Integrated mass spectrometry imaging reveals spatial-metabolic alteration in diabetic cardiomyopathy and the intervention effects of ferulic acid

Yanhua Liu; Xin Zhang; Shu Yang; Zhi Zhou; Lu Tian; Wanfang Li; Jinfeng Wei; Zeper Abliz; Zhonghua Wang

doi:10.1016/j.jpha.2023.08.011

Volume 13 Issue 12

Dec. 2023

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Yanhua Liu, Xin Zhang, Shu Yang, Zhi Zhou, Lu Tian, Wanfang Li, Jinfeng Wei, Zeper Abliz, Zhonghua Wang. Integrated mass spectrometry imaging reveals spatial-metabolic alteration in diabetic cardiomyopathy and the intervention effects of ferulic acid[J]. Journal of Pharmaceutical Analysis, 2023, 13(12): 1496-1509. doi: 10.1016/j.jpha.2023.08.011

Citation:

Yanhua Liu, Xin Zhang, Shu Yang, Zhi Zhou, Lu Tian, Wanfang Li, Jinfeng Wei, Zeper Abliz, Zhonghua Wang. Integrated mass spectrometry imaging reveals spatial-metabolic alteration in diabetic cardiomyopathy and the intervention effects of ferulic acid[J]. Journal of Pharmaceutical Analysis, 2023, 13(12): 1496-1509. doi: 10.1016/j.jpha.2023.08.011

Citation:

Yanhua Liu, Xin Zhang, Shu Yang, Zhi Zhou, Lu Tian, Wanfang Li, Jinfeng Wei, Zeper Abliz, Zhonghua Wang. Integrated mass spectrometry imaging reveals spatial-metabolic alteration in diabetic cardiomyopathy and the intervention effects of ferulic acid[J]. Journal of Pharmaceutical Analysis, 2023, 13(12): 1496-1509. doi: 10.1016/j.jpha.2023.08.011

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Integrated mass spectrometry imaging reveals spatial-metabolic alteration in diabetic cardiomyopathy and the intervention effects of ferulic acid

doi: 10.1016/j.jpha.2023.08.011

Yanhua Liu^a,b,
Xin Zhang^a,b,
Shu Yang^a,b,
Zhi Zhou^a,b,
Lu Tian^c,
Wanfang Li^c,
Jinfeng Wei^c,
Zeper Abliz^{a,b,d
,
,},
Zhonghua Wang^{a,b,d
,
,}

a. Key Laboratory of Mass Spectrometry Imaging and Metabolomics (Minzu University of China), National Ethnic Affairs Commission, Beijing, 100081, China;
b. Center for Imaging and Systems Biology, College of Life and Environmental Sciences, Minzu University of China, Beijing, 100081, China;
c. New Drug Safety Evaluation Center, Institute of Materia Medica, Peking Union Medical College, Beijing, 100050, China;
d. Key Laboratory of Ethnomedicine of Ministry of Education, School of Pharmacy, Minzu University of China, Beijing, 100081, China

Funds:

This work was supported by the National Natural Science Foundation of China (Grant Nos.: 21927808 and 81803483).

Received Date: May 30, 2023
Accepted Date: Aug. 10, 2023
Rev Recd Date: Jul. 28, 2023
Publish Date: Aug. 17, 2023

Abstract

Abstract

Diabetic cardiomyopathy (DCM) is a metabolic disease and a leading cause of heart failure among people with diabetes. Mass spectrometry imaging (MSI) is a versatile technique capable of combining the molecular specificity of mass spectrometry (MS) with the spatial information of imaging. In this study, we used MSI to visualize metabolites in the rat heart with high spatial resolution and sensitivity. We optimized the air flow-assisted desorption electrospray ionization (AFADESI)-MSI platform to detect a wide range of metabolites, and then used matrix-assisted laser desorption ionization (MALDI)-MSI for increasing metabolic coverage and improving localization resolution. AFADESI-MSI detected 214 and 149 metabolites in positive and negative analyses of rat heart sections, respectively, while MALDI-MSI detected 61 metabolites in negative analysis. Our study revealed the heterogenous metabolic profile of the heart in a DCM model, with over 105 region-specific changes in the levels of a wide range of metabolite classes, including carbohydrates, amino acids, nucleotides, and their derivatives, fatty acids, glycerol phospholipids, carnitines, and metal ions. The repeated oral administration of ferulic acid during 20 weeks significantly improved most of the metabolic disorders in the DCM model. Our findings provide novel insights into the molecular mechanisms underlying DCM and the potential of ferulic acid as a therapeutic agent for treating this condition.
- Mass spectrometry imaging,
- Diabetic cardiomyopathy,
- Metabolic reprogramming,
- Ferulic acid

