Cardiomyocyte p38 MAPKα suppresses a heart-adipose tissue-neutrophil crosstalk in heart failure development.
Adipose Tissue
/ metabolism
Angiotensin II
/ metabolism
Animals
Cardiomegaly
/ metabolism
Fatty Acids
/ metabolism
Heart Failure
Inflammation
/ metabolism
Lipase
/ metabolism
Lipids
/ therapeutic use
Mice
Mice, Inbred C57BL
Myocytes, Cardiac
/ metabolism
Neutrophils
/ metabolism
Tamoxifen
/ metabolism
p38 Mitogen-Activated Protein Kinases
/ metabolism
Cardiac inflammation
Lipolysis
Metabolic dysfunction
Pressure overload
p38 MAPKα
Journal
Basic research in cardiology
ISSN: 1435-1803
Titre abrégé: Basic Res Cardiol
Pays: Germany
ID NLM: 0360342
Informations de publication
Date de publication:
07 10 2022
07 10 2022
Historique:
received:
08
07
2022
accepted:
18
09
2022
revised:
05
09
2022
entrez:
7
10
2022
pubmed:
8
10
2022
medline:
12
10
2022
Statut:
epublish
Résumé
Although p38 MAP Kinase α (p38 MAPKα) is generally accepted to play a central role in the cardiac stress response, to date its function in maladaptive cardiac hypertrophy is still not unambiguously defined. To induce a pathological type of cardiac hypertrophy we infused angiotensin II (AngII) for 2 days via osmotic mini pumps in control and tamoxifen-inducible, cardiomyocyte (CM)-specific p38 MAPKα KO mice (iCMp38αKO) and assessed cardiac function by echocardiography, complemented by transcriptomic, histological, and immune cell analysis. AngII treatment after inactivation of p38 MAPKα in CM results in left ventricular (LV) dilatation within 48 h (EDV: BL: 83.8 ± 22.5 µl, 48 h AngII: 109.7 ± 14.6 µl) and an ectopic lipid deposition in cardiomyocytes, reflecting a metabolic dysfunction in pressure overload (PO). This was accompanied by a concerted downregulation of transcripts for oxidative phosphorylation, TCA cycle, and fatty acid metabolism. Cardiac inflammation involving neutrophils, macrophages, B- and T-cells was significantly enhanced. Inhibition of adipose tissue lipolysis by the small molecule inhibitor of adipocytetriglyceride lipase (ATGL) Atglistatin reduced cardiac lipid accumulation by 70% and neutrophil infiltration by 30% and went along with an improved cardiac function. Direct targeting of neutrophils by means of anti Ly6G-antibody administration in vivo led to a reduced LV dilation in iCMp38αKO mice and an improved systolic function (EF: 39.27 ± 14%). Thus, adipose tissue lipolysis and CM lipid accumulation augmented cardiac inflammation in iCMp38αKO mice. Neutrophils, in particular, triggered the rapid left ventricular dilatation. We provide the first evidence that p38 MAPKα acts as an essential switch in cardiac adaptation to PO by mitigating metabolic dysfunction and inflammation. Moreover, we identified a heart-adipose tissue-immune cell crosstalk, which might serve as new therapeutic target in cardiac pathologies.
Identifiants
pubmed: 36205817
doi: 10.1007/s00395-022-00955-2
pii: 10.1007/s00395-022-00955-2
pmc: PMC9542472
doi:
Substances chimiques
Fatty Acids
0
Lipids
0
Tamoxifen
094ZI81Y45
Angiotensin II
11128-99-7
p38 Mitogen-Activated Protein Kinases
EC 2.7.11.24
Lipase
EC 3.1.1.3
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
48Subventions
Organisme : NIH HHS
ID : R01 DK101946
Pays : United States
Informations de copyright
© 2022. The Author(s).
