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Published in: BMC Cardiovascular Disorders 1/2022

Open Access 01-12-2022 | Research

Metabolism disorder promotes isoproterenol-induced myocardial injury in mice with high temperature and high humidity and high-fat diet

Authors: Taohua Lan, Qiaohuang Zeng, Wei Jiang, Tong Liu, Wenjing Xu, Ping Yao, Weihui Lu

Published in: BMC Cardiovascular Disorders | Issue 1/2022

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Abstract

Background

Isoproterenol (ISO), a synthetic on selective β-adrenergic agonist, provides a simple and non-invasive method for inducing myocardial injury with lower mortality and higher reproducibility. Phlegm-damp syndrome, as known as “Tanshi” in Chinese, is one of Traditional Chinese Medicine (TCM) syndrome differentiation, which plays an important role in the development of cardiovascular diseases. However, the underlying mechanism remains unknown.

Methods

In our present study, a myocardial injury mouse model was introduced by ISO administration combined with high temperature and high humidity and high-fat diet to simulate phlegm-damp syndrome. Nontargeted metabolomics with LC–MS/MS was adopted to reveal serum metabolism profile for elucidating the possible molecular mechanism.

Results

The results of our study showed that phlegm-damp syndrome promoted ISO-induced myocardial injury by aggravating left ventricular hypertrophy and fibrosis, and increasing cardiac index. Our study also confirmed the presence of specific metabolites and disturbed metabolic pathways by comparing ISO mice and Tanshi mice, mainly including glycerophospholipid metabolism, arginine–proline metabolism, and sphingolipid signaling pathway. The lysoPCs, PCs, SMs, Sphingosine, and L-Arginine were the main metabolites that showed a difference between ISO and Tanshi mice, which might be the result of the underlying mechanism in the promotion of ISO-induced myocardial injury in mice with high temperature and high humidity and high-fat diet.