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References(69)

References

[1]	J. Bene, K. Hadzsiev, B. Melegh, Role of carnitine and its derivatives in the development and management of type 2 diabetes, Nutr. Diabetes 8 (2018), 8.
[2]	G.E. Gilca, G. Stefanescu, O. Badulescu, et al., Diabetic cardiomyopathy: current approach and potential diagnostic and therapeutic targets, J. Diabetes Res. 2017 (2017) 1-7.
[3]	M. Nakamura, J. Sadoshima, Cardiomyopathy in obesity, insulin resistance and diabetes, J. Physiol. 598 (2020) 2977-2993.
[4]	M. Tate, D. Prakoso, A.M. Willis, et al., Characterising an alternative murine model of diabetic cardiomyopathy, Front. Physiol. 10 (2019), 1395.
[5]	H.Tsutsui, S. Kinugawa, S. Matsushima, Oxidative stress and heart failure, Am. J. Physiol. Heart Circ. Physiol. 301 (2011) H2181-H2190.
[6]	W. Li, M. Yao, R. Wang, et al., Profile of cardiac lipid metabolism in STZ-induced diabetic mice, Lipids Health Dis. 17 (2018), 231.
[7]	E. Anderson, J.L. Durstine, Physical activity, exercise, and chronic diseases: a brief review, Sports. Med. Health. Sci. 1 (2019) 3-10.
[8]	G.D. Lopaschuk, Q.G. Karwi, R. Tian, et al., Cardiac energy metabolism in heart failure, Circ. Res. 128 (2021) 1487-1513.
[9]	C.B. Lietz, E. Gemperline, L. Li, Qualitative and quantitative mass spectrometry imaging of drugs and metabolites, Adv. Drug Deliv. Rev. 65 (2013) 1074-1085.
[10]	H. Jiang, Y. Zhang, Z. Liu, et al., Advanced applications of mass spectrometry imaging technology in quality control and safety assessments of traditional Chinese medicines, J. Ethnopharmacol. 284 (2022), 114760.
[11]	J.L. Norris, R.M. Caprioli, Analysis of tissue specimens by matrix-assisted laser desorption/ionization imaging mass spectrometry in biological and clinical research, Chem. Rev. 113 (2013) 2309-2342.
[12]	R.M. Caprioli, T.B. Farmer, J. Gile, Molecular imaging of biological samples: localization of peptides and proteins using MALDI-TOF MS, Anal. Chem. 69 (1997) 4751-4760.
[13]	K.Y. Garza, C.L. Feider, D.R. Klein, et al., Desorption electrospray ionization mass spectrometry imaging of proteins directly from biological tissue sections, Anal. Chem. 90 (2018) 7785-7789.
[14]	Y. Li, B. Shrestha, A. Vertes, Atmospheric pressure molecular imaging by infrared MALDI mass spectrometry, Anal. Chem. 79 (2007) 523-532.
[15]	A. Nordstrom, E. Want, T. Northen, et al., Multiple ionization mass spectrometry strategy used to reveal the complexity of metabolomics, Anal. Chem. 80 (2008) 421-429.
[16]	R. Shroff, L. Rulisek, J. Doubsky, et al., Acid-base-driven matrix-assisted mass spectrometry for targeted metabolomics, Proc. Natl. Acad. Sci. U S A 106 (2009) 10092-10096.
[17]	T. Muller, S. Oradu, D.R. Ifa, et al., Direct plant tissue analysis and imprint imaging by desorption electrospray ionization mass spectrometry, Anal. Chem. 83 (2011) 5754-5761.
[18]	K.A. Douglass, A.R. Venter, Protein analysis by desorption electrospray ionization mass spectrometry and related methods, J. Mass Spectrom. 48 (2013) 553-560.