Références
Bacmeister L, Schwarzl M, Warnke S, Stoffers B, Blankenberg S, Westermann D, Lindner D (2019) Inflammation and fibrosis in murine models of heart failure. Basic Res Cardiol 114:19. https://doi.org/10.1007/s00395-019-0722-5
doi: 10.1007/s00395-019-0722-5
Bolstad BM, Irizarry RA, Astrand M, Speed TP (2003) A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 19:185–193. https://doi.org/10.1093/bioinformatics/19.2.185
doi: 10.1093/bioinformatics/19.2.185
Bottermann K, Granade ME, Oenarto V, Fischer JW, Harris TE (2020) Atglistatin pretreatment preserves remote myocardium function following myocardial infarction. J Cardiovasc Pharmacol Ther. https://doi.org/10.1177/1074248420971113
doi: 10.1177/1074248420971113
Braz JC, Bueno OF, Liang Q, Wilkins BJ, Dai YS, Parsons S, Braunwart J, Glascock BJ, Klevitsky R, Kimball TF, Hewett TE, Molkentin JD (2003) Targeted inhibition of p38 MAPK promotes hypertrophic cardiomyopathy through upregulation of calcineurin-NFAT signaling. J Clin Invest 111:1475–1486. https://doi.org/10.1172/jci17295
doi: 10.1172/jci17295
Brenes-Castro D, Castillo EC, Vazquez-Garza E, Torre-Amione G, Garcia-Rivas G (2018) Temporal frame of immune cell infiltration during heart failure establishment: lessons from animal models. Int J Mol Sci. https://doi.org/10.3390/ijms19123719
doi: 10.3390/ijms19123719
Breslin WL, Strohacker K, Carpenter KC, Haviland DL, McFarlin BK (2013) Mouse blood monocytes: standardizing their identification and analysis using CD115. J Immunol Methods 390:1–8. https://doi.org/10.1016/j.jim.2011.03.005
doi: 10.1016/j.jim.2011.03.005
Ceddia RP, Collins S (2020) A compendium of G-protein-coupled receptors and cyclic nucleotide regulation of adipose tissue metabolism and energy expenditure. Clin Sci (Lond) 134:473–512. https://doi.org/10.1042/CS20190579
doi: 10.1042/CS20190579
Chen B, Frangogiannis NG (2016) Macrophages in the remodeling failing heart. Circ Res 119:776–778. https://doi.org/10.1161/circresaha.116.309624
doi: 10.1161/circresaha.116.309624
Chen L, Yang F, Chen X, Rao M, Zhang NN, Chen K, Deng H, Song JP, Hu SS (2017) Comprehensive myocardial proteogenomics profiling reveals C/EBPalpha as the key factor in the lipid storage of ARVC. J Proteome Res 16:2863–2876. https://doi.org/10.1021/acs.jproteome.7b00165
doi: 10.1021/acs.jproteome.7b00165
Cordero-Reyes AM, Youker KA, Trevino AR, Celis R, Hamilton DJ, Flores-Arredondo JH, Orrego CM, Bhimaraj A, Estep JD, Torre-Amione G (2016) Full expression of cardiomyopathy is partly dependent on B-cells: a pathway that involves cytokine activation, immunoglobulin deposition, and activation of apoptosis. J Am Heart Assoc. https://doi.org/10.1161/JAHA.115.002484
doi: 10.1161/JAHA.115.002484
Eguchi K, Manabe I, Oishi-Tanaka Y, Ohsugi M, Kono N, Ogata F, Yagi N, Ohto U, Kimoto M, Miyake K, Tobe K, Arai H, Kadowaki T, Nagai R (2012) Saturated fatty acid and TLR signaling link beta cell dysfunction and islet inflammation. Cell Metab 15:518–533. https://doi.org/10.1016/j.cmet.2012.01.023
doi: 10.1016/j.cmet.2012.01.023
Fischer TA, Ludwig S, Flory E, Gambaryan S, Singh K, Finn P, Pfeffer MA, Kelly RA, Pfeffer JM (2001) Activation of cardiac c-Jun NH(2)-terminal kinases and p38-mitogen-activated protein kinases with abrupt changes in hemodynamic load. Hypertension 37:1222–1228