Conclusion

Our current study provides new insights into contribution of metabolism disorder in promotion of ISO-induced myocardial injury in mice with high temperature and high humidity and high-fat diet, and new targets for clinical diagnosis and pharmacologic treatment of cardiovascular disease with phlegm-damp syndrome.
Appendix
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Literature
1.
go back to reference Garg M, Khanna D. Exploration of pharmacological interventions to prevent isoproterenol-induced myocardial infarction in experimental models. Ther Adv Cardiovasc Dis. 2014;8:155–69.CrossRef Garg M, Khanna D. Exploration of pharmacological interventions to prevent isoproterenol-induced myocardial infarction in experimental models. Ther Adv Cardiovasc Dis. 2014;8:155–69.CrossRef
2.
go back to reference Wong ZW, Thanikachalam PV, Ramamurthy S. Molecular understanding of the protective role of natural products on isoproterenol-induced myocardial infarction: a review. Biomed Pharmacother. 2017;94:1145–66.CrossRef Wong ZW, Thanikachalam PV, Ramamurthy S. Molecular understanding of the protective role of natural products on isoproterenol-induced myocardial infarction: a review. Biomed Pharmacother. 2017;94:1145–66.CrossRef
3.
go back to reference Ou CQ, Yang J, Ou QQ, Liu HZ, Lin GZ, Chen PY, et al. The impact of relative humidity and atmospheric pressure on mortality in Guangzhou, China. Biomed Environ Sci. 2014;27:917–25.PubMed Ou CQ, Yang J, Ou QQ, Liu HZ, Lin GZ, Chen PY, et al. The impact of relative humidity and atmospheric pressure on mortality in Guangzhou, China. Biomed Environ Sci. 2014;27:917–25.PubMed
4.
go back to reference Ding N, Berry HL, Bennett CM. The importance of humidity in the relationship between heat and population mental health: evidence from Australia. PLoS ONE. 2016;11:e164190. Ding N, Berry HL, Bennett CM. The importance of humidity in the relationship between heat and population mental health: evidence from Australia. PLoS ONE. 2016;11:e164190.
5.
go back to reference Gasparrini A, Guo Y, Hashizume M, Lavigne E, Zanobetti A, Schwartz J, et al. Mortality risk attributable to high and low ambient temperature: a multicountry observational study. Lancet. 2015;386:369–75.CrossRef Gasparrini A, Guo Y, Hashizume M, Lavigne E, Zanobetti A, Schwartz J, et al. Mortality risk attributable to high and low ambient temperature: a multicountry observational study. Lancet. 2015;386:369–75.CrossRef
6.
go back to reference Ruiz-Canela M, Hruby A, Clish CB, Liang L, Martinez-Gonzalez MA, Hu FB. Comprehensive metabolomic profiling and incident cardiovascular disease: a systematic review. J Am Heart Assoc. 2017;6:e005705.CrossRef Ruiz-Canela M, Hruby A, Clish CB, Liang L, Martinez-Gonzalez MA, Hu FB. Comprehensive metabolomic profiling and incident cardiovascular disease: a systematic review. J Am Heart Assoc. 2017;6:e005705.CrossRef
7.
go back to reference Zhang J, Chen Z, Lu Y, Tu D, Zou F, Lin S, et al. A functional food inhibits azoxymethane/dextran sulfate sodium-induced inflammatory colorectal cancer in mice. OncoTargets Ther. 2021;14:1465–77.CrossRef Zhang J, Chen Z, Lu Y, Tu D, Zou F, Lin S, et al. A functional food inhibits azoxymethane/dextran sulfate sodium-induced inflammatory colorectal cancer in mice. OncoTargets Ther. 2021;14:1465–77.CrossRef
8.
go back to reference Xuan Q, Ouyang Y, Wang Y, Wu L, Li H, Luo Y, et al. Multiplatform metabolomics reveals novel serum metabolite biomarkers in diabetic retinopathy subjects. Adv Sci (Weinh). 2020;7:2001714.CrossRef Xuan Q, Ouyang Y, Wang Y, Wu L, Li H, Luo Y, et al. Multiplatform metabolomics reveals novel serum metabolite biomarkers in diabetic retinopathy subjects. Adv Sci (Weinh). 2020;7:2001714.CrossRef
9.
go back to reference Isogai N, Shiono Y, Kuramoto T, Yoshioka K, Ishihama H, Funao H, et al. Potential osteomyelitis biomarkers identified by plasma metabolome analysis in mice. Sci Rep. 2020;10:839.CrossRef Isogai N, Shiono Y, Kuramoto T, Yoshioka K, Ishihama H, Funao H, et al. Potential osteomyelitis biomarkers identified by plasma metabolome analysis in mice. Sci Rep. 2020;10:839.CrossRef