[19]	Y. Zhu, Q. Zang, Z. Luo, et al., An organ-specific metabolite annotation approach for ambient mass spectrometry imaging reveals spatial metabolic alterations of a whole mouse body, Anal. Chem. 94 (2022) 7286-7294.
[20]	V.L. Brown, L. He, Current status and future prospects of mass spectrometry imaging of small molecules. Mass Spectrometry Imaging of Small Molecules, Vol. 1203, Humana Press, New York, 2015, pp 1–7.
[21]	R.F. Menger, W.L. Stutts, D.S. Anbukumar, et al., MALDI mass spectrometric imaging of cardiac tissue following myocardial infarction in a rat coronary artery ligation model, Anal. Chem. 84 (2012) 1117-1125.
[22]	K. Margulis, Z. Zhou, Q. Fang, et al., Combining desorption electrospray ionization mass spectrometry imaging and machine learning for molecular recognition of myocardial infarction, Anal. Chem. 90 (2018) 12198-12206.
[23]	X. Li, J. Wu, F. Xu, et al., Use of ferulic acid in the management of diabetes mellitus and its complications, Molecules 27 (2022), 6010.
[24]	S. Anjali, N.P. Padmakumari Soumya, S. Mondal, et al., Cardioprotective effects of ferulic acid in streptozotocin-induced diabetic rats, Bioact. Compd. Heath. Dis. 5 (2022), 149.
[25]	L. Ye, P. Hu, L. Feng, et al., Protective effects of ferulic acid on metabolic syndrome: a comprehensive review, Molecules 28 (2022), 281.
[26]	H. Liu, R. Chen, J. Wang, et al., 1,5-Diaminonaphthalene hydrochloride assisted laser desorption/ionization mass spectrometry imaging of small molecules in tissues following focal cerebral ischemia, Anal. Chem. 86 (2014) 10114-10121.
[27]	M. Huo, Z. Wang, W. Fu, et al., Spatially resolved metabolomics based on air-flow-assisted desorption electrospray ionization-mass spectrometry imaging reveals region-specific metabolic alterations in diabetic encephalopathy, J. Proteome Res. 20 (2021) 3567-3579.
[28]	Z. Wang, W. Fu, M. Huo, et al., Spatial-resolved metabolomics reveals tissue-specific metabolic reprogramming in diabetic nephropathy by using mass spectrometry imaging, Acta Pharm. Sin. B 11 (2021) 3665-3677.
[29]	D.S. Wishart, Y.D. Feunang, A. Marcu, et al., HMDB 4.0: the human metabolome database for 2018, Nucleic Acids Res. 46 (2018) D608-D617.
[30]	C.A. Smith, G. O'Maille, E.J. Want, et al., METLIN: a metabolite mass spectral database, Ther. Drug Monit. 27 (2005) 747-751.
[31]	M. Sud, E. Fahy, D. Cotter, et al., LMSD: LIPID MAPS structure database, Nucleic Acids Res. 35 (2007) D527-D532.
[32]	P.A. Gorski, D.K. Ceholski, R.J. Hajjar, Altered myocardial calcium cycling and energetics in heart failure: a rational approach for disease treatment, Cell Metab. 21 (2015) 183-194.
[33]	D.J. Hamilton, Mechanisms of disease: is mitochondrial function altered in heart failure? Methodist DeBakey Cardiovasc. J. 9 (2013) 44-48.
[34]	S. Alvarez, T. Vico, V. Vanasco, Cardiac dysfunction, mitochondrial architecture, energy production, and inflammatory pathways: Interrelated aspects in endotoxemia and sepsis, Int. J. Biochem. Cell Biol. 81 (2016) 307-314.
[35]	L.J. De Meirleir, M. Brivet, A. Garcia-Cazorla, Disorders of pyruvate metabolism and the tricarboxylic acid cycle. Inborn Metabolic Diseases, Springer, Berlin, 2012, pp. 187–200.
