect of si-H19 on myocardial injury in CHF rats (P<0.05). Conclusion Silencing lncRNA H19 can up-regulate the expression of miR-214, inhibit the expression of Caspase-1, inhibit the apoptosis and inflammatory reaction of cardiomyocytes, and alleviate myocardial injury in rats with CHF.

Citation： ZHANG Yirong, DENG Yonglan, TANG Yifeng, LI Yongjun, LIU Li, YANG Lin. Mechanism of lncRNA H19 regulating miR-214/Caspase-1 axis involved in chronic heart failure in rats. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2023, 30(11): 1628-1637. doi: 10.7507/1007-4848.202203001 Copy

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2.	中国康复医学会心血管病预防与康复专业委员会. 慢性心力衰竭心脏康复中国专家共识. 中华内科杂志, 2020, 59(12): 942-952.
3.	Ptaszynska-Kopczynska K, Sawicka E, Marcinkiewicz-Siemion M, et al. Chemokines profile in patients with chronic heart failure treated with cardiac resynchronization therapy. Adv Med Sci, 2020, 65(1): 102-110.
4.	Lopez PD, Cativo-Calderon EH, Otero D, et al. The impact of environmental factors on the mortality of patients with chronic heart failure. Am J Cardiol, 2021, 146: 48-55.
5.	Emrich T, Hahn F, Fleischmann D, et al. T1 and T2 mapping to detect chronic inflammation in cardiac magnetic resonance imaging in heart failure with reduced ejection fraction. ESC Heart Fail, 2020, 7(5): 2544-2552.
6.	Song J, Kim YK. Discovery and functional prediction of long non-coding RNAs common to ischemic stroke and myocardial infarction. J Lipid Atheroscler, 2020, 9(3): 449-459.
7.	Hobuß L, Foinquinos A, Jung M, et al. Pleiotropic cardiac functions controlled by ischemia-induced lncRNA H19. J Mol Cell Cardiol, 2020, 146: 43-59.
8.	Omura J, Habbout K, Shimauchi T, et al. Identification of long noncoding RNA H19 as a new biomarker and therapeutic target in right ventricular failure in pulmonary arterial hypertension. Circulation, 2020, 142(15): 1464-1484.
9.	Shirazi-Tehrani E, Firouzabadi N, Tamaddon G, et al. Carvedilol alters circulating MiR-1 and MiR-214 in heart failure. Pharmgenomics Pers Med, 2020, 13: 375-383.
10.	杨曦艳, 关晓楠, 赵文淑, 等. miR-214-5p靶向PAK4对缺血再灌注大鼠的心肌损伤和免疫反应的调节作用. 中国病理生理杂志, 2020, 36(3): 394-400.
11.	许红芳. 曲美他嗪对慢性心力衰竭大鼠心功能的影响. 中国临床药理学杂志, 2020, 36(10): 1237-1239.
12.	马静雅, 时潇丽, 刘力. 鹿角方中10种成分在慢性心力衰竭大鼠左右肾脏中的组织分布. 中成药, 2020, 42(8): 1965-1971.
13.	Kiefer KC, Cremer S, Pardali E, et al. Full spectrum of clonal haematopoiesis-driver mutations in chronic heart failure and their associations with mortality. ESC Heart Fail, 2021, 8(3): 1873-1884.
14.	Das S, Shah R, Dimmeler S, et al. Noncoding RNAs in cardiovascular disease: Current knowledge, tools and technologies for investigation, and future directions: A scientific statement from the American Heart Association. Circ Genom Precis Med, 2020, 13(4): e000062.
15.	Zhang BF, Jiang H, Chen J, et al. LncRNA H19 ameliorates myocardial infarction-induced myocardial injury and maladaptive cardiac remodelling by regulating KDM3A. J Cell Mol Med, 2020, 24(1): 1099-1115.
16.	Sweeney C, Pharithi RB, Kerr B, et al. NT-proBNP/BNP ratio for prognostication in European Caucasian patients enrolled in a heart failure prevention programme. ESC Heart Fail, 2021, 8(6): 5081-5091.
