Issue
Effect of trimetazidine combined with perindopril on NT-proBNP level in rats with dilated cardiomyopathy
Corresponding Author(s) : Bin Zhong
Cellular and Molecular Biology,
Vol. 66 No. 2: Issue 2
Abstract
This experiment aimed to study the effect of trimetazidine combined with perindopril on NT-proBNP levels in rats with dilated cardiomyopathy (DCM). 40 SD rats were selected and 10 rats were randomly selected to continue to be fed as the blank group. The other 30 rats were injected with adriamycin to establish the DCM rat model. Then they were divided into 3 groups, namely control group (without any drug intervention), trimetazidine group (with trimetazidine single-agent intervention) and combination drug group (with trimetazidine combined with perindopril intervention), with 10 DCM rats in each group. After 4 weeks of intervention, left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD) and left ventricular end-systolic diameter (LVESD) of rats were measured by echocardiography. The changes of plasma brain natriuretic peptide (BNP) level and n-terminal pro-brain natriuretic peptide (NT-proBNP) were detected by ELISA. RT-PCR was used to detect the regulation of angiotensin II type 1 receptor (AT1Rs) and lamin A mRNA expression in rat myocardium. After the intervention, the LVEF%, LVEDD and LVESD measured values of the rats in the combination drug group were significantly better than those in the trimetazidine group and the control group (P< 0.05). The BNP, NT-proBNP and AT1Rs levels of the rats in the combination drug group were significantly lower than those in the trimetazidine group and the control group. The difference was statistically significant (p< 0.05). The lamin A expression of the rats in the combination drug group was significantly higher than that in the trimetazidine group and the control group. The difference was statistically significant (P< 0.05). Compared with trimetazidine single-agent, trimetazidine combined with perindopril can significantly improve the cardiac function of rats with dilated cardiomyopathy, reduce the serum NT-proBNP level and improve the expression of AT1Rs and lamin A in rats.
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- Weintraub RG, Semsarian C and Macdonald P: Dilated cardiomyopathy. Lancet 2017; 390: 400-414.
- Merlo M, Cannatí A, Gobbo M, Stolfo D, Elliott PM, Sinagra G. Evolving concepts in dilated cardiomyopathy. Eur J Heart Fail 2018; 20: 228-239.
- Hershberger RE, Hedges DJ and Morales A. The complexity of a diverse genetic architecture. Nat Rev Cardiol 2013; 10: 531-547.
- Das S, Biswas A, Kapoor M, Seth S, Bhargava B, Rao VR. Epidemiology of cardiomyopathy–A clinical and genetic study of dilated cardiomyopathy: The EPOCH-D study. J Pract Cardiovasc Sci 2015; 1;1:30.
- Lakdawala NK, Winterfield JR, Funke BH. Dilated cardiomyopathy. Circ Arrhythm Electrophysiol 2013; 6: 228-237.
- Liang Y, Lin Q, Huang P, Wang Y, Li J, Zhang L and Cao J: Rice Bioactive Peptide Binding with TLR4 To Overcome H2O2-Induced Injury in Human Umbilical Vein Endothelial Cells through NF-κB Signaling. J Agri Food Chem 2018; 66(2): 440-448.
- Wang L, Lin Q, Yang T, Liang Y, Nie Y, Luo Y and Luo F: Oryzanol modifies high fat diet-induced obesity, liver gene expression profile, and inflammation response in mice. J Agri Food Chem 2017; 65(38): 8374-8385.
- Lou Y, Shi J, Guo D, Qureshi AK and Song L: Function of PD-L1 in antitumor immunity of glioma cells. Saudi J Boil Sci 2017; 24(4): 803-807.
- Guo T, Lin Q, Li X, Nie Y, Wang L, Shi L and Luo F: Octacosanol attenuates inflammation in both RAW264. 7 macrophages and a mouse model of colitis. J Agri Food Chem 2017; 65(18): 3647-3658.
- Li W, Jia MX, Wang JH, Lu JL, Deng J, Tang JX and Liu C: Association of MMP9-1562C/T and MMP13-77A/G polymorphisms with non-small cell lung cancer in southern Chinese population. Biomol 2019; 9(3): 107-119.
- McNally EM, Golbus JR, Puckelwartz MJ. Genetic mutations and mechanisms in dilated cardiomyopathy. J Clin Invest 2013; 123: 19-26.
- Bera M, Kumar R, Sinha B, Sengupta K. Nuclear deformation and anchorage defect induced by DCM mutants in lamin A. bioRxiv 2019; 1:611665.
