Therapeutic Effects of Retinoic Acid in Lipopolysaccharide-Induced Cardiac Dysfunction: Network Pharmacology and Experimental Validation

References

• Qian M, Lou Y, Wang Y, et al. PICK1 deficiency exacerbates sepsis-associated acute lung injury and impairs glutathione synthesis via reduction of xCT. Free Radic Biol Med. 2018;1(18):23–34. doi:10.1016/j.freeradbiomed.2018.02.028
   Web of Science ®Google Scholar
• Fernando SM, Rochwerg B, Seely A. Clinical implications of the third international consensus definitions for sepsis and septic shock (Sepsis-3). CMAJ. 2018;36(190):E1058–9. doi:10.1503/cmaj.170149
   Web of Science ®Google Scholar
• Hollenberg SM, Singer M. Pathophysiology of sepsis-induced cardiomyopathy. Nat Rev Cardiol. 2021;6(18):424–434. doi:10.1038/s41569-020-00492-2
   Web of Science ®Google Scholar
• Weiss SL, Cvijanovich NZ, Allen GL, et al. Differential expression of the nuclear-encoded mitochondrial transcriptome in pediatric septic shock. Crit Care. 2014;6(18):623. doi:10.1186/s13054-014-0623-9
   Web of Science ®Google Scholar
• Meyer NJ. Finding a needle in the haystack: leveraging bioinformatics to identify a functional genetic risk factor for sepsis death. Crit Care Med. 2015;1(43):242–243. doi:10.1097/CCM.0000000000000664
   Web of Science ®Google Scholar
• Burnham KL, Davenport EE, Radhakrishnan J, et al. Shared and distinct aspects of the sepsis transcriptomic response to fecal peritonitis and pneumonia. Am J Respir Crit Care Med. 2017;3(196):328–339. doi:10.1164/rccm.201608-1685OC
   Web of Science ®Google Scholar
• Scicluna BP, van Vught LA, Zwinderman AH, et al. Classification of patients with sepsis according to blood genomic endotype: a prospective cohort study. Lancet Respir Med. 2017;10(5):816–826.
   Web of Science ®Google Scholar
• Jia L, Wang Y, Wang Y, et al. Heme oxygenase-1 in macrophages drives septic cardiac dysfunction via suppressing lysosomal degradation of inducible nitric oxide synthase. Circ Res. 2018;11(122):1532–1544. doi:10.1161/CIRCRESAHA.118.312910
   Web of Science ®Google Scholar
• Smeding L, Plotz FB, Groeneveld AB, et al. Structural changes of the heart during severe sepsis or septic shock. Shock. 2012;5(37):449–456. doi:10.1097/SHK.0b013e31824c3238
   Web of Science ®Google Scholar
• Vanasco V, Saez T, Magnani ND, et al. Cardiac mitochondrial biogenesis in endotoxemia is not accompanied by mitochondrial function recovery. Free Radic Biol Med. 2014;77:1–9. doi:10.1016/j.freeradbiomed.2014.08.009
   PubMed Web of Science ®Google Scholar
• Wagner S, Schurmann S, Hein S, et al. Septic cardiomyopathy in rat LPS-induced endotoxemia: relative contribution of cellular diastolic Ca(2+) removal pathways, myofibrillar biomechanics properties and action of the cardiotonic drug levosimendan. Basic Res Cardiol. 2015;5(110):507. doi:10.1007/s00395-015-0507-4
   Web of Science ®Google Scholar
• Schilling J, Lai L, Sambandam N, et al. Toll-like receptor-mediated inflammatory signaling reprograms cardiac energy metabolism by repressing peroxisome proliferator-activated receptor gamma coactivator-1 signaling. Circ Heart Fail. 2011;4(4):474–482. doi:10.1161/CIRCHEARTFAILURE.110.959833
   PubMed Web of Science ®Google Scholar