doi: 10.1161/01.HYP.37.5.1222
Frangogiannis NG (2019) Cardiac fibrosis: cell biological mechanisms, molecular pathways and therapeutic opportunities. Mol Aspects Med 65:70–99. https://doi.org/10.1016/j.mam.2018.07.001
doi: 10.1016/j.mam.2018.07.001
Goldberg IJ, Trent CM, Schulze PC (2012) Lipid metabolism and toxicity in the heart. Cell Metab 15:805–812. https://doi.org/10.1016/j.cmet.2012.04.006
doi: 10.1016/j.cmet.2012.04.006
Han J, Molkentin JD (2000) Regulation of MEF2 by p38 MAPK and its implication in cardiomyocyte biology. Trends Cardiovasc Med 10:19–22. https://doi.org/10.1016/s1050-1738(00)00039-6
doi: 10.1016/s1050-1738(00)00039-6
Hayashida W, Kihara Y, Yasaka A, Inagaki K, Iwanaga Y, Sasayama S (2001) Stage-specific differential activation of mitogen-activated protein kinases in hypertrophied and failing rat hearts. J Mol Cell Cardiol 33:733–744. https://doi.org/10.1006/jmcc.2001.1341
doi: 10.1006/jmcc.2001.1341
Heinen A, Godecke S, Flogel U, Miklos D, Bottermann K, Spychala A, Godecke A (2021) 4-hydroxytamoxifen does not deteriorate cardiac function in cardiomyocyte-specific MerCreMer transgenic mice. Basic Res Cardiol 116:8. https://doi.org/10.1007/s00395-020-00841-9
doi: 10.1007/s00395-020-00841-9
Heinen A, Nederlof R, Panjwani P, Spychala A, Tschaidse T, Reffelt H, Boy J, Raupach A, Godecke S, Petzsch P, Kohrer K, Grandoch M, Petz A, Fischer JW, Alter C, Vasilevska J, Lang P, Godecke A (2019) IGF1 treatment improves cardiac remodeling after infarction by targeting myeloid cells. Mol Ther 27:46–58. https://doi.org/10.1016/j.ymthe.2018.10.020
doi: 10.1016/j.ymthe.2018.10.020
Heinen A, Raupach A, Behmenburg F, Holscher N, Flogel U, Kelm M, Kaisers W, Nederlof R, Huhn R, Godecke A (2018) Echocardiographic analysis of cardiac function after infarction in mice: validation of single-plane long-axis view measurements and the bi-plane Simpson method. Ultrasound Med Biol 44:1544–1555. https://doi.org/10.1016/j.ultrasmedbio.2018.03.020
doi: 10.1016/j.ultrasmedbio.2018.03.020
Heusch P, Canton M, Aker S, van de Sand A, Konietzka I, Rassaf T, Menazza S, Brodde OE, Di Lisa F, Heusch G, Schulz R (2010) The contribution of reactive oxygen species and p38 mitogen-activated protein kinase to myofilament oxidation and progression of heart failure in rabbits. Br J Pharmacol 160:1408–1416. https://doi.org/10.1111/j.1476-5381.2010.00793.x
doi: 10.1111/j.1476-5381.2010.00793.x
Jaeger BN, Donadieu J, Cognet C, Bernat C, Ordonez-Rueda D, Barlogis V, Mahlaoui N, Fenis A, Narni-Mancinelli E, Beaupain B, Bellanne-Chantelot C, Bajenoff M, Malissen B, Malissen M, Vivier E, Ugolini S (2012) Neutrophil depletion impairs natural killer cell maturation, function, and homeostasis. J Exp Med 209:565–580. https://doi.org/10.1084/jem.20111908
doi: 10.1084/jem.20111908
Jelenik T, Flogel U, Alvarez-Hernandez E, Scheiber D, Zweck E, Ding Z, Rothe M, Mastrototaro L, Kohlhaas V, Kotzka J, Knebel B, Muller-Wieland D, Moellendorf S, Godecke A, Kelm M, Westenfeld R, Roden M, Szendroedi J (2018) Insulin resistance and vulnerability to cardiac ischemia. Diabetes 67:2695–2702. https://doi.org/10.2337/db18-0449