- Van Rijsingen IA, Arbustini E, Elliott PM, Mogensen J, Hermans-van Ast JF, Van Der Kooi AJ, Van Tintelen JP, Van Den Berg MP, Pilotto A, Pasotti M, Jenkins S. Risk factors for malignant ventricular arrhythmias in lamin A/C mutation carriers: a European cohort study. J Am Coll Cardiol 2012; 31;59(5):493-500.
- Mathew T, Williams L, Navaratnam G, Rana B, Wheeler R, Collins K, Harkness A, Jones R, Knight D, O'Gallagher K, Oxborough D. Diagnosis and assessment of dilated cardiomyopathy:aguideline protocol from the British Society of Echocardiography. Echo Res Pract 2017; 4: G1-G13.
- Madamanchi C, Alhosaini H, Sumida A and Runge MS. Obesity and natriuretic peptides, BNP and NT-proBNP: mechanisms and diagnostic implications for heart failure. Int J Cardiol 2014; 176: 611-617.
- Koura HM, Abdalla NM, Hamed Ibrahim M, Abo Hashish MM and Zaki SM. NT-proBNP in children with left to right shunt and dilated cardiomyopathy. Iran J Pediatr 2016; 26: e4485.
- von Lueder TG, Sangaralingham SJ, Wang BH, Kompa AR, Atar D, Burnett JC Jr, Krum H. Renin-angiotensin blockade combined with natriuretic peptide system augmentation: novel therapeutic concepts to combat heart failure. Circ Heart Fail 2013; 6: 594-605.
- Vardeny O, Tacheny T, Solomon SD. First-in-class angiotensin receptor neprilysin inhibitor in heart failure. Clin Pharmacol Ther 2013; 94: 445-448.
- McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau J, Shi VC, Solomon SD, Swedberg K, Zile MR. Paradigm-HF Committees and Investigators. Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin-converting enzyme inhibition in patients with chronic systolic heart failure:rationale for and design of the prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in heart failure trial (PARADIGM-HF). Eur J Heart Fail 2013; 15: 1062-1073.
- Kubo T, Matsumura Y, Kitaoka H, Okawa M, Hirota T, Hamada T, Hitomi N, Hoshikawa E, Hayato K, Shimizu Y, Yamasaki N. Improvement in prognosis of dilated cardiomyopathy in the elderly over the past 20years. J Cardiol 2008; 52: 111-117.
- Du Q, Wu J, Wang H, Wang X, Xu L, Zhang Z, Liu J, Zhang J, Chen J, Hakonarson H, Hu A, Zhang L. Perindopril treatment promote left ventricle remodeling in patients with heart failure screened positive for autoantibodies against angiotensin II type 1 receptor. BMC Cardiovasc Disord 2013; 13: 94-101.
- Zhang L, Ding WY, Wang ZH, Tang MX, Wang F, Li Y, Zhong M, Zhang Y, Zhang W. Early administration of trimetazidine attenuates diabetic cardiomyopathy in rats by alleviating fibrosis, reducing apoptosis and enhancing autophagy. J Transl Med 2016; 14: 109.
- Shen LJ, Lu S, Zhou YH, Li L, Xing QM, Xu YL. Developing a rat model of dilated cardiomyopathy with improved survival. J Zhejiang Univ Sci 2016; B 17: 975-983.
- Hershberger RE, Morales A. Dilated cardiomyopathy overview. Genereviews[internet]. University of Washington, Seattle, 2018.
- Hao P, Yang J, Liu Y, Zhang M, Zhang K, Gao F, Chen Y, Zhang C, Zhang Y. Combination of angiotensin-(1–7) with perindopril is better than single therapy in ameliorating diabetic cardiomyopathy. Sci Rep 2015; 5: 8794.
- Tsioufis K, Andrikopoulos G, Manolis A. Trimetazidine and cardioprotection: facts and perspectives. Angiology 2015; 66: 204-210.
- Cattin ME, Ferry A, Vignaud A, Mougenot N, Jacquet A, Wahbi K, Bertrand AT, Bonne G. Mutation in lamin A/C sensitizes the myocardium to exercise-induced mechanical stress but has no effect on skeletal muscles in mouse. Neuromuscul Disord 2016; 26: 490-499.
- Nie Y, Luo F, Wang L, Yang T, Shi L, Li X, Shen J, Xu W, Guo T, Lin Q. Anti-hyperlipidemic effect of rice bran polysaccharide and its potential mechanism in high-fat diet mice. Food Func 2017; 8(11): 4028-4041.