[36]	P. Rustin, A. Munnich, A. Rotig, Succinate dehydrogenase and human diseases: new insights into a well-known enzyme, Eur. J. Hum. Genet. 10 (2002) 289-291.
[37]	K. YuYe, T.O. Yastreb, V. Karpets Yu, et al., Influence of salicylic and succinic acids on antioxidant enzymes activity, heat resistance and productivity of Panicum miliaceum L., J. Stress Physiol. Biochem. 7 (2011) 154-163.
[38]	H.C. Yoo, Y. Yu, Y. Sung, et al., Glutamine reliance in cell metabolism, Exp. Mol. Med. 52 (2020) 1496-1516.
[39]	G. Marazzi, S. Rosanio, G. Caminiti, et al., The role of amino acids in the modulation of cardiac metabolism during ischemia and heart failure, Curr. Pharm. Des. 14 (2008) 2592-2604.
[40]	F. Triposkiadis, G. Karayannis, G. Giamouzis, et al., The sympathetic nervous system in heart failure physiology, pathophysiology, and clinical implications, J. Am. Coll. Cardiol. 54 (2009) 1747-1762.
[41]	H. Nakamura, S. Matoba, E. Iwai-Kanai, et al., p53 promotes cardiac dysfunction in diabetic mellitus caused by excessive mitochondrial respiration-mediated reactive oxygen species generation and lipid accumulation, Circ. Heart Fail. 5 (2012) 106-115.
[42]	L.Salvado, T. Coll, A.M. Gomez-Foix, et al., Oleate prevents saturated-fatty-acid-induced ER stress, inflammation and insulin resistance in skeletal muscle cells through an AMPK-dependent mechanism, Diabetologia 56 (2013) 1372-1382.
[43]	Y. Wei, D. Wang, F. Topczewski, et al., Saturated fatty acids induce endoplasmic reticulum stress and apoptosis independently of ceramide in liver cells, Am. J. Physiol. Endocrinol. Metab. 291 (2006) E275-E281.
[44]	R.S. Khan, A. Chokshi, K. Drosatos, et al., Fish oil selectively improves heart function in a mouse model of lipid-induced cardiomyopathy, J. Cardiovasc. Pharmacol. 61 (2013) 345-354.
[45]	L.M. Alaeddine, F. Harb, M. Hamza, et al., Pharmacological regulation of cytochrome P450 metabolites of arachidonic acid attenuates cardiac injury in diabetic rats, Transl. Res. 235 (2021) 85-101.
[46]	X. Liu, J. Gao, J. Chen, et al., Identification of metabolic biomarkers in patients with type 2 diabetic coronary heart diseases based on metabolomic approach, Sci. Rep. 6 (2016), 30785.
[47]	A. Gnoni, S. Longo, G.V. Gnoni, et al., Carnitine in human muscle bioenergetics: can carnitine supplementation improve physical exercise? Molecules 25 (2020), 182.
[48]	N. Longo, M. Frigeni, M. Pasquali, Carnitine transport and fatty acid oxidation, Biochim. Biophys. Acta BBA Mol. Cell Res. 1863 (2016) 2422-2435.
[49]	L.A. Calo, E. Pagnin, P.A. Davis, et al., Antioxidant effect of l-carnitine and its short chain esters, Int. J. Cardiol. 107 (2006) 54-60.
[50]	J.N. van der Veen, S. Lingrell, R.P. da Silva, et al., The concentration of phosphatidylethanolamine in mitochondria can modulate ATP production and glucose metabolism in mice, Diabetes 63 (2014) 2620-2630.
[51]	X. Yang, J. Liang, L. Ding, et al., Phosphatidylserine synthase regulates cellular homeostasis through distinct metabolic mechanisms, PLoS Genet. 15 (2019), e1008548.
[52]	X. Xu, Z. Luo, Y. He, et al., Application of untargeted lipidomics based on UHPLC-high resolution tandem MS analysis to profile the lipid metabolic disturbances in the heart of diabetic cardiomyopathy mice, J. Pharm. Biomed. Anal. 190 (2020), 113525.