17.	Chaar D, Dumont B, Vulesevic B, et al. Neutrophils pro-inflammatory and anti-inflammatory cytokine release in patients with heart failure and reduced ejection fraction. ESC Heart Fail, 2021, 8(5): 3855-3864.
18.	Wu J, Dong E, Zhang Y, et al. The role of the inflammasome in heart failure. Front Physiol, 2021, 12: 709703.
19.	Abbate A, Toldo S, Marchetti C, et al. Interleukin-1 and the inflammasome as therapeutic targets in cardiovascular disease. Circ Res, 2020, 126(9): 1260-1280.
20.	Yu BY, Dong B. LncRNA H19 regulates cardiomyocyte apoptosis and acute myocardial infarction by targeting miR-29b. Int J Cardiol, 2018, 271: 25.
21.	瞿奥林, 郭任维, 马明峰, 等. 中性粒细胞与淋巴细胞比值联合NT-proBNP评估慢性心力衰竭患者的短期预后价值. 中国临床研究, 2019, 32(12): 1632-1635.
22.	Wang Q, Wu J, Zeng Y, et al. Pyroptosis: A pro-inflammatory type of cell death in cardiovascular disease. Clin Chim Acta, 2020, 510: 62-72.
23.	Chen Z, Zhang Y, Lin R, et al. Cronobacter sakazakii induces necrotizing enterocolitis by regulating NLRP3 inflammasome expression via TLR4. J Med Microbiol, 2020, 69(5): 748-758.
24.	Zhu YF, Wang R, Chen W, et al. miR-133a-3p attenuates cardiomyocyte hypertrophy through inhibiting pyroptosis activation by targeting IKKε. Acta Histochem, 2021, 123(1): 151653.
25.	Yang F, Li A, Qin Y, et al. A novel circular RNA mediates pyroptosis of diabetic cardiomyopathy by functioning as a competing endogenous RNA. Mol Ther Nucleic Acids, 2019, 17: 636-643.
26.	Yang F, Qin Y, Wang Y, et al. LncRNA KCNQ1OT1 mediates pyroptosis in diabetic cardiomyopathy. Cell Physiol Biochem, 2018, 50(4): 1230-1244.

1. Sze S, Pellicori P, Zhang J, et al. Effect of frailty on treatment, hospitalisation and death in patients with chronic heart failure. Clin Res Cardiol, 2021, 110(8): 1249-1258.
2. 中国康复医学会心血管病预防与康复专业委员会. 慢性心力衰竭心脏康复中国专家共识. 中华内科杂志, 2020, 59(12): 942-952.
3. Ptaszynska-Kopczynska K, Sawicka E, Marcinkiewicz-Siemion M, et al. Chemokines profile in patients with chronic heart failure treated with cardiac resynchronization therapy. Adv Med Sci, 2020, 65(1): 102-110.
4. Lopez PD, Cativo-Calderon EH, Otero D, et al. The impact of environmental factors on the mortality of patients with chronic heart failure. Am J Cardiol, 2021, 146: 48-55.
5. Emrich T, Hahn F, Fleischmann D, et al. T1 and T2 mapping to detect chronic inflammation in cardiac magnetic resonance imaging in heart failure with reduced ejection fraction. ESC Heart Fail, 2020, 7(5): 2544-2552.
6. Song J, Kim YK. Discovery and functional prediction of long non-coding RNAs common to ischemic stroke and myocardial infarction. J Lipid Atheroscler, 2020, 9(3): 449-459.
7. Hobuß L, Foinquinos A, Jung M, et al. Pleiotropic cardiac functions controlled by ischemia-induced lncRNA H19. J Mol Cell Cardiol, 2020, 146: 43-59.
8. Omura J, Habbout K, Shimauchi T, et al. Identification of long noncoding RNA H19 as a new biomarker and therapeutic target in right ventricular failure in pulmonary arterial hypertension. Circulation, 2020, 142(15): 1464-1484.