• Ziolo MT, Katoh H, Bers DM. Expression of inducible nitric oxide synthase depresses beta-adrenergic-stimulated calcium release from the sarcoplasmic reticulum in intact ventricular myocytes. Circulation. 2001;24(104):2961–2966. doi:10.1161/hc4901.100379
   Web of Science ®Google Scholar
• Alvarez S, Vico T, Vanasco V. Cardiac dysfunction, mitochondrial architecture, energy production, and inflammatory pathways: interrelated aspects in endotoxemia and sepsis. Int J Biochem Cell Biol. 2016;81(Pt B(81)):307–314. doi:10.1016/j.biocel.2016.07.032
   PubMed Web of Science ®Google Scholar
• Nurrahmah QI, Madhyastha R, Madhyastha H, et al. Retinoic acid abrogates LPS-induced inflammatory response via negative regulation of NF-kappa B/miR-21 signaling. Immunopharmacol Immunotoxicol. 2021;3(43):299–308. doi:10.1080/08923973.2021.1902348
   Web of Science ®Google Scholar
• Li S, Lei Y, Lei J, et al. All-trans retinoic acid promotes macrophage phagocytosis and decreases inflammation via inhibiting CD14/TLR4 in acute lung injury. Mol Med Rep. 2021;24(6). doi:10.3892/mmr.2021.12508
   Web of Science ®Google Scholar
• Austenaa LM, Carlsen H, Hollung K, et al. Retinoic acid dampens LPS-induced NF-kappaB activity: results from human monoblasts and in vivo imaging of NF-kappaB reporter mice. J Nutr Biochem. 2009;9(20):726–734. doi:10.1016/j.jnutbio.2008.07.002
   Web of Science ®Google Scholar
• Martire-Greco D, Landoni VI, Chiarella P, et al. all-trans-retinoic acid improves immunocompetence in a murine model of lipopolysaccharide-induced immunosuppression. Clin Sci. 2014;5(126):355–365. doi:10.1042/CS20130236
   Web of Science ®Google Scholar
• Tang M, Xie X, Yi P, et al. Integrating network pharmacology with molecular docking to unravel the active compounds and potential mechanism of simiao pill treating rheumatoid arthritis. Evid Based Complement Alternat Med. 2020;2020:5786053. doi:10.1155/2020/5786053
   PubMed Web of Science ®Google Scholar
• Liu Z, Huo JH, Dong WT, et al. A study based on metabolomics, network pharmacology, and experimental verification to explore the mechanism of qinbaiqingfei concentrated pills in the treatment of mycoplasma pneumonia. Front Pharmacol. 2021;12:761883. doi:10.3389/fphar.2021.761883
   PubMed Web of Science ®Google Scholar
• Hopkins AL. Network pharmacology: the next paradigm in drug discovery. Nat Chem Biol. 2008;11(4):682–690. doi:10.1038/nchembio.118
   Web of Science ®Google Scholar
• Recanatini M, Cabrelle C. Drug research meets network science: where are we? J Med Chem. 2020;16(63):8653–8666. doi:10.1021/acs.jmedchem.9b01989
   Web of Science ®Google Scholar
• Hopkins AL. Network pharmacology. Nat Biotechnol. 2007;10(25):1110–1111. doi:10.1038/nbt1007-1110
   Web of Science ®Google Scholar
• Tao W, Xu X, Wang X, et al. Network pharmacology-based prediction of the active ingredients and potential targets of Chinese herbal Radix Curcumae formula for application to cardiovascular disease. J Ethnopharmacol. 2013;1(145):1–10. doi:10.1016/j.jep.2012.09.051
   Web of Science ®Google Scholar
• Fang J, Liu C, Wang Q, et al. In silico polypharmacology of natural products. Brief Bioinform. 2018;6(19):1153–1171. doi:10.1093/bib/bbx045
   Web of Science ®Google Scholar
• Barrett T, Wilhite SE, Ledoux P, et al. NCBI GEO: archive for functional genomics data sets–update. Nucleic Acids Res. 2013;41(Database issue(41)):D991–5. doi:10.1093/nar/gks1193