[53]	A. Vecchini, F. Del Rosso, L. Binaglia, et al., Molecular defects in sarcolemmal glycerophospholipid subclasses in diabetic cardiomyopathy, J. Mol. Cell. Cardiol. 32 (2000) 1061-1074.
[54]	E. Ramos-Tovar, P. Muriel, Molecular mechanisms that link oxidative stress, inflammation, and fibrosis in the liver, Antioxidants 9 (2020), 1279.
[55]	P. Cheresh, S.J. Kim, S. Tulasiram, et al., Oxidative stress and pulmonary fibrosis, Biochim. Biophys. Acta BBA Mol. Basis Dis. 1832 (2013) 1028-1040.
[56]	D.G. Hardie, AMP-activated protein kinase: an energy sensor that regulates all aspects of cell function, Genes Dev. 25 (2011) 1895-1908.
[57]	C. Lyons, H. Roche, Nutritional modulation of AMPK-impact upon metabolic-inflammation, Int. J. Mol. Sci. 19 (2018), 3092.
[58]	S. Bhattacharya, Reactive oxygen species and cellular defense system. Free Radic. Hum. Health Dis., Springer, New Delhi, 2015, pp. 17-29.
[59]	F.A. Matough, S.B. Budin, Z.A. Hamid, et al., The role of oxidative stress and antioxidants in diabetic complications, Sultan Qaboos Univ. Med. J. 12(2012)5-18.
[60]	R. Guzun, N. Timohhina, K. Tepp, et al., Systems bioenergetics of creatine kinase networks: physiological roles of creatine and phosphocreatine in regulation of cardiac cell function, Amino Acids 40 (2011) 1333-1348.
[61]	K.S. Kim, D.H. Oh, J.Y. Kim, et al., Taurine ameliorates hyperglycemia and dyslipidemia by reducing insulin resistance and leptin level in Otsuka Long-Evans Tokushima fatty (OLETF) rats with long-term diabetes, Exp. Mol. Med. 44 (2012) 665-673.
[62]	H.J. Pan, Y. Lin, Y.E. Chen, et al., Adverse hepatic and cardiac responses to rosiglitazone in a new mouse model of type 2 diabetes: Relation to dysregulated phosphatidylcholine metabolism, Vasc. Pharmacol. 45 (2006) 65-71.
[63]	L. Mandelker, Oxidative stress, free radicals, and cellular damage. Studies on Veterinary Medicine, Humana Press, Totowa, 2011, pp. 1–17.
[64]	Z. Xu, K.P. Patel, G.J. Rozanski, Metabolic basis of decreased transient outward K+ current in ventricular myocytes from diabetic rats, Am. J. Physiol. Heart Circ. Physiol. 271 (1996) H2190-H2196.
[65]	D.A. Cesario, R. Brar, K. Shivkumar, Alterations in ion channel physiology in diabetic cardiomyopathy, Endocrinol Metab. Clin. N. Am. 35 (2006) 601-610.
[66]	J.K. Kim, S.U. Park, A recent overview on the biological and pharmacological activities of ferulic acid, Excli J. 18 (2019) 132-138.
[67]	Y. Song, T. Wu, Q. Yang, et al., Ferulic acid alleviates the symptoms of diabetes in obese rats, J. Funct. Foods 9 (2014) 141-147.
[68]	S. Chowdhury, S. Ghosh, K. Rashid, et al., Deciphering the role of ferulic acid against streptozotocin-induced cellular stress in the cardiac tissue of diabetic rats, Food Chem. Toxicol. 97 (2016) 187-198.
[69]	S. Roy, S.K. Metya, S. Sannigrahi, et al., Treatment with ferulic acid to rats with streptozotocin-induced diabetes: effects on oxidative stress, pro-inflammatory cytokines, and apoptosis in the pancreatic β cell, Endocrine 44 (2013) 369-379.