Cardioprotective potential of Rosuvastatin against isoproterenol induced cardiac dysfunction and hypertrophy in the experimental model of rodents

Abstract

Aims: Cardiovascular disease is the primary cause of mortality and morbidity, and its terminal phase is chronic heart failure. The present study aimed to examine the protective impact of rosuvastatin on isoproterenol-induced chronic heart failure and investigate plausible related mechanisms. Rosuvastatin, a drug with multiple pleiotropic properties, has been examined for its cardioprotective effects in heart failure induced by isoproterenol.

Methods: Male Sprague Dawley rats were given isoproterenol 5 mg/kg once a day for 7 days to establish heart failure by subcutaneous injection. Simultaneously, rosuvastatin (10 mg/kg) was orally administrated from day 1 to day 14. Protective effects were evaluated by heart grading and gross morphology, hemodynamic parameter, cardiac troponin I, heart mitochondrial enzyme and lysosomal hydrolases and pro inflammatory cytokines levels were analyzed.

Results: Rosuvastatin (10 mg/kg) significantly attenuated isoproterenol-induced hypertrophy, remodeling and dysfunction of the ventricle, reduced the heart mitochondrial enzyme and lysosomal hydrolases and normalized the increased hemodynamic and pro inflammatory cytokines levels.

Conclusions: The study highlights the preventive effects of, rosuvastatin, against heart failure. The results of the research indicate that rosuvastatin has cardioprotective effects on the experimental model, which were supported by several characteristics. However, further research is required to identify the precise molecular mechanisms and signalling pathways of rosuvastatin’s impact on heart failure.

Keywords

Heart failure / Left ventricular hypertrophy / Isoproterenol / Rosuvastatin

References

[1] Strandberg TE. Lipid-lowering drugs and heart failure: where do we go after the statin trials? Curr Opin Cardiol. 2010 Jul 1;25(4):385–393.

[2] Volpe M, Carnovali M, Mastromarino V. The natriuretic peptides system in the pathophysiology of heart failure: from molecular basis to treatment. Clin Sci. 2016 Jan 1;130(2):57–77.

[3] Glezeva N, Horgan S, Baugh JA. Monocyte and macrophage subsets along the continuum to heart failure: misguided heroes or targetable villains? J Mol Cell Cardiol. 2015 Dec 1;89:136–145.

[4] Münzel T, Gori T, Keaney Jr JF, Maack C, Daiber A. Pathophysiological role of oxidative stress in systolic and diastolic heart failure and its therapeutic implications. Eur Heart J. 2015 Oct 7;36(38):2555–2564.

[5] Shantsila E, Wrigley BJ, Blann AD, Gill PS, Lip GY. A contemporary view on endothelial function in heart failure. Eur J Heart Fail. 2012 Aug;14(8):873–881.

[6] Brower GL, Gardner JD, Forman MF, et al. The relationship between myocardial extracellular matrix remodeling and ventricular function. Eur J Cardio Thorac Surg. 2006 Oct 1;30(4):604–610.

[7] An L, An S, Jia Z, et al. Atorvastatin improves left ventricular remodeling and cardiac function in rats with congestive heart failure by inhibiting RhoA/Rho kinase-mediated endothelial nitric oxide synthase. Exp Ther Med. 2019 Jan 1;17(1):960–966.

[8] Freda BJ, Slawsky M, Mallidi J, Braden GL. Decongestive treatment of acute decompensated heart failure: cardiorenal implications of ultrafiltration and diuretics. Am J Kidney Dis. 2011 Dec 1;58(6):1005–1017.

[9] Yancy CW, Jessup M, Bozkurt B, et al. ACC/AHA/HFSA focused update on new pharmacological therapy for heart failure: an update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Am Coll Cardiol. 2016;68(13):1476–1488, 2016 Sep 27.

[10] Babelova A, Sedding DG, Brandes RP. Anti-atherosclerotic mechanisms of statin therapy. Curr Opin Pharmacol. 2013 Apr 1;13(2):260–264.

[11] Bauersachs J, Galuppo P, Fraccarollo D, Christ M, Ertl G. Improvement of left ventricular remodeling and function by hydroxymethylglutaryl coenzyme a reductase inhibition with cerivastatin in rats with heart failure after myocardial infarction. Circulation. 2001 Aug 28;104(9):982–985.

[12] Hayashidani S, Tsutsui H, Shiomi T, et al. Fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor, attenuates left ventricular remodeling and failure after experimental myocardial infarction. Circulation. 2002 Feb 19;105(7):868–873.

[13] Alehagen U, Benson L, Edner M, Dahlström U, Lund LH. Association between use of statins and mortality in patients with heart failure and ejection fraction of≥ 50. Circulation: Heart Fail. 2015 Sep;8(5):862–870.

[14] Wojnicz R, Wilczek K, Nowalany-Kozielska E, et al. Usefulness of atorvastatin in patients with heart failure due to inflammatory dilated cardiomyopathy and elevated cholesterol levels. Am J Cardiol. 2006 Mar 15;97(6):899–904.

