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Aging and disease    2020, Vol. 11 Issue (4) : 916-926     DOI: 10.14336/AD.2020.0401
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p300 in Cardiac Development and Accelerated Cardiac Aging
Ghosh Asish K*
Feinberg Cardiovascular and Renal Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA
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The heart is the first functional organ that develops during embryonic development. While a heartbeat indicates life, cessation of a heartbeat signals the end of life. Heart disease, due either to congenital defects or to acquired dysfunctions in adulthood, remains the leading cause of death worldwide. Epigenetics plays a key role in both embryonic heart development and heart disease in adults. Stress-induced vascular injury activates pathways involved in pathogenesis of accelerated cardiac aging that includes cellular dysfunction, pathological cardiac hypertrophy, diabetic cardiomyopathy, cardiac matrix remodeling, cardiac dysfunction and heart failure. Acetyltransferase p300 (p300), a major epigenetic regulator, plays a pivotal role in heart development during embryogenesis, as deficiency or abnormal expression of p300 leads to embryonic death at early gestation periods due to deformation of the heart and neural tube. Acetyltransferase p300 controls heart development through histone acetylation-mediated chromatin remodeling and transcriptional regulation of genes required for cardiac development. In adult hearts, p300 is differentially expressed in different chambers and epigenetically controls cardiac gene expression. Deregulation of p300, in response to prohypertrophic and profibrogenic stress signals, is associated with increased recruitment of p300 to several genes including transcription factors, increased acetylation of specific lysines in histones and transcription factors, altered chromatin organization, and increased hypertrophic and fibrogenic gene expression. Cardiac hypertrophy and myocardial fibrogenesis are common pathological manifestations of several stress-induced accelerated cardiac aging-related pathologies, including high blood pressure-induced or environmentally induced cardiac hypertrophy, myocardial infarction, diabetes-induced cardiomyopathy, and heart failure. Numerous studies using cellular and animal models clearly indicate that pharmacologic or genetic normalization of p300 activity has the potential to prevent or halt the progression of cardiac aging pathologies. Based on these preclinical studies, development of safe, non-toxic, small molecule inhibitors/epidrugs targeting p300 is an ideal approach to control accelerated cardiac aging-related deaths worldwide.

Keywords heart development      cardiac aging      epigenetics      acetyltransferase p300      extracellular matrix      air-pollutant      hypertension      hypertrophy      fibrosis      heart failure      epidrugs     
Corresponding Authors: Ghosh Asish K   
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These authors contributed equally to this work.

Just Accepted Date: 17 April 2020   Issue Date: 30 July 2020
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Ghosh Asish K
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Ghosh Asish K. p300 in Cardiac Development and Accelerated Cardiac Aging[J]. Aging and disease, 2020, 11(4): 916-926.
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Figure 1.  Acetyltransferase p300 in cardiac development and accelerated cardiac aging. Physiological level of p300 plays a significant role in heart development: defects in heart development in p300 null mouse embryos and significant percentage of heterozygous mouse embryos. Stresses like hypertension-induced or diabetes-induced or vascular injury-induced elevated level of p300 significantly contributes to accelerated cardiac aging pathologies viz. pathological cardiac hypertrophy, diabetic cardiomyopathy, systolic and diastolic dysfunction, failing hearts with myocardial fibrosis.
Figure 2.  Acetyltransferase p300 (p300), Acetylated histone 3 lysine 9 (AcH3K9) and Type I collagen (fibrosis) are elevated in hypertensive murine hearts. (A) Elevated expression of p300 in Angiotensin II-induced hypertensive murine hearts and its correlation with increased expression of acetylated histone H3 lysine 9 residue (AcH3K9) and elevated levels of ventricular fibrosis. (B) Model depicting the epigenetic regulation of accelerated cardiac aging by deregulated p300 and as a druggable target for accelerated cardiac aging therapy. TF; Transcription factor; MI: myocardial infarction. Inhibitors and modulators of p300 activity used in cell and animal models to suppress the acetyltransferase activity of p300 in hearts and accelerated cardiac aging pathologies: curcumin [24,59,61,63,66]; L002 [22,23]; C646 [22,23]; resveratrol [64,65].