   PubMed Web of Science ®Google Scholar
• Ritchie ME, Phipson B, Wu D, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;7(43):e47. doi:10.1093/nar/gkv007
   Web of Science ®Google Scholar
• Kim S, Chen J, Cheng T, et al. PubChem in 2021: new data content and improved web interfaces. Nucleic Acids Res. 2021;49(D1(49)):D1388–95. doi:10.1093/nar/gkaa971
   PubMed Web of Science ®Google Scholar
• Szklarczyk D, Santos A, von Mering C, et al. STITCH 5: augmenting protein-chemical interaction networks with tissue and affinity data. Nucleic Acids Res. 2016;44(D1(44)):D380–4. doi:10.1093/nar/gkv1277
   PubMed Web of Science ®Google Scholar
• Ashburner M, Ball CA, Blake JA, et al. Gene ontology: tool for the unification of biology. The gene ontology consortium. Nat Genet. 2000;1(25):25–29. doi:10.1038/75556
   Web of Science ®Google Scholar
• Li S, Li L, Meng X, et al. DREAM: a database of experimentally supported protein-coding RNAs and drug associations in human cancer. Mol Cancer. 2021;1(20):148. doi:10.1186/s12943-021-01436-1
   Web of Science ®Google Scholar
• Altermann E, Klaenhammer TR. PathwayVoyager: pathway mapping using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. BMC Genom. 2005;6:60. doi:10.1186/1471-2164-6-60
   PubMed Web of Science ®Google Scholar
• Backes C, Keller A, Kuentzer J, et al. GeneTrail–advanced gene set enrichment analysis. Nucleic Acids Res. 2007;35(Web Server issue(35)):W186–92. doi:10.1093/nar/gkm323
   PubMed Web of Science ®Google Scholar
• Szklarczyk D, Gable AL, Lyon D, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2019;47(D1(47)):D607–13. doi:10.1093/nar/gky1131
   PubMed Web of Science ®Google Scholar
• Shannon P, Markiel A, Ozier O, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;11(13):2498–2504. doi:10.1101/gr.1239303
   Web of Science ®Google Scholar
• Liu C, He D, Zhao Q. Licoricidin improves neurological dysfunction after traumatic brain injury in mice via regulating FoxO3/Wnt/beta-catenin pathway. J Nat Med. 2020;4(74):767–776. doi:10.1007/s11418-020-01434-5
   Web of Science ®Google Scholar
• Chen Y, Tang J, Zhang Y, et al. Astaxanthin alleviates gestational diabetes mellitus in mice through suppression of oxidative stress. Naunyn Schmiedebergs Arch Pharmacol. 2020;393(12):2517-2527. doi:10.1007/s00210-020-01861-x
   Google Scholar
• Deng C, Zhang B, Zhang S, et al. Low nanomolar concentrations of Cucurbitacin-I induces G2/M phase arrest and apoptosis by perturbing redox homeostasis in gastric cancer cells in vitro and in vivo. Cell Death Dis. 2016;7:e2106. doi:10.1038/cddis.2016.13
   PubMed Web of Science ®Google Scholar
• Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;8(315):801–810. doi:10.1001/jama.2016.0287
   Web of Science ®Google Scholar
• Drosatos K, Lymperopoulos A, Kennel PJ, et al. Pathophysiology of sepsis-related cardiac dysfunction: driven by inflammation, energy mismanagement, or both? Curr Heart Fail Rep. 2015;2(12):130–140. doi:10.1007/s11897-014-0247-z
   Google Scholar
• Rossol M, Heine H, Meusch U, et al. LPS-induced cytokine production in human monocytes and macrophages. Crit Rev Immunol. 2011;5(31):379–446. doi:10.1615/critrevimmunol.v31.i5.20
   Web of Science ®Google Scholar
• Drott PW, Meurling S, Kulander L, et al. Effects of vitamin A on endotoxaemia in rats. Eur J Surg. 1991;10(157):565–569.