doi: 10.2337/db18-0449
Kaiser RA, Bueno OF, Lips DJ, Doevendans PA, Jones F, Kimball TF, Molkentin JD (2004) Targeted inhibition of p38 mitogen-activated protein kinase antagonizes cardiac injury and cell death following ischemia-reperfusion in vivo. J Biol Chem 279:15524–15530. https://doi.org/10.1074/jbc.M313717200
doi: 10.1074/jbc.M313717200
Liang Q, Molkentin JD (2003) Redefining the roles of p38 and JNK signaling in cardiac hypertrophy: dichotomy between cultured myocytes and animal models. J Mol Cell Cardiol 35:1385–1394
doi: 10.1016/j.yjmcc.2003.10.001
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods 25:402–408. https://doi.org/10.1006/meth.2001.1262
doi: 10.1006/meth.2001.1262
Maik-Rachline G, Lifshits L, Seger R (2020) Nuclear P38: roles in physiological and pathological processes and regulation of nuclear translocation. Int J Mol Sci. https://doi.org/10.3390/ijms21176102
doi: 10.3390/ijms21176102
Maisel AS, Knowlton KU, Fowler P, Rearden A, Ziegler MG, Motulsky HJ, Insel PA, Michel MC (1990) Adrenergic control of circulating lymphocyte subpopulations. effects of congestive heart failure, dynamic exercise, and terbutaline treatment. J Clin Invest 85:462–467. https://doi.org/10.1172/JCI114460
doi: 10.1172/JCI114460
Mak TW, Hauck L, Grothe D, Billia F (2017) p53 regulates the cardiac transcriptome. Proc Natl Acad Sci USA 114:2331–2336. https://doi.org/10.1073/pnas.1621436114
doi: 10.1073/pnas.1621436114
Matyash V, Liebisch G, Kurzchalia TV, Shevchenko A, Schwudke D (2008) Lipid extraction by methyl-tert-butyl ether for high-throughput lipidomics. J Lipid Res 49:1137–1146. https://doi.org/10.1194/jlr.D700041-JLR200
doi: 10.1194/jlr.D700041-JLR200
Mayer N, Schweiger M, Romauch M, Grabner GF, Eichmann TO, Fuchs E, Ivkovic J, Heier C, Mrak I, Lass A, Hofler G, Fledelius C, Zechner R, Zimmermann R, Breinbauer R (2013) Development of small-molecule inhibitors targeting adipose triglyceride lipase. Nat Chem Biol 9:785–787. https://doi.org/10.1038/nchembio.1359
doi: 10.1038/nchembio.1359
Melloni C, Sprecher DL, Sarov-Blat L, Patel MR, Heitner JF, Hamm CW, Aylward P, Tanguay JF, DeWinter RJ, Marber MS, Lerman A, Hasselblad V, Granger CB, Newby LK (2012) The study of LoSmapimod treatment on inflammation and InfarCtSizE (SOLSTICE): design and rationale. Am Heart J 164(646–653):e643. https://doi.org/10.1016/j.ahj.2012.07.030
doi: 10.1016/j.ahj.2012.07.030
Michel MC, Li Y, Heusch G (2001) Mitogen-activated protein kinases in the heart. Naunyn Schmiedebergs Arch Pharmacol 363:245–266. https://doi.org/10.1007/s002100000363
doi: 10.1007/s002100000363
Mizote I, Yamaguchi O, Hikoso S, Takeda T, Taneike M, Oka T, Tamai T, Oyabu J, Matsumura Y, Nishida K, Komuro I, Hori M, Otsu K (2010) Activation of MTK1/MEKK4 induces cardiomyocyte death and heart failure. J Mol Cell Cardiol 48:302–309. https://doi.org/10.1016/j.yjmcc.2009.10.010
doi: 10.1016/j.yjmcc.2009.10.010
Molina CE, Jacquet E, Ponien P, Munoz-Guijosa C, Baczko I, Maier LS, Donzeau-Gouge P, Dobrev D, Fischmeister R, Garnier A (2018) Identification of optimal reference genes for transcriptomic analyses in normal and diseased human heart. Cardiovasc Res 114:247–258. https://doi.org/10.1093/cvr/cvx182