10.
go back to reference Nichtova Z, Novotova M, Kralova E, Stankovicova T. Morphological and functional characteristics of models of experimental myocardial injury induced by isoproterenol. Gen Physiol Biophys. 2012;31:141–51.CrossRef Nichtova Z, Novotova M, Kralova E, Stankovicova T. Morphological and functional characteristics of models of experimental myocardial injury induced by isoproterenol. Gen Physiol Biophys. 2012;31:141–51.CrossRef
11.
go back to reference Doenst T, Nguyen TD, Abel ED. Cardiac metabolism in heart failure: implications beyond ATP production. Circ Res. 2013;113:709–24.CrossRef Doenst T, Nguyen TD, Abel ED. Cardiac metabolism in heart failure: implications beyond ATP production. Circ Res. 2013;113:709–24.CrossRef
12.
go back to reference Dang VT, Huang A, Werstuck GH. Untargeted metabolomics in the discovery of novel biomarkers and therapeutic targets for atherosclerotic cardiovascular diseases. Cardiovasc Hematol Disord Drug Targets. 2018;18:166–75.CrossRef Dang VT, Huang A, Werstuck GH. Untargeted metabolomics in the discovery of novel biomarkers and therapeutic targets for atherosclerotic cardiovascular diseases. Cardiovasc Hematol Disord Drug Targets. 2018;18:166–75.CrossRef
13.
go back to reference Fan Y, Li Y, Chen Y, Zhao YJ, Liu LW, Li J, et al. Comprehensive metabolomic characterization of coronary artery diseases. J Am Coll Cardiol. 2016;68:1281–93.CrossRef Fan Y, Li Y, Chen Y, Zhao YJ, Liu LW, Li J, et al. Comprehensive metabolomic characterization of coronary artery diseases. J Am Coll Cardiol. 2016;68:1281–93.CrossRef
14.
go back to reference Ussher JR, Elmariah S, Gerszten RE, Dyck JR. The emerging role of metabolomics in the diagnosis and prognosis of cardiovascular disease. J Am Coll Cardiol. 2016;68:2850–70.CrossRef Ussher JR, Elmariah S, Gerszten RE, Dyck JR. The emerging role of metabolomics in the diagnosis and prognosis of cardiovascular disease. J Am Coll Cardiol. 2016;68:2850–70.CrossRef
15.
go back to reference McGarrah RW, Crown SB, Zhang GF, Shah SH, Newgard CB. Cardiovascular metabolomics. Circ Res. 2018;122:1238–58.CrossRef McGarrah RW, Crown SB, Zhang GF, Shah SH, Newgard CB. Cardiovascular metabolomics. Circ Res. 2018;122:1238–58.CrossRef
17.
go back to reference Lai L, Leone TC, Keller MP, Martin OJ, Broman AT, Nigro J, et al. Energy metabolic reprogramming in the hypertrophied and early stage failing heart: a multisystems approach. Circ Heart Fail. 2014;7:1022–31.CrossRef Lai L, Leone TC, Keller MP, Martin OJ, Broman AT, Nigro J, et al. Energy metabolic reprogramming in the hypertrophied and early stage failing heart: a multisystems approach. Circ Heart Fail. 2014;7:1022–31.CrossRef
18.
go back to reference Sun H, Olson KC, Gao C, Prosdocimo DA, Zhou M, Wang Z, et al. Catabolic defect of branched-chain amino acids promotes heart failure. Circulation. 2016;133:2038–49.CrossRef Sun H, Olson KC, Gao C, Prosdocimo DA, Zhou M, Wang Z, et al. Catabolic defect of branched-chain amino acids promotes heart failure. Circulation. 2016;133:2038–49.CrossRef
19.
go back to reference Wang W, Zhang F, Xia Y, Zhao S, Yan W, Wang H, et al. Defective branched chain amino acid catabolism contributes to cardiac dysfunction and remodeling following myocardial infarction. Am J Physiol Heart Circ Physiol. 2016;311:H1160–9.CrossRef Wang W, Zhang F, Xia Y, Zhao S, Yan W, Wang H, et al. Defective branched chain amino acid catabolism contributes to cardiac dysfunction and remodeling following myocardial infarction. Am J Physiol Heart Circ Physiol. 2016;311:H1160–9.CrossRef
20.
go back to reference Aubert G, Martin OJ, Horton JL, Lai L, Vega RB, Leone TC, et al. The failing heart relies on ketone bodies as a fuel. Circulation. 2016;133:698–705.CrossRef Aubert G, Martin OJ, Horton JL, Lai L, Vega RB, Leone TC, et al. The failing heart relies on ketone bodies as a fuel. Circulation. 2016;133:698–705.CrossRef
