Abstract
Defective vascular and cardiomyocyte function are implicated in the development and progression of both heart failure with reduced and preserved ejection fraction. Any treatment option that augments these myocardial processes may therefore be of significant value. The platelet-derived growth factor (PDGF) family is involved in a wide range of growth processes and plays a key role in both regulating angiogenesis and mesenchymal cell development. Thus, PDGF may serve as a potent therapy for heart failure. While numerous animal studies have demonstrated beneficial cardiovascular effects of growth factor therapy, promising laboratory data has not yet translated to effective therapies. In this review, we outline the biological role of PDGF and summarize previous studies that have focused on the cardiovascular effects of normal PDGF signaling, administration of PDGF, and the effects of PDGF on stem cell therapy.
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Abbreviations
- Ang-2:
-
Angiopoietin-2
- CK-MB:
-
Creatine phosphokinase-myocardial band
- FGF:
-
Basic fibroblast growth factor
- HF:
-
Heart failure
- HFpEF:
-
Heart failure with preserved ejection fraction
- HSP:
-
Heat shock protein
- IGF-1:
-
Insulin-like growth factor
- LDH:
-
Lactate dehydrogenase
- MAP:
-
Mitogen-activated protein
- MEK:
-
Mitogen-activated ERK-activating kinase
- PDGF:
-
Platelet-derived growth factor
- PKC:
-
Protein kinase C
- PLC:
-
Phospholipase C
- VEGF:
-
Vascular endothelial growth factor
References
Affleck DG, Bull DA, Bailey SH, Albanil A, Connors R, Stringham JC, Karwande SV (2002) PDGF(BB) increases myocardial production of VEGF: shift in VEGF mRNA splice variants after direct injection of bFGF, PDGF(BB), and PDGF(AB). J Surg Res 107:203–209
Annex BH, Simons M (2005) Growth factor-induced therapeutic angiogenesis in the heart: protein therapy. Cardiovasc Res 65:649–655
Awada HK, Johnson NR, Wang Y (2015) Sequential delivery of angiogenic growth factors improves revascularization and heart function after myocardial infarction. J Control Release 207:7–17
Backs J, Olson EN (2006) Control of cardiac growth by histone acetylation/deacetylation. Circ Res 98:15–24
Betsholtz C (2004) Insight into the physiological functions of PDGF through genetic studies in mice. Cytokine Growth Factor Rev 15:215–228
Cheng M, Park H, Engelmayr GC, Moretti M, Freed LE (2007) Effects of regulatory factors on engineered cardiac tissue in vitro. Tissue Eng 13:2709–2719
Chong JJ, Reinecke H, Iwata M, Torok-Storb B, Stempien-Otero A, Murry CE (2013) Progenitor cells identified by PDGFR-alpha expression in the developing and diseased human heart. Stem Cells Dev 22:1932–1943
Cui K, Zhou X, Luo J, Feng J, Zheng M, Huang D, Jiang J, Chen X, Wei Y, Li J, Yang L (2014) Dual gene transfer of bFGF and PDGF in a single plasmid for the treatment of myocardial infarction. Exp Ther Med 7:691–696
Das H, George JC, Joseph M, Das M, Abdulhameed N, Blitz A, Khan M, Sakthivel R, Mao H-Q, Hoit BD, Kuppusamy P, Pompili VJ (2009) Stem cell therapy with overexpressed VEGF and PDGF genes improves cardiac function in a rat infarct model. PLoS One 4:e7325
de Maio A (1999) Heat shock proteins: facts, thoughts, and dreams. Shock 11:1–12
Edelberg JM, Aird WC, Wu W, Rayburn H, Mamuya WS, Mercola M, Rosenberg RD (1998) PDGF mediates cardiac microvascular communication. J Clin Invest 102:837–843