[1] Ji RP, Phoon CK, Aristizábal O, McGrath KE, Palis J, Turnbull DH (2003). Onset of cardiac function during early mouse embryogenesis coincides with entry of primitive erythroblasts into the embryo proper. Circ Res, 92:133-35.
[2] Franci G, Miceli M, Altucci L (2010). Targeting epigenetic networks with polypharmacology: a new avenue to tackle cancer. Epigenomics, 2:731-42.
[3] Yee S, Branton P (1985). Detection of cellular proteins associated with human adenovirus type 5 early region 1A polypeptides. Virology, 147:142-53.
[4] Harlow EP, Whyte BR, Franza Jr, Schley C (1986). Association of adenovirus early-region 1A proteins with cellular polypeptides. Mol Cell Biol, 6:1579-89.
[5] Stein RW, Corrigan M, Yaciuk P, Whelan J, Moran E (1990). Analysis of ElA-Mediated Growth Regulation Functions: Binding of the 300-Kilodalton Cellular Product Correlates with ElA Enhancer Repression Function and DNA Synthesis-Inducing Activity. J Virol, 64:4421-27.
[6] Hasegawa K, Meyers MB, Kitsis RN (1997). Transcriptional coactivator p300 stimulates cell type-specific gene expression in cardiac myocytes. J Biol Chem, 272:20049-54.
[7] Eckner R, Yao TP, Oldread E, Livingston DM (1996). Interaction and functional collaboration of p300/CBP and bHLH proteins in muscle and B-cell differentiation. Genes Dev, 10:2478-90.
[8] Eckner R, Ewen ME, Newsome D, et al. (1994). Molecular cloning and functional analysis of the adenovirus E1A-associated 300-kD protein (p300) reveals a protein with properties of a transcriptional adaptor. Genes Dev, 8:869-84.
[9] Ogryzko VV, Schiltz RL, Russanova V, Howard BH, Nakatani Y (1996). The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell, 87:953-59.
[10] Chan HM, La Thangue NB (2001). p300/CBP proteins: HATs for transcriptional bridges and scaffolds. J Cell Sci, 114:2363-73.
[11] Shi Y, Mello C (1998). A CBP/p300 homolog specifies multiple differentiation pathways in Caenorhabditis elegans. Genes & Dev, 12: 943-55.
[12] Chiang WC, Tishkoff DX, Yang B, et al. (2012). C. elegans SIRT6/7 homolog SIR-2.4 promotes DAF-16 relocalization and function during stress. PLoS Genet, 8:e1002948.
[13] Gonçalves S, Patat J, Guida MC, Lachaussée N, et al. (2018). A homozygous KAT2B variant modulates the clinical phenotype of ADD3 deficiency in humans and flies. PLoS Genet, 14:e1007386.
[14] Yao TP, Oh SP, Fuchs M, Zhou ND, Ch'ng LE, Newsome D, Bronson RT, Li E, Livingston DM, Eckner R (1998). Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300. Cell, 93:361-72.
[15] Roelfsema JH, White SJ, Ariyürek Y, et al. (2005). Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations in both the CBP and EP300 genes cause disease. Am J Hum Genet, 76:572-80.
[16] Hamilton MJ, Newbury-Ecob R, Holder-Espinasse M, et al. (2016). DDD Study. Rubinstein-Taybi syndrome type 2: report of nine new cases that extend the phenotypic and genotypic spectrum. Clin Dysmorphol, 25:135-45.
[17] López M, Seidel V, Santibáñez P, Cervera-Acedo C, Castro-de Castro P, Domínguez-Garrido E (2016). First case report of inherited Rubinstein-Taybi syndrome associated with a novel EP300 variant. BMC Med Genet, 17:97.
[18] Iyer NG, Ozdag H, Caldas C (2004). p300/CBP and cancer. Oncogene, 23:4225-31.
[19] Shen H, Laird PW (2013). Interplay between the cancer genome and epigenome. Cell, 153:38-55.