doi: 10.1093/cvr/cvx182
Molkentin JD, Bugg D, Ghearing N, Dorn LE, Kim P, Sargent MA, Gunaje J, Otsu K, Davis J (2017) Fibroblast-specific genetic manipulation of p38 mitogen-activated protein kinase in vivo reveals its central regulatory role in fibrosis. Circulation 136:549–561. https://doi.org/10.1161/CIRCULATIONAHA.116.026238
doi: 10.1161/CIRCULATIONAHA.116.026238
Naga Prasad SV, Esposito G, Mao L, Koch WJ, Rockman HA (2000) Gbetagamma-dependent phosphoinositide 3-kinase activation in hearts with in vivo pressure overload hypertrophy. J Biol Chem 275:4693–4698
doi: 10.1074/jbc.275.7.4693
Nishida K, Yamaguchi O, Hirotani S, Hikoso S, Higuchi Y, Watanabe T, Takeda T, Osuka S, Morita T, Kondoh G, Uno Y, Kashiwase K, Taniike M, Nakai A, Matsumura Y, Miyazaki J, Sudo T, Hongo K, Kusakari Y, Kurihara S, Chien KR, Takeda J, Hori M, Otsu K (2004) p38alpha mitogen-activated protein kinase plays a critical role in cardiomyocyte survival but not in cardiac hypertrophic growth in response to pressure overload. Mol Cell Biol 24:10611–10620. https://doi.org/10.1128/MCB.24.24.10611-10620.2004
doi: 10.1128/MCB.24.24.10611-10620.2004
O’Donoghue ML, Glaser R, Cavender MA, Aylward PE, Bonaca MP, Budaj A, Davies RY, Dellborg M, Fox KA, Gutierrez JA, Hamm C, Kiss RG, Kovar F, Kuder JF, Im KA, Lepore JJ, Lopez-Sendon JL, Ophuis TO, Parkhomenko A, Shannon JB, Spinar J, Tanguay JF, Ruda M, Steg PG, Theroux P, Wiviott SD, Laws I, Sabatine MS, Morrow DA, Investigators L-T (2016) Effect of losmapimod on cardiovascular outcomes in patients hospitalized with acute myocardial infarction: a randomized clinical trial. JAMA 315:1591–1599. https://doi.org/10.1001/jama.2016.3609
doi: 10.1001/jama.2016.3609
Otsu K, Yamashita N, Nishida K, Hirotani S, Yamaguchi O, Watanabe T, Hikoso S, Higuchi Y, Matsumura Y, Maruyama M, Sudo T, Osada H, Hori M (2003) Disruption of a single copy of the p38alpha MAP kinase gene leads to cardioprotection against ischemia-reperfusion. Biochem Biophys Res Commun 302:56–60
doi: 10.1016/S0006-291X(03)00096-2
Ozbalci C, Sachsenheimer T, Brugger B (2013) Quantitative analysis of cellular lipids by nano-electrospray ionization mass spectrometry. Methods Mol Biol 1033:3–20. https://doi.org/10.1007/978-1-62703-487-6_1
doi: 10.1007/978-1-62703-487-6_1
Parajuli N, Takahara S, Matsumura N, Kim TT, Ferdaoussi M, Migglautsch AK, Zechner R, Breinbauer R, Kershaw EE, Dyck JRB (2018) Atglistatin ameliorates functional decline in heart failure via adipocyte-specific inhibition of adipose triglyceride lipase. Am J Physiol Heart Circ Physiol 315:H879–H884. https://doi.org/10.1152/ajpheart.00308.2018
doi: 10.1152/ajpheart.00308.2018
Patel B, Bansal SS, Ismahil MA, Hamid T, Rokosh G, Mack M, Prabhu SD (2018) CCR2(+) monocyte-derived infiltrating macrophages are required for adverse cardiac remodeling during pressure overload. JACC Basic Transl Sci 3:230–244. https://doi.org/10.1016/j.jacbts.2017.12.006
doi: 10.1016/j.jacbts.2017.12.006
Pinto AR, Ilinykh A, Ivey MJ, Kuwabara JT, D’Antoni ML, Debuque R, Chandran A, Wang L, Arora K, Rosenthal NA, Tallquist MD (2016) Revisiting cardiac cellular composition. Circ Res 118:400–409. https://doi.org/10.1161/CIRCRESAHA.115.307778