Edelberg JM, Lee SH, Kaur M, Tang L, Feirt NM, McCabe S, Bramwell O, Wong SC, Hong MK (2002) Platelet-derived growth factor-AB limits the extent of myocardial infarction in a rat model: feasibility of restoring impaired angiogenic capacity in the aging heart. Circulation 105:608–613
Formiga FR, Tamayo E, Simon-Yarza T, Pelacho B, Prosper F, Blanco-Prieto MJ (2012) Angiogenic therapy for cardiac repair based on protein delivery systems. Heart Fail Rev 17:449–473
Fredriksson L, Li H, Eriksson U (2004) The PDGF family: four gene products form five dimeric isoforms. Cytokine Growth Factor Rev 15:197–204
Genneback N, Hellman U, Malm L, Larsson G, Ronquist G, Waldenstrom A, Morner S (2013) Growth factor stimulation of cardiomyocytes induces changes in the transcriptional contents of secreted exosomes. J Extracell Vesicles 2
Gladden JD, Linke WA, Redfield MM (2014) Heart failure with preserved ejection fraction. Eur J Physiol 466:1037–1053
Hao X, Mansson-Broberg A, Gustafsson T, Grinnemo KH, Blomberg P, Siddiqui AJ, Wardell E, Sylven C (2004) Angiogenic effects of dual gene transfer of bFGF and PDGF-BB after myocardial infarction. Biochem Biophys Res Commun 315:1058–1063
Hao X, Silva EA, Mansson-Broberg A, Grinnemo KH, Siddiqui AJ, Dellgren G, Wardell E, Brodin LA, Mooney DJ, Sylven C (2007) Angiogenic effects of sequential release of VEGF-A165 and PDGF-BB with alginate hydrogels after myocardial infarction. Cardiovasc Res 75:178–185
Heldin CH, Westermark B (1999) Mechanism of action and in vivo role of platelet-derived growth factor. Physiol Rev 79:1283–1316
Hellman U, Malm L, Ma L-P, Larsson G, Mörner S, Fu M, Engström-Laurent A, Waldenström A (2010) Growth factor PDGF-BB stimulates cultured cardiomyocytes to synthesize the extracellular matrix component hyaluronan. PLoS One 5:e14393
Hoch RV, Soriano P (2003) Roles of PDGF in animal development. Development 130:4769–4784
Hsieh PCH, Davis ME, Gannon J, MacGillivray C, Lee RT (2006a) Controlled delivery of PDGF-BB for myocardial protection using injectable self-assembling peptide nanofibers. J Clin Invest 116:237–248
Hsieh PC, MacGillivray C, Gannon J, Cruz FU, Lee RT (2006b) Local controlled intramyocardial delivery of platelet-derived growth factor improves postinfarction ventricular function without pulmonary toxicity. Circulation 114:637–644
Jemal A, Ward E, Hao Y, Thun M (2005) Trends in the leading causes of death in the United States, 1970-2002. JAMA 294:1255–1259
Khattab RAM, Khorshied MMA, Abdel Shafy SS, El Ansary MS, Moukhtar MS (2013) In vitro transdifferentiation of umbilical cord stem cells into cardiac myocytes: Role of growth factors. Egypt J Crit Care Med 1:43–50
Kim JH, Jung Y, Kim SH, Sun K, Choi J, Kim HC, Park Y, Kim SH (2011) The enhancement of mature vessel formation and cardiac function in infarcted hearts using dual growth factor delivery with self-assembling peptides. Biomaterials 32:6080–6088
Koch A, Schmidt CI, Dengler TJ, Remppis A, Sack FU, Schirmacher P, Hagl S, Karck M, Schnabel PA (2007) Differentiated expression patterns of growth factors in routine formalin-fixed endomyocardial biopsies in the early postoperative phase after heart transplantation. Transplant Proc 39:554–557
Koizumi T, Kaneda H, Yamasaki T, Tamaki T, Kikutani T, Muramatsu T, Sano K, Komiyama N, Nishimura S (2015) Impact of platelet-derived growth factor-BB on ischemic myocardial injury after thrombus aspiration for ST-segment elevation myocardial infarction. Int J Cardiol 182:109–111