[20] Ghosh AK, Bhattacharyya S, Lafyatis R, Farina G, Yu J, Thimmapaya B, Wei J, Varga J (2013). p300 is elevated in systemic sclerosis and its expression is positively regulated by TGF-β: epigenetic feed-forward amplification of fibrosis. J Invest Dermatol, 133:1302-10.
[21] Zeng Z, Cheng S, Chen H, Li Q, Hu Y, Wang Q, Zhu X, Wang J (2017). Activation and overexpression of Sirt1 attenuates lung fibrosis via p300. Biochem Biophys Res Commun, 486:1021-26.
[22] Rai R, Verma SK, Kim D, Ramirez V, Lux E, Li C, Sahoo S, Wilsbacher LD, Vaughan DE, Quaggin SE, Ghosh AK (2017). A novel acetyltransferase p300 inhibitor ameliorates hypertension-associated cardio-renal fibrosis. Epigenetics, 12:1004-13.
[23] Rai R, Sun T, Ramirez V, Lux E, Eren M, Vaughan DE, Ghosh AK (2019). Acetyltransferase p300 inhibitor reverses hypertension-induced cardiac fibrosis. J Cell Mol Med, 23:3026-31.
[24] Bugyei-Twum A, Advani A, Advani SL, Zhang Y, Thai K, Kelly DJ, Connelly KA (2014). High glucose induces Smad activation via the transcriptional coregulator p300 and contributes to cardiac fibrosis and hypertrophy. Cardiovasc Diabetol, 13:89.
[25] Kassimatis TI, Giannopoulou I, Koumoundourou D, Theodorakopoulou E, Varakis I, Nakopoulou L (2006). Immunohistochemical evaluation of phosphorylated SMAD2/SMAD3 and the co-activator p300 in human glomerulonephritis: correlation with renal injury. J Cell Mol Med, 10:908-21.
[26] Yao W, Wang T, Huang F (2018). p300/CBP as a key nutritional sensor for hepatic energy homeostasis and liver fibrosis. Biomed Res Int, 2018: 8168791.
[27] Kemper JK, Xiao Z, Ponugoti B, Miao J, Fang S, Kanamaluru D, Tsang S, Wu SY, Chiang CM, Veenstra TD (2009). FXR acetylation is normally dynamically regulated by p300 and SIRT1 but constitutively elevated in metabolic disease states. Cell Metab, 10:392-404.
[28] Zhang E, Guo Q, Gao H, Xu R, Teng S, Wu Y (2015). Metformin and Resveratrol Inhibited High Glucose-Induced Metabolic Memory of Endothelial Senescence through SIRT1/p300/p53/p21 Pathway. PLoS One, 10:e0143814.
[29] Tezil T, Chamoli M, Ng CP, et al (2019). Lifespan-increasing drug nordihydroguaiaretic acid inhibits p300 and activates autophagy. NPJ Aging Mech Dis, 5:7.
[30] Oliveira AM, Estévez MA, Hawk JD, Grimes S, Brindle PK, Abel T (2011). Subregion-specific p300 conditional knock-out mice exhibit long-term memory impairments. Learn Mem, 18:161-69.
[31] Kasper LH, Boussouar F, Ney PA, Jackson CW, Rehg J, van Deursen JM, Brindle PK (2002). A transcription-factor-binding surface of coactivator p300 is required for haematopoiesis. Nature, 419:738-43.
[32] Shikama N, Lutz W, Kretzschmar R, et al (2003). Essential function of p300 acetyltransferase activity in heart, lung and small intestine formation. EMBO J. 2003; 22:5175-5185.
[33] Kumar R, Mahapatra SS, Datta M, Hoque A, Datta S, Ghosh S, Datta S, Bhattacharjee S (2014). Holt-oram syndrome in adult presenting with heart failure: a rare presentation. Case Rep Cardiol, 2014:130617.
[34] Murakami M, Nakagawa M, Olson EN, Nakagawa O (2005). A WW domain protein TAZ is a critical coactivator for TBX5, a transcription factor implicated in Holt-Oram syndrome. Proc Natl Acad Sci USA, 102:18034-39.