doi: 10.1161/CIRCRESAHA.115.307778
Raje V, Ahern KW, Martinez BA, Howell NL, Oenarto V, Granade ME, Kim JW, Tundup S, Bottermann K, Godecke A, Keller SR, Kadl A, Bland ML, Harris TE (2020) Adipocyte lipolysis drives acute stress-induced insulin resistance. Sci Rep 10:18166. https://doi.org/10.1038/s41598-020-75321-0
doi: 10.1038/s41598-020-75321-0
Romero-Becerra R, Santamans AM, Folgueira C, Sabio G (2020) p38 MAPK pathway in the heart: new insights in health and disease. Int J Mol Sci. https://doi.org/10.3390/ijms21197412
doi: 10.3390/ijms21197412
Rose BA, Yokota T, Chintalgattu V, Ren S, Iruela-Arispe L, Khakoo AY, Minamisawa S, Wang Y (2017) Cardiac myocyte p38alpha kinase regulates angiogenesis via myocyte-endothelial cell cross-talk during stress-induced remodeling in the heart. J Biol Chem 292:12787–12800. https://doi.org/10.1074/jbc.M117.784553
doi: 10.1074/jbc.M117.784553
Salatzki J, Foryst-Ludwig A, Bentele K, Blumrich A, Smeir E, Ban Z, Brix S, Grune J, Beyhoff N, Klopfleisch R, Dunst S, Surma MA, Klose C, Rothe M, Heinzel FR, Krannich A, Kershaw EE, Beule D, Schulze PC, Marx N, Kintscher U (2018) Adipose tissue ATGL modifies the cardiac lipidome in pressure-overload-induced left ventricular failure. PLoS Genet 14:e1007171. https://doi.org/10.1371/journal.pgen.1007171
doi: 10.1371/journal.pgen.1007171
Sasse A, Wallich M, Ding Z, Goedecke A, Schrader J (2003) Coxsackie-and-adenovirus receptor mRNA expression in human heart failure. J Gene Med 5:876–882. https://doi.org/10.1002/jgm.411
doi: 10.1002/jgm.411
Schulz R, Aker S, Belosjorow S, Konietzka I, Rauen U, Heusch G (2003) Stress kinase phosphorylation is increased in pacing-induced heart failure in rabbits. Am J Physiol Heart Circ Physiol 285:H2084-2090. https://doi.org/10.1152/ajpheart.01038.2002
doi: 10.1152/ajpheart.01038.2002
Schulz R, Belosjorow S, Gres P, Jansen J, Michel MC, Heusch G (2002) p38 MAP kinase is a mediator of ischemic preconditioning in pigs. Cardiovasc Res 55:690–700. https://doi.org/10.1016/s0008-6363(02)00319-x
doi: 10.1016/s0008-6363(02)00319-x
Schulz R, Gres P, Skyschally A, Duschin A, Belosjorow S, Konietzka I, Heusch G (2003) Ischemic preconditioning preserves connexin 43 phosphorylation during sustained ischemia in pig hearts in vivo. FASEB J 17:1355–1357. https://doi.org/10.1096/fj.02-0975fje
doi: 10.1096/fj.02-0975fje
Schweiger M, Romauch M, Schreiber R, Grabner GF, Hutter S, Kotzbeck P, Benedikt P, Eichmann TO, Yamada S, Knittelfelder O, Diwoky C, Doler C, Mayer N, De Cecco W, Breinbauer R, Zimmermann R, Zechner R (2017) Pharmacological inhibition of adipose triglyceride lipase corrects high-fat diet-induced insulin resistance and hepatosteatosis in mice. Nat Commun 8:14859. https://doi.org/10.1038/ncomms14859
doi: 10.1038/ncomms14859
Sohal DS, Nghiem M, Crackower MA, Witt SA, Kimball TR, Tymitz KM, Penninger JM, Molkentin JD (2001) Temporally regulated and tissue-specific gene manipulations in the adult and embryonic heart using a tamoxifen-inducible Cre protein. Circ Res 89:20–25
doi: 10.1161/hh1301.092687