9. Shirazi-Tehrani E, Firouzabadi N, Tamaddon G, et al. Carvedilol alters circulating MiR-1 and MiR-214 in heart failure. Pharmgenomics Pers Med, 2020, 13: 375-383.
10. 杨曦艳, 关晓楠, 赵文淑, 等. miR-214-5p靶向PAK4对缺血再灌注大鼠的心肌损伤和免疫反应的调节作用. 中国病理生理杂志, 2020, 36(3): 394-400.
11. 许红芳. 曲美他嗪对慢性心力衰竭大鼠心功能的影响. 中国临床药理学杂志, 2020, 36(10): 1237-1239.
12. 马静雅, 时潇丽, 刘力. 鹿角方中10种成分在慢性心力衰竭大鼠左右肾脏中的组织分布. 中成药, 2020, 42(8): 1965-1971.
13. Kiefer KC, Cremer S, Pardali E, et al. Full spectrum of clonal haematopoiesis-driver mutations in chronic heart failure and their associations with mortality. ESC Heart Fail, 2021, 8(3): 1873-1884.
14. Das S, Shah R, Dimmeler S, et al. Noncoding RNAs in cardiovascular disease: Current knowledge, tools and technologies for investigation, and future directions: A scientific statement from the American Heart Association. Circ Genom Precis Med, 2020, 13(4): e000062.
15. Zhang BF, Jiang H, Chen J, et al. LncRNA H19 ameliorates myocardial infarction-induced myocardial injury and maladaptive cardiac remodelling by regulating KDM3A. J Cell Mol Med, 2020, 24(1): 1099-1115.
16. Sweeney C, Pharithi RB, Kerr B, et al. NT-proBNP/BNP ratio for prognostication in European Caucasian patients enrolled in a heart failure prevention programme. ESC Heart Fail, 2021, 8(6): 5081-5091.
17. Chaar D, Dumont B, Vulesevic B, et al. Neutrophils pro-inflammatory and anti-inflammatory cytokine release in patients with heart failure and reduced ejection fraction. ESC Heart Fail, 2021, 8(5): 3855-3864.
18. Wu J, Dong E, Zhang Y, et al. The role of the inflammasome in heart failure. Front Physiol, 2021, 12: 709703.
19. Abbate A, Toldo S, Marchetti C, et al. Interleukin-1 and the inflammasome as therapeutic targets in cardiovascular disease. Circ Res, 2020, 126(9): 1260-1280.
20. Yu BY, Dong B. LncRNA H19 regulates cardiomyocyte apoptosis and acute myocardial infarction by targeting miR-29b. Int J Cardiol, 2018, 271: 25.
21. 瞿奥林, 郭任维, 马明峰, 等. 中性粒细胞与淋巴细胞比值联合NT-proBNP评估慢性心力衰竭患者的短期预后价值. 中国临床研究, 2019, 32(12): 1632-1635.
22. Wang Q, Wu J, Zeng Y, et al. Pyroptosis: A pro-inflammatory type of cell death in cardiovascular disease. Clin Chim Acta, 2020, 510: 62-72.
23. Chen Z, Zhang Y, Lin R, et al. Cronobacter sakazakii induces necrotizing enterocolitis by regulating NLRP3 inflammasome expression via TLR4. J Med Microbiol, 2020, 69(5): 748-758.
24. Zhu YF, Wang R, Chen W, et al. miR-133a-3p attenuates cardiomyocyte hypertrophy through inhibiting pyroptosis activation by targeting IKKε. Acta Histochem, 2021, 123(1): 151653.
25. Yang F, Li A, Qin Y, et al. A novel circular RNA mediates pyroptosis of diabetic cardiomyopathy by functioning as a competing endogenous RNA. Mol Ther Nucleic Acids, 2019, 17: 636-643.
26. Yang F, Qin Y, Wang Y, et al. LncRNA KCNQ1OT1 mediates pyroptosis in diabetic cardiomyopathy. Cell Physiol Biochem, 2018, 50(4): 1230-1244.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Mechanism of lncRNA H19 regulating miR-214/Caspase-1 axis involved in chronic heart failure in rats

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