   Google Scholar
• Slade E, Tamber PS, Vincent JL. The surviving sepsis campaign: raising awareness to reduce mortality. Crit Care. 2003;1(7):1–2. doi:10.1186/cc1876
   Web of Science ®Google Scholar
• Carcillo JA. Reducing the global burden of sepsis in infants and children: a clinical practice research agenda. Pediatr Crit Care Med. 2005;3(Suppl(6)):S157–64. doi:10.1097/01.PCC.0000161574.36857.CA
   Google Scholar
• Eriksson M, Lundkvist K, Drott P, et al. Beneficial effects of pre-treatment with vitamin A on cardiac and pulmonary functions in endotoxaemic pigs. Acta Anaesthesiol Scand. 1996;5(40):538–548. doi:10.1111/j.1399-6576.1996.tb04485.x
   Web of Science ®Google Scholar
• Kibble M, Saarinen N, Tang J, et al. Network pharmacology applications to map the unexplored target space and therapeutic potential of natural products. Nat Prod Rep. 2015;8(32):1249–1266. doi:10.1039/c5np00005j
   Web of Science ®Google Scholar
• Wahli W, Michalik L. PPARs at the crossroads of lipid signaling and inflammation. Trends Endocrinol Metab. 2012;7(23):351–363. doi:10.1016/j.tem.2012.05.001
   Web of Science ®Google Scholar
• Choo J, Lee Y, Yan XJ, et al. A Novel Peroxisome Proliferator-activated Receptor (PPAR) gamma agonist 2-hydroxyethyl 5-chloro-4,5-didehydrojasmonate exerts anti-inflammatory effects in colitis. J Biol Chem. 2015;42(290):25609–25619. doi:10.1074/jbc.M115.673046
   Web of Science ®Google Scholar
• Kilu W, Merk D, Steinhilber D, et al. Heterodimer formation with retinoic acid receptor RXRalpha modulates coactivator recruitment by peroxisome proliferator-activated receptor PPARgamma. J Biol Chem. 2021;1(297):100814. doi:10.1016/j.jbc.2021.100814
   Web of Science ®Google Scholar
• Feingold K, Kim MS, Shigenaga J, et al. Altered expression of nuclear hormone receptors and coactivators in mouse heart during the acute-phase response. Am J Physiol Endocrinol Metab. 2004;2(286):E201–7. doi:10.1152/ajpendo.00205.2003
   Web of Science ®Google Scholar
• Standage SW, Waworuntu RL, Delaney MA, et al. Nonhematopoietic peroxisome proliferator-activated receptor-alpha protects against cardiac injury and enhances survival in experimental polymicrobial sepsis. Crit Care Med. 2016;8(44):e594–603. doi:10.1097/CCM.0000000000001585
   Web of Science ®Google Scholar
• Amoutzias GD, Pichler EE, Mian N, et al. A protein interaction atlas for the nuclear receptors: properties and quality of a hub-based dimerisation network. BMC Syst Biol. 2007;1:34. doi:10.1186/1752-0509-1-34
   PubMed Web of Science ®Google Scholar
• Jamsa J, Huotari V, Savolainen ER, et al. Kinetics of leukocyte CD11b and CD64 expression in severe sepsis and non-infectious critical care patients. Acta Anaesthesiol Scand. 2015;7(59):881–891. doi:10.1111/aas.12515
   Web of Science ®Google Scholar
• Sheneef A, Mohamed T, Boraey NF, et al. Neutrophil CD11b, CD64 and lipocalin-2: early diagnostic markers of neonatal sepsis. Egypt J Immunol. 2017;1(24):29–36.