Subkhankulova T, Mitchell SA, Willis AE (2001) Internal ribosome entry segment-mediated initiation of c-Myc protein synthesis following genotoxic stress. Biochem J 359:183–192. https://doi.org/10.1042/0264-6021:3590183
doi: 10.1042/0264-6021:3590183
Takeishi Y, Huang Q, Abe J, Glassman M, Che W, Lee JD, Kawakatsu H, Lawrence EG, Hoit BD, Berk BC, Walsh RA (2001) Src and multiple MAP kinase activation in cardiac hypertrophy and congestive heart failure under chronic pressure-overload: comparison with acute mechanical stretch. J Mol Cell Cardiol 33:1637–1648. https://doi.org/10.1006/jmcc.2001.1427
doi: 10.1006/jmcc.2001.1427
Tenhunen O, Sarman B, Kerkela R, Szokodi I, Papp L, Toth M, Ruskoaho H (2004) Mitogen-activated protein kinases p38 and ERK 1/2 mediate the wall stress-induced activation of GATA-4 binding in adult heart. J Biol Chem 279:24852–24860. https://doi.org/10.1074/jbc.M314317200
doi: 10.1074/jbc.M314317200
Thomsen R, Solvsten CA, Linnet TE, Blechingberg J, Nielsen AL (2010) Analysis of qPCR data by converting exponentially related C
doi: 10.1142/s0219720010004963
van Berlo JH, Maillet M, Molkentin JD (2013) Signaling effectors underlying pathologic growth and remodeling of the heart. J Clin Invest 123:37–45. https://doi.org/10.1172/JCI62839
doi: 10.1172/JCI62839
Ventura JJ, Tenbaum S, Perdiguero E, Huth M, Guerra C, Barbacid M, Pasparakis M, Nebreda AR (2007) p38alpha MAP kinase is essential in lung stem and progenitor cell proliferation and differentiation. Nat Genet 39:750–758. https://doi.org/10.1038/ng2037
doi: 10.1038/ng2037
Verrou C, Zhang Y, Zurn C, Schamel WW, Reth M (1999) Comparison of the tamoxifen regulated chimeric Cre recombinases MerCreMer and CreMer. Biol Chem 380:1435–1438. https://doi.org/10.1515/BC.1999.184
doi: 10.1515/BC.1999.184
Wang Y, Sano S, Oshima K, Sano M, Watanabe Y, Katanasaka Y, Yura Y, Jung C, Anzai A, Swirski FK, Gokce N, Walsh K (2019) Wnt5a-mediated neutrophil recruitment has an obligatory role in pressure overload-induced cardiac dysfunction. Circulation 140:487–499. https://doi.org/10.1161/CIRCULATIONAHA.118.038820
doi: 10.1161/CIRCULATIONAHA.118.038820
Xia Y, Lee K, Li N, Corbett D, Mendoza L, Frangogiannis NG (2009) Characterization of the inflammatory and fibrotic response in a mouse model of cardiac pressure overload. Histochem Cell Biol 131:471–481. https://doi.org/10.1007/s00418-008-0541-5
doi: 10.1007/s00418-008-0541-5
Yokota T, Wang Y (2016) p38 MAP kinases in the heart. Gene 575:369–376. https://doi.org/10.1016/j.gene.2015.09.030
doi: 10.1016/j.gene.2015.09.030
Young SG, Zechner R (2013) Biochemistry and pathophysiology of intravascular and intracellular lipolysis. Genes Dev 27:459–484. https://doi.org/10.1101/gad.209296.112
doi: 10.1101/gad.209296.112
Zhang S, Ren J, Zhang CE, Treskov I, Wang Y, Muslin AJ (2003) Role of 14-3-3-mediated p38 mitogen-activated protein kinase inhibition in cardiac myocyte survival. Circ Res 93:1026–1028. https://doi.org/10.1161/01.RES.0000104084.88317.91
doi: 10.1161/01.RES.0000104084.88317.91
Zhang S, Weinheimer C, Courtois M, Kovacs A, Zhang CE, Cheng AM, Wang Y, Muslin AJ (2003) The role of the Grb2-p38 MAPK signaling pathway in cardiac hypertrophy and fibrosis. J Clin Invest 111:833–841. https://doi.org/10.1172/JCI16290
doi: 10.1172/JCI16290