21.
go back to reference Bedi KJ, Snyder NW, Brandimarto J, Aziz M, Mesaros C, Worth AJ, et al. Evidence for intramyocardial disruption of lipid metabolism and increased myocardial ketone utilization in advanced human heart failure. Circulation. 2016;133:706–16.CrossRef Bedi KJ, Snyder NW, Brandimarto J, Aziz M, Mesaros C, Worth AJ, et al. Evidence for intramyocardial disruption of lipid metabolism and increased myocardial ketone utilization in advanced human heart failure. Circulation. 2016;133:706–16.CrossRef
22.
go back to reference Shah SH, Bain JR, Muehlbauer MJ, Stevens RD, Crosslin DR, Haynes C, et al. Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events. Circ Cardiovasc Genet. 2010;3:207–14.CrossRef Shah SH, Bain JR, Muehlbauer MJ, Stevens RD, Crosslin DR, Haynes C, et al. Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events. Circ Cardiovasc Genet. 2010;3:207–14.CrossRef
23.
go back to reference Bhattacharya S, Granger CB, Craig D, Haynes C, Bain J, Stevens RD, et al. Validation of the association between a branched chain amino acid metabolite profile and extremes of coronary artery disease in patients referred for cardiac catheterization. Atherosclerosis. 2014;232:191–6.CrossRef Bhattacharya S, Granger CB, Craig D, Haynes C, Bain J, Stevens RD, et al. Validation of the association between a branched chain amino acid metabolite profile and extremes of coronary artery disease in patients referred for cardiac catheterization. Atherosclerosis. 2014;232:191–6.CrossRef
24.
go back to reference Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011;472:57–63.CrossRef Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011;472:57–63.CrossRef
25.
go back to reference Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013;368:1575–84.CrossRef Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013;368:1575–84.CrossRef
26.
go back to reference Shah SH, Sun JL, Stevens RD, Bain JR, Muehlbauer MJ, Pieper KS, et al. Baseline metabolomic profiles predict cardiovascular events in patients at risk for coronary artery disease. Am Heart J. 2012;163:844–50.CrossRef Shah SH, Sun JL, Stevens RD, Bain JR, Muehlbauer MJ, Pieper KS, et al. Baseline metabolomic profiles predict cardiovascular events in patients at risk for coronary artery disease. Am Heart J. 2012;163:844–50.CrossRef
27.
go back to reference Zhang HY, Chen X, Hu P, Liang QL, Liang XP, Wang YM, et al. Metabolomic profiling of rat serum associated with isoproterenol-induced myocardial infarction using ultra-performance liquid chromatography/time-of-flight mass spectrometry and multivariate analysis. Talanta. 2009;79:254–9.CrossRef Zhang HY, Chen X, Hu P, Liang QL, Liang XP, Wang YM, et al. Metabolomic profiling of rat serum associated with isoproterenol-induced myocardial infarction using ultra-performance liquid chromatography/time-of-flight mass spectrometry and multivariate analysis. Talanta. 2009;79:254–9.CrossRef
28.
go back to reference Liu YT, Jia HM, Chang X, Ding G, Zhang HW, Zou ZM. The metabolic disturbances of isoproterenol induced myocardial infarction in rats based on a tissue targeted metabonomics. Mol Biosyst. 2013;9:2823–34.CrossRef Liu YT, Jia HM, Chang X, Ding G, Zhang HW, Zou ZM. The metabolic disturbances of isoproterenol induced myocardial infarction in rats based on a tissue targeted metabonomics. Mol Biosyst. 2013;9:2823–34.CrossRef
29.
go back to reference Goulart V, Santos AK, Sandrim VC, Batista JM, Pinto M, Cameron LC, et al. Metabolic disturbances identified in plasma samples from ST-segment elevation myocardial infarction patients. Dis Markers. 2019;2019:7676189.CrossRef Goulart V, Santos AK, Sandrim VC, Batista JM, Pinto M, Cameron LC, et al. Metabolic disturbances identified in plasma samples from ST-segment elevation myocardial infarction patients. Dis Markers. 2019;2019:7676189.CrossRef
30.