[35] Nakagawa Y, Kuwahara K, Takemura G, et al. (2009). p300 plays a critical role in maintaining cardiac mitochondrial function and cell survival in postnatal hearts. Circ Res, 105:746-54.
[36] Schier AF (2003). Nodal signaling in vertebrate development. Ann Rev Cell Dev Biol, 19:589-621.
[37] Su D, Li Q, Guan L, Gao X, Zhang H, Dandan E, Zhang L, Ma X (2013). Down-regulation of EBAF in the heart with ventricular septal defects and its regulation by histone acetyltransferase p300 and transcription factors smad2 and cited2. Biochim Biophys Acta, 1832:2145-52.
[38] Sun H, Zhu J, Lu T, Huang X, Tian J (2014). Curcumin-mediated cardiac defects in mouse is associated with a reduced histone H3 acetylation and reduced expression of cardiac transcription factors. Cardiovasc Toxicol, 14:162-9.
[39] Zhou W, Jiang D, Tian J, Liu L, Lu T, Huang X, Sun H (2018) Acetylation of H3K4, H3K9, and H3K27 mediated by p300 regulates the expression of GATA4 in cardiocytes. Genes Dis. 6:318-25.
[40] Poizat C, Sartorelli V, Chung G, Kloner RA, Kedes L (2000). Proteasome-mediated degradation of the coactivator p300 impairs cardiac transcription. Mol Cell Biol, 20:8643-54.
[41] Mathiyalagan P, Chang L, Du XJ, El-Osta A (2010). Cardiac ventricular chambers are epigenetically distinguishable. Cell Cycle, 9:612-17.
[42] Ghosh AK, Yuan W, Mori Y, Varga J (2000). Smad-dependent stimulation of type I collagen gene expression in human skin fibroblasts by TGF-beta involves functional cooperation with p300/CBP transcriptional coactivators. Oncogene, 19:3546-55.
[43] Ghosh AK, Yuan W, Mori Y, Chen Sj, Varga J (2001). Antagonistic regulation of type I collagen gene expression by interferon-gamma and transforming growth factor-beta. Integration at the level of p300/CBP transcriptional coactivators. J Biol Chem, 276:11041-48.
[44] Verrecchia F, Pessah M, Atfi A, Mauviel A (2000). Tumor necrosis factor-alpha inhibits transforming growth factor-beta/Smad signaling in human dermal fibroblasts via AP-1 activation. J Biol Chem, 275:30226-31.
[45] Czuwara-Ladykowska J, Sementchenko VI, Watson DK, Trojanowska M (2002). Ets1 is an effector of the transforming growth factor beta (TGF-beta) signaling pathway and an antagonist of the profibrotic effects of TGF-beta. J Biol Chem, 277:20399-408.
[46] Ghosh AK (2002). Factors involved in the regulation of type I collagen gene expression: implication in fibrosis. Exp Biol Med (Maywood), 227:301-14.
[47] Ghosh AK, Quaggin SE, Vaughan DE (2013). Molecular basis of organ fibrosis: potential therapeutic approaches. Exp Biol Med, 238:461-81.
[48] Ghosh AK, Bradham WS, Gleaves LA, et al. (2010). Genetic deficiency of plasminogen activator inhibitor-1 promotes cardiac fibrosis in aged mice: Involvement of constitutive TGF-β signaling and endothelial-to-mesenchymal transition. Circulation, 122:1200-209.
[49] Ghosh AK, Nagpal V, Covington JW, Michaels MA, Vaughan DE (2012). Molecular basis of cardiac endothelial-to-mesenchymal transition (EndMT): Differential expression of microRNAs during EndMT. Cellular Signal, 24:1031-36.
[50] Feng B, Cao Y, Chen S, Chu X, Chu Y, Chakrabarti S (2016). miR-200b Mediates Endothelial-to-Mesenchymal Transition in Diabetic Cardiomyopathy. Diabetes, 65:768-79.
[51] Frey N, Katus HA, Olson EN, Hill JA (2004). Hypertrophy of the heart: a new therapeutic target? Circulation, 109:1580-89.