- Lou Y, Yang J, Wang L, Chen X, Xin X, Liu Y. The clinical efficacy study of treatment to Chiari malformation type I with syringomyelia under the minimally invasive surgery of resection of Submeningeal cerebellar Tonsillar Herniation and reconstruction of Cisterna magna. Saudi J Biol Sci 2019; 26(8): 1927-1931.
- Lou Y, Guo D, Zhang H, Song L. Effectiveness of mesenchymal stems cells cultured by hanging drop vs. conventional culturing on the repair of hypoxic-ischemic-damaged mouse brains, measured by stemness gene expression. Open Life Sci 2016; 11(1): 519-523.
- Chen X, Xu Y, Meng L, Chen X, Yuan L, Cai Q, Shi W, Huang G. Non-parametric partial least squares–discriminant analysis model based on sum of ranking difference algorithm for tea grade identification using electronic tongue data identify tea grade using e-tongue data. Sens Actuators B Chem 2020; 127924.
- Nie Y, Luo F, Lin Q. Dietary nutrition and gut microflora: A promising target for treating diseases. Trends Food Sci Technol 2018;75: 72-80.
- Ren Y, Jiao X, Zhang L. Expression level of fibroblast growth factor 5 (FGF5) in the peripheral blood of primary hypertension and its clinical significance. Saudi J Biol Sci 2018; 25(3): 469-473.
- Raj P, Aloud BM, Louis XL, Yu L, Zieroth S, Netticadan T. Resveratrol is equipotent to perindopril in attenuating post-infarct cardiac remodeling and contractile dysfunction in rats. J Nutr Biochem 2016; 28: 155-163.
- McKie PM, Burnett JC. NT-proBNP: the gold standard biomarker in heart failure. J Am Coll Cardiol 2016; 68: 2437-2439.
- Sharma UC, Pokharel S, van Brakel TJ, van Berlo JH, Cleutjens JP, Schroen B, André S, Crijns HJ, Gabius HJ, Maessen J, Pinto YM. Galectin-3 marks activated macrophages in failure-prone hypertrophied hearts and contributes to cardiac dysfunction. Circulation 2004; 110: 3121-3128.
- Kawai T, Forrester SJ, O'Brien S, Baggett A, Rizzo V, Eguchi S. AT1 receptor signaling pathways in the cardiovascular system. Pharmacol Res 2017; 125: 4-13.
- Narula N, Favalli V, Tarantino P, Grasso M, Pilotto A, Bellazzi R, Serio A, Gambarin FI, Charron P, Meder B, Pinto Y. Quantitative expression of the mutated lamin A/C gene in patients with cardiolaminopathy. J Am Coll Cardiol 2012; 60: 1916-1920.
- Chatzifrangkeskou M, Le Dour C, Wu W, Morrow JP, Joseph LC, Beuvin M, Sera F, Homma S, Vignier N, Mougenot N, Bonne G. ERK1/2 directly acts on CTGF/CCN2 expression to mediate myocardial fibrosis in cardiomyopathy caused by mutations in the lamin A/C gene. Hum Mol Genet 2016; 25: 2220-2233.
- Nikolova V, Leimena C, McMahon AC, Tan JC, Chandar S, Jogia D, Kesteven SH, Michalicek J, Otway R, Verheyen F, Rainer S. Defects in nuclear structure and function promote dilated cardiomyopathy in lamin A/C–deficient mice. J Clin Invest 2004; 113: 357-369.
References
Weintraub RG, Semsarian C and Macdonald P: Dilated cardiomyopathy. Lancet 2017; 390: 400-414.
Merlo M, Cannatí A, Gobbo M, Stolfo D, Elliott PM, Sinagra G. Evolving concepts in dilated cardiomyopathy. Eur J Heart Fail 2018; 20: 228-239.
Hershberger RE, Hedges DJ and Morales A. The complexity of a diverse genetic architecture. Nat Rev Cardiol 2013; 10: 531-547.
Das S, Biswas A, Kapoor M, Seth S, Bhargava B, Rao VR. Epidemiology of cardiomyopathy–A clinical and genetic study of dilated cardiomyopathy: The EPOCH-D study. J Pract Cardiovasc Sci 2015; 1;1:30.
Lakdawala NK, Winterfield JR, Funke BH. Dilated cardiomyopathy. Circ Arrhythm Electrophysiol 2013; 6: 228-237.
Liang Y, Lin Q, Huang P, Wang Y, Li J, Zhang L and Cao J: Rice Bioactive Peptide Binding with TLR4 To Overcome H2O2-Induced Injury in Human Umbilical Vein Endothelial Cells through NF-κB Signaling. J Agri Food Chem 2018; 66(2): 440-448.