   Google Scholar
• Zhou H, Li Y, Gui H, et al. Antagonism of integrin CD11b affords protection against endotoxin shock and polymicrobial sepsis via attenuation of HMGB1 nucleocytoplasmic translocation and extracellular release. J Immunol. 2018;5(200):1771–1780. doi:10.4049/jimmunol.1701285
   Web of Science ®Google Scholar
• Hoshi M, Osawa Y, Ito H, et al. Blockade of indoleamine 2,3-dioxygenase reduces mortality from peritonitis and sepsis in mice by regulating functions of CD11b+ peritoneal cells. Infect Immun. 2014;11(82):4487–4495. doi:10.1128/IAI.02113-14
   Web of Science ®Google Scholar
• Sim H, Jeong D, Kim HI, et al. CD11b deficiency exacerbates methicillin-resistant staphylococcus aureus-induced sepsis by upregulating inflammatory responses of macrophages. Immune Netw. 2021;21(2):e13. doi:10.4110/in.2021.21.e13
   PubMed Web of Science ®Google Scholar
• Duriancik DM, Hoag KA. Vitamin A deficiency alters splenic dendritic cell subsets and increases CD8(+) Gr-1(+) memory T lymphocytes in C57BL/6J mice. Cell Immunol. 2010;2(265):156–163. doi:10.1016/j.cellimm.2010.08.006
   Web of Science ®Google Scholar
• Gatto D, Wood K, Caminschi I, et al. The chemotactic receptor EBI2 regulates the homeostasis, localization and immunological function of splenic dendritic cells. Nat Immunol. 2013;5(14):446–453. doi:10.1038/ni.2555
   Web of Science ®Google Scholar
• Beijer MR, Molenaar R, Goverse G, et al. A crucial role for retinoic acid in the development of Notch-dependent murine splenic CD8 − CD4 − and CD4 + dendritic cells. Eur J Immunol. 2013;6(43):1608–1616. doi:10.1002/eji.201343325
   Web of Science ®Google Scholar
• Yi T, Cyster JG. EBI2-mediated bridging channel positioning supports splenic dendritic cell homeostasis and particulate antigen capture. Elife. 2013;2:e757. doi:10.7554/eLife.00757
   Web of Science ®Google Scholar
• Lush CW, Cepinskas G, Kvietys PR. LPS tolerance in human endothelial cells: reduced PMN adhesion, E-selectin expression, and NF-kappaB mobilization. Am J Physiol Heart Circ Physiol. 2000;3(278):H853–61. doi:10.1152/ajpheart.2000.278.3.H853
   Web of Science ®Google Scholar
• Ulbrich H, Eriksson EE, Lindbom L. Leukocyte and endothelial cell adhesion molecules as targets for therapeutic interventions in inflammatory disease. Trends Pharmacol Sci. 2003;12(24):640–647. doi:10.1016/j.tips.2003.10.004
   Web of Science ®Google Scholar
• van Meurs M, Wulfert FM, Knol AJ, et al. Early organ-specific endothelial activation during hemorrhagic shock and resuscitation. Shock. 2008;2(29):291–299. doi:10.1097/SHK.0b013e318145a7c1
   Web of Science ®Google Scholar
• Matsukawa A, Lukacs NW, Hogaboam CM, et al. Mice genetically lacking endothelial selectins are resistant to the lethality in septic peritonitis. Exp Mol Pathol. 2002;1(72):68–76. doi:10.1006/exmp.2001.2416
   Web of Science ®Google Scholar
• Dauphinee SM, Karsan A. Lipopolysaccharide signaling in endothelial cells. Lab Invest. 2006;1(86):9–22. doi:10.1038/labinvest.3700366
   Web of Science ®Google Scholar
• Su CM, Cheng HH, Tsai TC, et al. Elevated serum vascular cell adhesion molecule-1 is associated with septic encephalopathy in adult community-onset severe sepsis patients. Biomed Res Int. 2014;2014:598762. doi:10.1155/2014/598762
   PubMed Web of Science ®Google Scholar
• Moser J, Heeringa P, Jongman RM, et al. Intracellular RIG-I signaling regulates TLR4-independent endothelial inflammatory responses to endotoxin. J Immunol. 2016;11(196):4681–4691. doi:10.4049/jimmunol.1501819
   Web of Science ®Google Scholar
