A Narrative Review on the FSTL-1 Protein and its Current Known Impact in Cardiovascular Ischaemic Disease
Keywords:
Myocardial Ischemia, Coronary Artery Disease, FSTL-1, Follistatin-Related Proteins, Follistatin-Related Protein 1Abstract
Myocardial infarction (MI) is one of the leading causes of death worldwide, and even though modern medicine has reduced considerably the number of deaths due to MI, patients still undergo serious cardiac issues that dramatically affects their well-being. Since the start of the century, massive efforts have been employed in exploring stem cell therapy, however, it is believed that it has failed to live up to expectations and further work must done. Alongside this, FSTL-1 has been an emerging protein which seems to offer a multitude of benefits in post-MI. A considerable number of studies with FSTL-1 have been conducted, always with a very satisfactory level of success, especially considering that research is still in its preliminary phases. In this study, a general evaluation is done to 1) the known mechanisms regulated by FSTL-1, 2) the recognized effects of FSTL-1 in cardiac tissue and cells, 3) and what work can be done to clarify questions and further expand our knowledge in order to advance FSTL-1 as a potential therapeutic agent.
References
Rørholm Pedersen, L., Prescott, E., & Kerins, M. (n.d.). ESC prevention of CVD Programme: Epidemiology of IHD. ESC Prevention of CVD Programme: Epidemiology of IHD. Retrieved September 19, 2022, from https://www.escardio.org/Education/ESC-Prevention-of-CVD-Programme/Epidemiology-of-IHD
Urbanek K, Rota M, Cascapera S, Bearzi C, Nascimbene A, De Angelis A, Hosoda T, Chimenti S, Baker M, Limana F, Nurzynska D, Torella D, Rotatori F, Rastaldo R, Musso E, Quaini F, Leri A, Kajstura J, Anversa P. Cardiac stem cells possess growth factor-receptor systems that after activation regenerate the infarcted myocardium, improving ventricular function and long-term survival. Circ Res. 2005 Sep 30;97(7):663-73. doi: 10.1161/01.RES.0000183733.53101.11.
Bartunek J, Behfar A, Dolatabadi D, Vanderheyden M, Ostojic M, Dens J, El Nakadi B, Banovic M, Beleslin B, Vrolix M, Legrand V, Vrints C, Vanoverschelde JL, Crespo-Diaz R, Homsy C, Tendera M, Waldman S, Wijns W, Terzic A. Cardiopoietic stem cell therapy in heart failure: the C-CURE (Cardiopoietic stem Cell therapy in heart failURE) multicenter randomized trial with lineage-specified biologics. J Am Coll Cardiol. 2013 Jun 11;61(23):2329-38. doi: 10.1016/j.jacc.2013.02.071.
Emmert MY, Hitchcock RW, Hoerstrup SP. Cell therapy, 3D culture systems and tissue engineering for cardiac regeneration. Adv Drug Deliv Rev. 2014 Apr;69-70:254-69. doi: 10.1016/j.addr.2013.12.004
van der Spoel TI, Jansen of Lorkeers SJ, Agostoni P, van Belle E, Gyöngyösi M, Sluijter JP, Cramer MJ, Doevendans PA, Chamuleau SA. Human relevance of pre-clinical studies in stem cell therapy: systematic review and meta-analysis of large animal models of ischaemic heart disease. Cardiovasc Res. 2011 Sep 1;91(4):649-58. doi: 10.1093/cvr/cvr113.
Emmert, M.Y., 2017. Cell-based cardiac regeneration. European Heart Journal 38, 1095–1098.. doi:10.1093/eurheartj/ehx152
Ojha N, Dhamoon AS. Myocardial Infarction. 2020 Nov 21. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan–. PMID: 30725761.
Jugdutt BI. Ventricular remodeling after infarction and the extracellular collagen matrix: when is enough enough? Circulation. 2003 Sep 16;108(11):1395-403. doi: 10.1161/01.CIR.0000085658.98621.49.
Nahrendorf M, Swirski FK, Aikawa E, Stangenberg L, Wurdinger T, Figueiredo JL, Libby P, Weissleder R, Pittet MJ. The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J Exp Med. 2007 Nov 26;204(12):3037-47. doi: 10.1084/jem.20070885.
Santini MP, Tsao L, Monassier L, Theodoropoulos C, Carter J, Lara-Pezzi E, Slonimsky E, Salimova E, Delafontaine P, Song YH, Bergmann M, Freund C, Suzuki K, Rosenthal N. Enhancing repair of the mammalian heart. Circ Res. 2007 Jun 22;100(12):1732-40. doi: 10.1161/CIRCRESAHA.107.148791.
Pepper MS, Belin D, Montesano R, Orci L, Vassalli JD. Transforming growth factor-beta 1 modulates basic fibroblast growth factor-induced proteolytic and angiogenic properties of endothelial cells in vitro. J Cell Biol. 1990 Aug;111(2):743-55. doi: 10.1083/jcb.111.2.743.
Shiojima I, Walsh K. Regulation of cardiac growth and coronary angiogenesis by the Akt/PKB signaling pathway. Genes Dev. 2006 Dec 15;20(24):3347-65. doi: 10.1101/gad.1492806.