[15] Sola S, Mir MQ, Khan BV, Lerakis S, Tandon N. Atorvastatin improves left ventricular systolic function and serum markers of inflammation in nonischemic heart failure. J Am Coll Cardiol. 2006 Jan 17;47(2):332–337.

[16] Horwich TB, MacLellan WR, Fonarow GC. Statin therapy is associated with improved survival in ischemic and non-ischemic heart failure. J Am Coll Cardiol. 2004 Feb 18;43(4):642–648.

[17] Laccarino G, Lefkowitz RJ, Koch WJ. Myocardial G protein-coupled receptor kinases: implications for heart failure therapy. Proc Assoc Am Phys. 1999 Sep;111(5):399–405.

[18] Ahsan F, Siddiqui HH, Mahmood T, Srivastav RK, Nayeem A. Evaluation of cardioprotective effect of Coleus forskohlii against isoprenaline induced myocardial infarction in rats. Indian J Pharmaceut Biol Res. 2014 Mar 20;2:17–25.

[19] Kaneko K, Susic D, Nunez E, Frohlich ED. Losartan reduces cardiac mass and improves coronary flow reserve in the spontaneously hypertensive rat. J Hypertens. 1996 May 1;14(5):645–653.

[20] Conchie J, Gelman AL, Levvy G. Inhibition of glycosidases by aldonolactones of corresponding configuration: the C-4-and C-6-specificity of β-glucosidase and β-galactosidase. Biochem J. 1967 Jun;103(3):609.

[21] Czarnecki CM, Salam A, Caldwell R, Jankus EF. Activity of alpha-1, 4-glucosidase in furazolidone-induced glycogenosis. Poultry Sci. 1978 Jan 1;57(1):301–303.

[22] Barrett TR, Ekstrand BR. Effect of sleep on memory: III. Controlling for time-of-day effects. J Exp Psychol. 1972 Dec;96(2):321.

[23] Sapolsky AL. Cathepsin-D activity in normal and ostearthritic human cartilage. InFed. Proc. 1973;32:1489–1493.

[24] Harrison DK, Fasching M, Fontana-Ayoub M, Gnaiger E. Cytochrome redox states and respiratory control in mouse and beef heart mitochondria at steady-state levels of hypoxia. J Appl Physiol. 2015 Nov 15;119(10):1210–1218.

[25] Bell JL, Baron DN. A colorimetric method for determination of isocitric dehydrogenase. Clin Chim Acta. 1960 Sep 1;5(5):740–747.

[26] Reed LJ, Mukherjee BB. [12] α-ketoglutarate dehydrogenase complex from Escherichia coli. InMethods in enzymology. 1969 Jan 1;13:55–61. Academic press.

[27] Slater EC, Bonner WD. The effect of fluoride on succinic oxidase system. Biochem J. 1952 Oct;52(2):185.

[28] Mehler AH, Kobnberg A, Gbisolia S, Ochoa S. The enzymatic mechanism of oxidation-redactions between malate or isocitrate and pyravate. J Biol Chem. 1948;174:961–977.

[29] Woodiwiss AJ, Tsotetsi OJ, Sprott S, et al. Reduction in myocardial collagen cross-linking parallels left ventricular dilatation in rat models of systolic chamber dysfunction. Circulation. 2001;103:155–160.

[30] Hong Y, Hui SC, Chan TY, Hou JY. Effect of berberine on regression of pressureoverload induced cardiac hypertrophy in rats. Am J Chin Med. 2002;30:589–599.

[31] Ni L, Zhou C, Duan Q, et al. β-AR blockers suppresses ER stress in cardiac hypertrophy and heart failure. PLoS One. 2011;6:e27294.

[32] Li J, Li P, Feng X, et al. Effects of losartan on pressure overload-induced cardiac gene expression profiling in rats. Clin Exp Pharmacol Physiol. 2003;30:827–832.

[33] Zhou MS, Jaimes EA, Raij L. Atorvastatin prevents end-organ injury in salt-sensitive hypertension: role of eNOS and oxidant stress. Hypertension. 2004;44:186–190.

[34] Ke D, Fang J, Fan L, Chen Z, Chen L. Regulatory T cells contribute to rosuvastatin-induced cardioprotection against ischemia-reperfusion injury. Coron Artery Dis. 2013 Jun 1;24(4):334–341.

[35] Du X, Hu X, Wei J. Postconditioning with rosuvastatin reduces myocardial ischemia-reperfusion injury by inhibiting high mobility group box 1 protein expression. Exp Ther Med. 2014;7(1):117–120.

[36] Anderson M, Moore D, Larson D. Comparison of isoproterenol and dobutamine in the induction of cardiac hypertrophy and fibrosis. Perfusion. 2008;23:231–235.

[37] Drews O, Tsukamoto O, Liem D, et al. Differential regulation of proteasome function in isoproterenol-induced cardiac hypertrophy. Circ Res. 2010;107:1094–1101.