• Gille J, Paxton LL, Lawley TJ, et al. Retinoic acid inhibits the regulated expression of vascular cell adhesion molecule-1 by cultured dermal microvascular endothelial cells. J Clin Invest. 1997;3(99):492–500. doi:10.1172/JCI119184
   Web of Science ®Google Scholar
• Lembo G, Rockman HA, Hunter JJ, et al. Elevated blood pressure and enhanced myocardial contractility in mice with severe IGF-1 deficiency. J Clin Invest. 1996;11(98):2648–2655. doi:10.1172/JCI119086
   Web of Science ®Google Scholar
• Ahasic AM, Tejera P, Wei Y, et al. Predictors of circulating insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 in critical illness. Crit Care Med. 2015;12(43):2651–2659. doi:10.1097/CCM.0000000000001314
   Web of Science ®Google Scholar
• Barabutis N. Growth hormone releasing hormone in endothelial barrier function. Trends Endocrinol Metab. 2021;6(32):338–340. doi:10.1016/j.tem.2021.03.001
   Web of Science ®Google Scholar
• Ungvari Z, Csiszar A. The emerging role of IGF-1 deficiency in cardiovascular aging: recent advances. J Gerontol a Biol Sci Med Sci. 2012;6(67):599–610. doi:10.1093/gerona/gls072
   Web of Science ®Google Scholar
• Wahlander H, Isgaard J, Jennische E, et al. Left ventricular insulin-like growth factor I increases in early renal hypertension. Hypertension. 1992;1(19):25–32. doi:10.1161/01.hyp.19.1.25
   Web of Science ®Google Scholar
• He H, Chang X, Gao J, et al. Salidroside mitigates sepsis-induced myocarditis in rats by regulating IGF-1/PI3K/Akt/GSK-3beta signaling. Inflammation. 2015;6(38):2178–2184. doi:10.1007/s10753-015-0200-7
   Web of Science ®Google Scholar
• Donohue TJ, Dworkin LD, Lango MN, et al. Induction of myocardial insulin-like growth factor-I gene expression in left ventricular hypertrophy. Circulation. 1994;2(89):799–809. doi:10.1161/01.cir.89.2.799
   Web of Science ®Google Scholar
• Shim JH, Shin DW, Lee TR, et al. The retinoic acid-induced up-regulation of insulin-like growth factor 1 and 2 is associated with prolidase-dependent collagen synthesis in UVA-irradiated human dermal equivalents. J Dermatol Sci. 2012;1(66):51–59. doi:10.1016/j.jdermsci.2011.12.008
   Web of Science ®Google Scholar
• Vanhaesebroeck B, Stephens L, Hawkins P. PI3K signalling: the path to discovery and understanding. Nat Rev Mol Cell Biol. 2012;3(13):195–203. doi:10.1038/nrm3290
   Web of Science ®Google Scholar
• Hamzehzadeh L, Atkin SL, Majeed M, et al. The versatile role of curcumin in cancer prevention and treatment: a focus on PI3K/AKT pathway. J Cell Physiol. 2018;10(233):6530–6537. doi:10.1002/jcp.26620
   Web of Science ®Google Scholar
• Franke TF, Kaplan DR, Cantley LC. PI3K: downstream AKTion blocks apoptosis. Cell. 1997;4(88):435–437. doi:10.1016/s0092-8674(00)81883-8
   Web of Science ®Google Scholar
• Matsui T, Tao J, Del MF, et al. Akt activation preserves cardiac function and prevents injury after transient cardiac ischemia in vivo. Circulation. 2001;3(104):330–335. doi:10.1161/01.cir.104.3.330
   Google Scholar
• Matsui T, Li L, Wu JC, et al. Phenotypic spectrum caused by transgenic overexpression of activated Akt in the heart. J Biol Chem. 2002;25(277):22896–22901. doi:10.1074/jbc.M200347200
   Web of Science ®Google Scholar
• Debosch B, Sambandam N, Weinheimer C, et al. Akt2 regulates cardiac metabolism and cardiomyocyte survival. J Biol Chem. 2006;43(281):32841–32851. doi:10.1074/jbc.M513087200
   Web of Science ®Google Scholar
• Roberts DJ, Tan-Sah VP, Smith JM, et al. Akt phosphorylates HK-II at Thr-473 and increases mitochondrial HK-II association to protect cardiomyocytes. J Biol Chem. 2013;33(288):23798–23806. doi:10.1074/jbc.M113.482026
   Web of Science ®Google Scholar