go back to reference Park JY, Lee SH, Shin MJ, Hwang GS. Alteration in metabolic signature and lipid metabolism in patients with angina pectoris and myocardial infarction. PLoS ONE. 2015;10:e135228. Park JY, Lee SH, Shin MJ, Hwang GS. Alteration in metabolic signature and lipid metabolism in patients with angina pectoris and myocardial infarction. PLoS ONE. 2015;10:e135228.
31.
go back to reference Zheng X, Li W, Ren L, Liu J, Pang X, Chen X, et al. The sphingosine kinase-1/sphingosine-1-phosphate axis in cancer: Potential target for anticancer therapy. Pharmacol Ther. 2019;195:85–99.CrossRef Zheng X, Li W, Ren L, Liu J, Pang X, Chen X, et al. The sphingosine kinase-1/sphingosine-1-phosphate axis in cancer: Potential target for anticancer therapy. Pharmacol Ther. 2019;195:85–99.CrossRef
32.
go back to reference Van Brocklyn JR, Williams JB. The control of the balance between ceramide and sphingosine-1-phosphate by sphingosine kinase: oxidative stress and the seesaw of cell survival and death. Comp Biochem Physiol B Biochem Mol Biol. 2012;163:26–36.CrossRef Van Brocklyn JR, Williams JB. The control of the balance between ceramide and sphingosine-1-phosphate by sphingosine kinase: oxidative stress and the seesaw of cell survival and death. Comp Biochem Physiol B Biochem Mol Biol. 2012;163:26–36.CrossRef
33.
go back to reference Hait NC, Oskeritzian CA, Paugh SW, Milstien S, Spiegel S. Sphingosine kinases, sphingosine 1-phosphate, apoptosis and diseases. Biochim Biophys Acta. 2006;1758:2016–26.CrossRef Hait NC, Oskeritzian CA, Paugh SW, Milstien S, Spiegel S. Sphingosine kinases, sphingosine 1-phosphate, apoptosis and diseases. Biochim Biophys Acta. 2006;1758:2016–26.CrossRef
34.
go back to reference Thielmann M, Dorge H, Martin C, Belosjorow S, Schwanke U, van De Sand A, et al. Myocardial dysfunction with coronary microembolization: signal transduction through a sequence of nitric oxide, tumor necrosis factor-alpha, and sphingosine. Circ Res. 2002;90:807–13.CrossRef Thielmann M, Dorge H, Martin C, Belosjorow S, Schwanke U, van De Sand A, et al. Myocardial dysfunction with coronary microembolization: signal transduction through a sequence of nitric oxide, tumor necrosis factor-alpha, and sphingosine. Circ Res. 2002;90:807–13.CrossRef
35.
go back to reference Tousoulis D, Antoniades C, Tentolouris C, Goumas G, Stefanadis C, Toutouzas P. L-arginine in cardiovascular disease: dream or reality? Vasc Med. 2002;7:203–11.CrossRef Tousoulis D, Antoniades C, Tentolouris C, Goumas G, Stefanadis C, Toutouzas P. L-arginine in cardiovascular disease: dream or reality? Vasc Med. 2002;7:203–11.CrossRef
36.
go back to reference Ren J, Yang L, Tian W, Zhu M, Liu J, Lu P, et al. Nitric oxide synthase inhibition abolishes exercise-mediated protection against isoproterenol-induced cardiac hypertrophy in female mice. Cardiology. 2015;130:175–84.CrossRef Ren J, Yang L, Tian W, Zhu M, Liu J, Lu P, et al. Nitric oxide synthase inhibition abolishes exercise-mediated protection against isoproterenol-induced cardiac hypertrophy in female mice. Cardiology. 2015;130:175–84.CrossRef
37.
go back to reference Lin Y, Wang LN, Xi YH, Li HZ, Xiao FG, Zhao YJ, et al. L-arginine inhibits isoproterenol-induced cardiac hypertrophy through nitric oxide and polyamine pathways. Basic Clin Pharmacol Toxicol. 2008;103:124–30.CrossRef Lin Y, Wang LN, Xi YH, Li HZ, Xiao FG, Zhao YJ, et al. L-arginine inhibits isoproterenol-induced cardiac hypertrophy through nitric oxide and polyamine pathways. Basic Clin Pharmacol Toxicol. 2008;103:124–30.CrossRef
Metadata
Title
Metabolism disorder promotes isoproterenol-induced myocardial injury in mice with high temperature and high humidity and high-fat diet
Authors
Taohua Lan
Qiaohuang Zeng
Wei Jiang
Tong Liu
Wenjing Xu
Ping Yao
Weihui Lu
Publication date
01-12-2022
Publisher
BioMed Central
Published in
BMC Cardiovascular Disorders / Issue 1/2022
Electronic ISSN: 1471-2261
DOI
https://doi.org/10.1186/s12872-022-02583-z

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