Krausgrill B, Vantler M, Burst V, Raths M, Halbach M, Frank K, Schynkowski S, Schenk K, Hescheler J, Rosenkranz S, Muller-Ehmsen J (2009) Influence of cell treatment with PDGF-BB and reperfusion on cardiac persistence of mononuclear and mesenchymal bone marrow cells after transplantation into acute myocardial infarction in rats. Cell Transplant 18:847–853
Lee RJ, Springer ML, Blanco-Bose WE, Shaw R, Ursell PC, Blau HM (2000) VEGF gene delivery to myocardium: deleterious effects of unregulated expression. Circulation 102:898–901
Lin F, Zhu J, Tonnesen MG, Taira BR, McClain SA, Singer AJ, Clark RAF (2014) Fibronectin peptides that bind PDGF-BB enhance survival of cells and tissue under stress. J Invest Dermatol 134:1119–1127
Liu J, Wu LL, Li L, Zhang L, Song ZE (2005) Growth-promoting effect of platelet-derived growth factor on rat cardiac myocytes. Regul Pept 127:11–18
Lu H, Xu X, Zhang M, Cao R, Bråkenhielm E, Li C, Lin H, Yao G, Sun H, Qi L, Tang M, Dai H, Zhang Y, Su R, Bi Y, Zhang Y, Cao Y (2007) Combinatorial protein therapy of angiogenic and arteriogenic factors remarkably improves collaterogenesis and cardiac function in pigs. Proc Natl Acad Sci 104:12140–12145
Miyata T, Iizasa H, Sai Y, Fujii J, Terasaki T, Nakashima E (2005) Platelet-derived growth factor-BB (PDGF-BB) induces differentiation of bone marrow endothelial progenitor cell-derived cell line TR-BME2 into mural cells, and changes the phenotype. J Cell Physiol 204:948–955
Mohammed SF, Hussain S, Mirzoyev SA, Edwards WD, Maleszewski JJ, Redfield MM (2015) Coronary microvascular rarefaction and myocardial fibrosis in heart failure with preserved ejection fraction. Circulation 131:550–559
Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M et al (2015) Heart disease and stroke statistics-2015 update: a report from the American Heart Association. Circulation 131:e29–e332
Price RD, Myers S, Leigh IM, Navsaria HA (2005) The role of hyaluronic acid in wound healing: assessment of clinical evidence. Am J Clin Dermatol 6:393–402
Rong R, Wang YC, Hu LQ, He QQ, Zhou XF, Wang TH, Bu PL (2015) Role of endogenous PDGF-BB in cultured cardiomyocytes exposed to hypoxia. Neuropeptides 50:43–49
Schweigerer L, Neufeld G, Friedman J, Abraham JA, Fiddes JC, Gospodarowicz D (1987) Capillary endothelial cells express basic fibroblast growth factor, a mitogen that promotes their own growth. Nature 325:257–259
Seok J, Warren HS, Cuenca AG, Mindrinos MN, Baker HV, Xu W, Richards DR, McDonald-Smith GP, Gao H, Hennessy L, Finnerty CC, López CM, Honari S, Moore EE, Minei JP, Cuschieri J, Bankey PE, Johnson JL, Sperry J, Nathens AB, Billiar TR, West MA, Jeschke MG, Klein MB, Gamelli RL, Gibran NS, Brownstein BH, Miller-Graziano C, Calvano SE, Mason PH, Cobb JP, Rahme LG, Lowry SF, Maier RV, Moldawer LL, Herndon DN, Davis RW, Xiao W, Tompkins RG (2013) Inflammation t and host response to injury LSCRP. Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci 110:3507–3512
Shaddy RE, Hammond EH, Yowell RL (1996) Immunohistochemical analysis of platelet-derived growth factor and basic fibroblast growth factor in cardiac biopsy and autopsy specimens of heart transplant patients. Am J Cardiol 77:1210–1215
Shantsila E, Lip GYH (2016) Endothelial progenitors and blood microparticles: are they relevant to heart failure with preserved ejection fraction? EBioMedicine 4:5–6