[38] Patel V, Upaganlawar A, Zalawadia R, et al. Cardioprotective effect of melatonin against isoproterenol induced myocardial infarction in rats: a biochemical, electrocardiographic and histoarchitectural evaluation. Eur J Pharmacol. 2010;644:160–168.

[39] Judd JT, Wexler BC. Prolyl hydroxylase and collagen metabolism after experimental mycardial infarction. Am J Physiol Legacy Content. 1975 Jan 1;228(1):212–216.

[40] Henry JP, Stephens-Larson PA. Reduction of chronic psychosocial hypertension in mice by decaffeinated tea. Hypertension. 1984 May;6(3):437–444.

[41] Litwin SE, Katz SE, Weinberg EO, Lorell BH, Aurigemma GP, Douglas PS. Serial echocardiographic-Doppler assessment of left ventricular geometry and function in rats with pressure-overload hypertrophy: chronic angiotensin-converting enzyme inhibition attenuates the transition to heart failure. Circulation. 1995 May 15;91(10):2642–2654.

[42] Sorichter S, Mair J, Koller A, et al. Skeletal troponin I as a marker of exercise-induced muscle damage. J Appl Physiol. 1997 Oct 1;83(4):1076–1082.

[43] Bertinchant JP, Polge A, Mohty D, et al. Evaluation of incidence, clinical significance, and prognostic value of circulating cardiac troponin I and T elevation in hemodynamically stable patients with suspected myocardial contusion after blunt chest trauma. J Trauma Acute Care Surg. 2000 May 1;48(5):924–931.

[44] Chan YF, Marks ME, Jones FC, et al. Adaptive evolution of pelvic reduction in sticklebacks by recurrent deletion of a Pitx1 enhancer. Science. 2010 Jan 15;327(5963):302–305.

[45] York MR, Nagai T, Mangini AJ, Lemaire R, van Seventer JM, Lafyatis R. A macrophage marker, Siglec-1, is increased on circulating monocytes in patients with systemic sclerosis and induced by type I interferons and toll-like receptor agonists. Arthritis Rheum. 2007 Mar;56(3):1010–1020.

[46] Wallace LM, Beavan J, McCaffrey R, Darby D. Subduction zone coupling and tectonic block rotations in the North Island, New Zealand. J Geophys Res Solid Earth. 2004 Dec;109(B12).

[47] Lee JW, Devanarayan V, Barrett YC, et al. Fit-for-purpose method development and validation for successful biomarker measurement. Pharmaceut Res. 2006 Feb;23:312–328.

[48] Chen JW, Murphy TL, Willingham MC, Pastan I, August JT. Identification of two lysosomal membrane glycoproteins. J Cell Biol. 1985 Jul 1;101(1):85–95.

[49] Sathish V, Ebenezar KK, Devaki T. Synergistic effect of nicorandil and amlodipine on lysosomal hydrolases during experimental myocardial infarction in rats. Biomed Pharmacother. 2003 Sep 1;57(7):309–313.

[50] Ravichandran LV, Puvanakrishnan R. In vivo labeling studies on the biosynthesis and degradation of collagen in experimental myocardial infarction. Biochem Int. 1991 Jun 1;24(3):405–414.

[51] Akila P, Asaikumar L, Vennila L. Chlorogenic acid ameliorates isoproterenol-induced myocardial injury in rats by stabilizing mitochondrial and lysosomal enzymes. Biomed Pharmacother. 2017 Jan 1;85:582–591.

[52] Shah SB, Fridén J, Milner DJ, Capetenaki Y, Lieber RL. Structural and functional roles of desmin in mouse skeletal muscle during passive loading. In: Biophysical Society Annual Meeting, Boston, MA. 2002.

[53] Bloom S, Davis DL. Calcium as mediator of isoproterenol-induced myocardial necrosis. Am J Pathol. 1972 Dec;69(3):459.

[54] Chambers DE, Parks DA, Patterson G, et al. Xanthine oxidase as a source of free radical damage in myocardial ischemia. J Mol Cell Cardiol. 1985 Feb 1;17(2):145–152.

[55] Zhang XH, Maxwell SR, Thorpe GH, Thomason H, Rea CA, Connock MJ, Maslin DJ. The Action of Garlic upon Plasma Total Antioxidant Capacity.

[56] Ricciutti MA. Myocardial lysosome stability in the early stages of acute ischemic injury. Am J Cardiol. 1972 Oct 1;30(5):492–497.

[57] Ke D, Fang J, Fan L, Chen Z, Chen L. Regulatory T cells contribute to rosuvastatininduced cardioprotection against ischemia-reperfusion injury. Coron Artery Dis. 2013 Jun 1;24(4):334–341.

[58] Wang JQ, Wu GR, Wang Z, Dai XP, Li XR. Long-term clinical outcomes of statin use for chronic heart failure: a meta-analysis of 15 prospective studies. Heart Lung Circ. 2014 Feb 1;23(2):105–113.

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