Wang L, Lin Q, Yang T, Liang Y, Nie Y, Luo Y and Luo F: Oryzanol modifies high fat diet-induced obesity, liver gene expression profile, and inflammation response in mice. J Agri Food Chem 2017; 65(38): 8374-8385.
Lou Y, Shi J, Guo D, Qureshi AK and Song L: Function of PD-L1 in antitumor immunity of glioma cells. Saudi J Boil Sci 2017; 24(4): 803-807.
Guo T, Lin Q, Li X, Nie Y, Wang L, Shi L and Luo F: Octacosanol attenuates inflammation in both RAW264. 7 macrophages and a mouse model of colitis. J Agri Food Chem 2017; 65(18): 3647-3658.
Li W, Jia MX, Wang JH, Lu JL, Deng J, Tang JX and Liu C: Association of MMP9-1562C/T and MMP13-77A/G polymorphisms with non-small cell lung cancer in southern Chinese population. Biomol 2019; 9(3): 107-119.
McNally EM, Golbus JR, Puckelwartz MJ. Genetic mutations and mechanisms in dilated cardiomyopathy. J Clin Invest 2013; 123: 19-26.
Bera M, Kumar R, Sinha B, Sengupta K. Nuclear deformation and anchorage defect induced by DCM mutants in lamin A. bioRxiv 2019; 1:611665.
Van Rijsingen IA, Arbustini E, Elliott PM, Mogensen J, Hermans-van Ast JF, Van Der Kooi AJ, Van Tintelen JP, Van Den Berg MP, Pilotto A, Pasotti M, Jenkins S. Risk factors for malignant ventricular arrhythmias in lamin A/C mutation carriers: a European cohort study. J Am Coll Cardiol 2012; 31;59(5):493-500.
Mathew T, Williams L, Navaratnam G, Rana B, Wheeler R, Collins K, Harkness A, Jones R, Knight D, O'Gallagher K, Oxborough D. Diagnosis and assessment of dilated cardiomyopathy:aguideline protocol from the British Society of Echocardiography. Echo Res Pract 2017; 4: G1-G13.
Madamanchi C, Alhosaini H, Sumida A and Runge MS. Obesity and natriuretic peptides, BNP and NT-proBNP: mechanisms and diagnostic implications for heart failure. Int J Cardiol 2014; 176: 611-617.
Koura HM, Abdalla NM, Hamed Ibrahim M, Abo Hashish MM and Zaki SM. NT-proBNP in children with left to right shunt and dilated cardiomyopathy. Iran J Pediatr 2016; 26: e4485.
von Lueder TG, Sangaralingham SJ, Wang BH, Kompa AR, Atar D, Burnett JC Jr, Krum H. Renin-angiotensin blockade combined with natriuretic peptide system augmentation: novel therapeutic concepts to combat heart failure. Circ Heart Fail 2013; 6: 594-605.
Vardeny O, Tacheny T, Solomon SD. First-in-class angiotensin receptor neprilysin inhibitor in heart failure. Clin Pharmacol Ther 2013; 94: 445-448.
McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau J, Shi VC, Solomon SD, Swedberg K, Zile MR. Paradigm-HF Committees and Investigators. Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin-converting enzyme inhibition in patients with chronic systolic heart failure:rationale for and design of the prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in heart failure trial (PARADIGM-HF). Eur J Heart Fail 2013; 15: 1062-1073.
Kubo T, Matsumura Y, Kitaoka H, Okawa M, Hirota T, Hamada T, Hitomi N, Hoshikawa E, Hayato K, Shimizu Y, Yamasaki N. Improvement in prognosis of dilated cardiomyopathy in the elderly over the past 20years. J Cardiol 2008; 52: 111-117.
Du Q, Wu J, Wang H, Wang X, Xu L, Zhang Z, Liu J, Zhang J, Chen J, Hakonarson H, Hu A, Zhang L. Perindopril treatment promote left ventricle remodeling in patients with heart failure screened positive for autoantibodies against angiotensin II type 1 receptor. BMC Cardiovasc Disord 2013; 13: 94-101.
Zhang L, Ding WY, Wang ZH, Tang MX, Wang F, Li Y, Zhong M, Zhang Y, Zhang W. Early administration of trimetazidine attenuates diabetic cardiomyopathy in rats by alleviating fibrosis, reducing apoptosis and enhancing autophagy. J Transl Med 2016; 14: 109.
Shen LJ, Lu S, Zhou YH, Li L, Xing QM, Xu YL. Developing a rat model of dilated cardiomyopathy with improved survival. J Zhejiang Univ Sci 2016; B 17: 975-983.