Sufen G, Xianghong Y, Yongxia C, Qian P (2011) bFGF and PDGF-BB have a synergistic effect on the proliferation, migration and VEGF release of endothelial progenitor cells. Cell Biol Int 35:545–551
Taimeh Z, Loughran J, Birks EJ, Bolli R (2013) Vascular endothelial growth factor in heart failure. Nat Rev Cardiol 10:519–530
Takahashi M, Li TS, Suzuki R, Kobayashi T, Ito H, Ikeda Y, Matsuzaki M, Hamano K (2006) Cytokines produced by bone marrow cells can contribute to functional improvement of the infarcted heart by protecting cardiomyocytes from ischemic injury. Am J Physiol Heart Circ Physiol 291:H886–H893
Takenaka M, Matsuno H, Ishisaki A, Nakajima K, Hirade K, Takei M, Yasuda E, Akamatsu S, Yoshimi N, Kato K, Kozawa O (2004) Platelet-derived growth factor-BB phosphorylates heat shock protein 27 in cardiac myocytes. J Cell Biochem 91:316–324
Tuuminen R, Dashkevich A, Keranen MA, Raissadati A, Krebs R, Jokinen JJ, Arnaudova R, Rouvinen E, Yla-Herttuala S, Nykanen AI, Lemstrom KB (2016) Platelet-derived growth factor-B protects rat cardiac allografts from ischemia-reperfusion injury. Transplantation 100:303–313
Vantler M, Karikkineth BC, Naito H, Tiburcy M, Didie M, Nose M, Rosenkranz S, Zimmermann WH (2010) PDGF-BB protects cardiomyocytes from apoptosis and improves contractile function of engineered heart tissue. J Mol Cell Cardiol 48:1316–1323
Xaymardan M, Tang L, Zagreda L, Pallante B, Zheng J, Chazen JL, Chin A, Duignan I, Nahirney P, Rafii S, Mikawa T, Edelberg JM (2004a) Platelet-derived growth factor-AB promotes the generation of adult bone marrow-derived cardiac myocytes. Circ Res 94:E39–E45
Xaymardan M, Zheng J, Duignan I, Chin A, Holm JM, Ballard VLT, Edelberg JM (2004b) Senescent impairment in synergistic cytokine pathways that provide rapid cardioprotection in the rat heart. J Exp Med 199:797–804
Zhao W, Zhao T, Huang V, Chen Y, Ahokas RA, Sun Y (2011) Platelet-derived growth factor involvement in myocardial remodeling following infarction. J Mol Cell Cardiol 51:830–838
Zheng J, Chin A, Duignan I, Won KH, Hong MK, Edelberg JM (2006) Growth factor-mediated reversal of senescent dysfunction of ischemia-induced cardioprotection. Am J Physiol Heart Circ Physiol 290:H525–H530
Zymek P, Bujak M, Chatila K, Cieslak A, Thakker G, Entman ML, Frangogiannis NG (2006) The role of platelet-derived growth factor signaling in healing myocardial infarcts. J Am Coll Cardiol 48:2315–2323
Acknowledgments
Funding for this manuscript was provided by a summer research grant from the Department of Dermatology at Stony Brook University Medical Center.
Conflict of Interest JM and JB report no conflict of interest. RC is the co-discoverer of a fibronectin-derived peptide that binds and enhances the activity of PDGF-BB and is the founder of NeoMatrix Therapeutics, which is developing the peptide to prevent burn injury progression, speed healing, and reduce scarring.
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Medamana, J., Clark, R.A., Butler, J. (2016). Platelet-Derived Growth Factor in Heart Failure. In: Bauersachs, J., Butler, J., Sandner, P. (eds) Heart Failure. Handbook of Experimental Pharmacology, vol 243. Springer, Cham. https://doi.org/10.1007/164_2016_80
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DOI: https://doi.org/10.1007/164_2016_80
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