[52] Gusterson RJ, Jazrawi E, Adcock IM, Latchman DS (2003). The transcriptional co-activators CREB-binding protein (CBP) and p300 play a critical role in cardiac hypertrophy that is dependent on their histone acetyltransferase activity. J Biol Chem, 278:6838-47.
[53] Yanazume T, Hasegawa K, Morimoto T, et al (2003). Cardiac p300 is involved in myocyte growth with decompensated heart failure. Mol Cell Biol, 233:593-606.
[54] Takaya T, Kawamura T, Morimoto T, Ono K, Kita T, Shimatsu A, Hasegawa K (2008). Identification of p300-targeted acetylated residues in GATA4 during hypertrophic responses in cardiac myocytes. J Biol Chem, 283:9828-35.
[55] Shen P, Feng X, Zhang X, et al. (2016). SIRT6 suppresses phenylephrine-induced cardiomyocyte hypertrophy though inhibiting p300. J Pharmacol Sci, 132: 31-40.
[56] Peng C, Zhang W, Zhao W, Zhu J, Huang X, Tian J (2015). Alcohol-induced histone H3K9 hyperacetylation and cardiac hypertrophy are reversed by a histone acetylases inhibitor anacardic acid in developing murine hearts. Biochimie, 113:1-9.
[57] Wu X, Pan B, Liu L, Zhao W, Zhu J, Huang X, Tian J (2019). In utero exposure to PM2.5 during gestation caused adult cardiac hypertrophy through histone acetylation modification. J Cell Biochem, 120:4375-84.
[58] Peng C, Luo X, Li S, Sun H (2017). Phenylephrine-induced cardiac hypertrophy is attenuated by a histone acetylase inhibitor anacardic acid in mice. Mol Biosyst, 13:714-24.
[59] Sunagawa Y, Morimoto T, Wada H, Takaya T, et al (2011). A natural p300-specific histone acetyltransferase inhibitor, curcumin, in addition to angiotensin-converting enzyme inhibitor, exerts beneficial effects on left ventricular systolic function after myocardial infarction in rats. Circ J, 75:2151-59.
[60] Miyamoto S, Kawamura T, Morimoto T, et al. (2006). Histone acetyltransferase activity of p300 is required for the promotion of left ventricular remodeling after myocardial infarction in adult mice in vivo. Circulation, 113:679-90.
[61] Morimoto T, Sunagawa Y, Kawamura T, et al. (2008). The dietary compound curcumin inhibits p300 histone acetyltransferase activity and prevents heart failure in rats. J Clin Invest, 118:868-78.
[62] Paulraj F, Abas F, H Lajis N, Othman I, Naidu R (2019). Molecular Pathways Modulated by Curcumin Analogue, Diarylpentanoids in Cancer. Biomolecules, 9. pii: E270.
[63] Haldar SM, Lu Y, Jeyaraj D, et al. (2010). Klf15 deficiency is a molecular link between heart failure and aortic aneurysm formation. Sci Transl Med, 2: 26ra26.
[64] Kuno A, Hori YS, Hosoda R, Tanno M, Miura T, Shimamoto K, Horio Y (2013). Resveratrol improves cardiomyopathy in dystrophin-deficient mice through SIRT1 protein-mediated modulation of p300 protein. J Biol Chem, 288:5963-72.
[65] Kuno A, Tanno M, Horio Y (2015). The effects of resveratrol and SIRT1 activation on dystrophic cardiomyopathy. Ann N Y Acad Sci, 1348:46-54.
[66] Feng B, Chen S, Chiu J, George B, Chakrabarti S (2008). Regulation of cardiomyocyte hypertrophy in diabetes at the transcriptional level. Am J Physiol Endocrinol Metab, 294:E1119-E1126.
[67] Lee IH, Finkel T (2009). Regulation of autophagy by the p300 acetyltransferase?. . Biol. Chem. 284, 6322-28.
[68] Henry RA, Kuo Y-M, Siegel Z-S, et al. (2019). Discordant Effects of Putative Lysine Acetyltransferase Inhibitors in Biochemical and Living Systems. Cells, 8:1022.
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