Hershberger RE, Morales A. Dilated cardiomyopathy overview. Genereviews[internet]. University of Washington, Seattle, 2018.
Hao P, Yang J, Liu Y, Zhang M, Zhang K, Gao F, Chen Y, Zhang C, Zhang Y. Combination of angiotensin-(1–7) with perindopril is better than single therapy in ameliorating diabetic cardiomyopathy. Sci Rep 2015; 5: 8794.
Tsioufis K, Andrikopoulos G, Manolis A. Trimetazidine and cardioprotection: facts and perspectives. Angiology 2015; 66: 204-210.
Cattin ME, Ferry A, Vignaud A, Mougenot N, Jacquet A, Wahbi K, Bertrand AT, Bonne G. Mutation in lamin A/C sensitizes the myocardium to exercise-induced mechanical stress but has no effect on skeletal muscles in mouse. Neuromuscul Disord 2016; 26: 490-499.
Nie Y, Luo F, Wang L, Yang T, Shi L, Li X, Shen J, Xu W, Guo T, Lin Q. Anti-hyperlipidemic effect of rice bran polysaccharide and its potential mechanism in high-fat diet mice. Food Func 2017; 8(11): 4028-4041.
Lou Y, Yang J, Wang L, Chen X, Xin X, Liu Y. The clinical efficacy study of treatment to Chiari malformation type I with syringomyelia under the minimally invasive surgery of resection of Submeningeal cerebellar Tonsillar Herniation and reconstruction of Cisterna magna. Saudi J Biol Sci 2019; 26(8): 1927-1931.
Lou Y, Guo D, Zhang H, Song L. Effectiveness of mesenchymal stems cells cultured by hanging drop vs. conventional culturing on the repair of hypoxic-ischemic-damaged mouse brains, measured by stemness gene expression. Open Life Sci 2016; 11(1): 519-523.
Chen X, Xu Y, Meng L, Chen X, Yuan L, Cai Q, Shi W, Huang G. Non-parametric partial least squares–discriminant analysis model based on sum of ranking difference algorithm for tea grade identification using electronic tongue data identify tea grade using e-tongue data. Sens Actuators B Chem 2020; 127924.
Nie Y, Luo F, Lin Q. Dietary nutrition and gut microflora: A promising target for treating diseases. Trends Food Sci Technol 2018;75: 72-80.
Ren Y, Jiao X, Zhang L. Expression level of fibroblast growth factor 5 (FGF5) in the peripheral blood of primary hypertension and its clinical significance. Saudi J Biol Sci 2018; 25(3): 469-473.
Raj P, Aloud BM, Louis XL, Yu L, Zieroth S, Netticadan T. Resveratrol is equipotent to perindopril in attenuating post-infarct cardiac remodeling and contractile dysfunction in rats. J Nutr Biochem 2016; 28: 155-163.
McKie PM, Burnett JC. NT-proBNP: the gold standard biomarker in heart failure. J Am Coll Cardiol 2016; 68: 2437-2439.
Sharma UC, Pokharel S, van Brakel TJ, van Berlo JH, Cleutjens JP, Schroen B, André S, Crijns HJ, Gabius HJ, Maessen J, Pinto YM. Galectin-3 marks activated macrophages in failure-prone hypertrophied hearts and contributes to cardiac dysfunction. Circulation 2004; 110: 3121-3128.
Kawai T, Forrester SJ, O'Brien S, Baggett A, Rizzo V, Eguchi S. AT1 receptor signaling pathways in the cardiovascular system. Pharmacol Res 2017; 125: 4-13.
Narula N, Favalli V, Tarantino P, Grasso M, Pilotto A, Bellazzi R, Serio A, Gambarin FI, Charron P, Meder B, Pinto Y. Quantitative expression of the mutated lamin A/C gene in patients with cardiolaminopathy. J Am Coll Cardiol 2012; 60: 1916-1920.
Chatzifrangkeskou M, Le Dour C, Wu W, Morrow JP, Joseph LC, Beuvin M, Sera F, Homma S, Vignier N, Mougenot N, Bonne G. ERK1/2 directly acts on CTGF/CCN2 expression to mediate myocardial fibrosis in cardiomyopathy caused by mutations in the lamin A/C gene. Hum Mol Genet 2016; 25: 2220-2233.
Nikolova V, Leimena C, McMahon AC, Tan JC, Chandar S, Jogia D, Kesteven SH, Michalicek J, Otway R, Verheyen F, Rainer S. Defects in nuclear structure and function promote dilated cardiomyopathy in lamin A/C–deficient mice. J Clin Invest 2004; 113: 357-369.