Ouchi N, Oshima Y, Ohashi K, Higuchi A, Ikegami C, Izumiya Y, Walsh K. Follistatin-like 1, a secreted muscle protein, promotes endothelial cell function and revascularization in ischemic tissue through a nitric-oxide synthase-dependent mechanism. J Biol Chem. 2008 Nov 21;283(47):32802-11. doi: 10.1074/jbc.M803440200.
Ogura Y, Ouchi N, Ohashi K, Shibata R, Kataoka Y, Kambara T, Kito T, Maruyama S, Yuasa D, Matsuo K, Enomoto T, Uemura Y, Miyabe M, Ishii M, Yamamoto T, Shimizu Y, Walsh K, Murohara T. Therapeutic impact of follistatin-like 1 on myocardial ischemic injury in preclinical models. Circulation. 2012 Oct 2;126(14):1728-38. doi: 10.1161/CIRCULATIONAHA.112.115089.
Beauloye C, Bertrand L, Horman S, Hue L. AMPK activation, a preventive therapeutic target in the transition from cardiac injury to heart failure. Cardiovasc Res. 2011 May 1;90(2):224-33. doi: 10.1093/cvr/cvr034.
Oshima, Y., Ouchi, N., Sato, K., Izumiya, Y., Pimentel, D.R., Walsh, K., 2008. Follistatin-Like 1 Is an Akt-Regulated Cardioprotective Factor That Is Secreted by the Heart. Circulation 117, 3099–3108.. doi:10.1161/circulationaha.108.767673
Xi, Y., Gong, D.-W., Tian, Z., 2016. FSTL1 as a Potential Mediator of Exercise-Induced Cardioprotection in Post-Myocardial Infarction Rats. Scientific Reports 6, 32424.. doi:10.1038/srep32424
Yue TL, Wang C, Gu JL, Ma XL, Kumar S, Lee JC, Feuerstein GZ, Thomas H, Maleeff B, Ohlstein EH. Inhibition of extracellular signal-regulated kinase enhances Ischemia/Reoxygenation-induced apoptosis in cultured cardiac myocytes and exaggerates reperfusion injury in isolated perfused heart. Circ Res. 2000 Mar 31;86(6):692-9. doi: 10.1161/01.
Bueno OF, De Windt LJ, Tymitz KM, Witt SA, Kimball TR, Klevitsky R, Hewett TE, Jones SP, Lefer DJ, Peng CF, Kitsis RN, Molkentin JD. The MEK1-ERK1/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice. EMBO J. 2000 Dec 1;19(23):6341-50. doi: 10.1093/emboj/19.23.6341.
Cai Z, Zhong H, Bosch-Marce M, Fox-Talbot K, Wang L, Wei C, Trush MA, Semenza GL. Complete loss of ischaemic preconditioning-induced cardioprotection in mice with partial deficiency of HIF-1 alpha. Cardiovasc Res. 2008 Feb 1;77(3):463-70. doi: 10.1093/cvr/cvm035.
Muraski JA, Rota M, Misao Y, Fransioli J, Cottage C, Gude N, Esposito G, Delucchi F, Arcarese M, Alvarez R, Siddiqi S, Emmanuel GN, Wu W, Fischer K, Martindale JJ, Glembotski CC, Leri A, Kajstura J, Magnuson N, Berns A, Beretta RM, Houser SR, Schaefer EM, Anversa P, Sussman MA. Pim-1 regulates cardiomyocyte survival downstream of Akt. Nat Med. 2007 Dec;13(12):1467-75. doi: 10.1038/nm1671.
Maruyama S, Nakamura K, Papanicolaou KN, Sano S, Shimizu I, Asaumi Y, van den Hoff MJ, Ouchi N, Recchia FA, Walsh K. Follistatin-like 1 promotes cardiac fibroblast activation and protects the heart from rupture. EMBO Mol Med. 2016 Aug 1;8(8):949-66. doi: 10.15252/emmm.201506151.
Sorescu GP, Song H, Tressel SL, Hwang J, Dikalov S, Smith DA, Boyd NL, Platt MO, Lassègue B, Griendling KK, Jo H. Bone morphogenic protein 4 produced in endothelial cells by oscillatory shear stress induces monocyte adhesion by stimulating reactive oxygen species production from a nox1-based NADPH oxidase. Circ Res. 2004 Oct 15;95(8):773-9. doi: 10.1161/01.RES.0000145728.22878.45.
Geng Y, Dong Y, Yu M, et al. Follistatin-like 1 (Fstl1) is a bone morphogenetic protein (BMP) 4 signaling antagonist in controlling mouse lung development. Proceedings of the National Academy of Sciences of the United States of America. 2011 Apr;108(17):7058-7063. DOI: 10.1073/pnas.1007293108.
Formigli L, Manneschi LI, Nediani C, Marcelli E, Fratini G, Orlandini SZ, Perna AM. Are macrophages involved in early myocardial reperfusion injury? Ann Thorac Surg. 2001 May;71(5):1596-602. doi: 10.1016/s0003-4975(01)02400-6.
Zuidema MY, Zhang C. Ischemia/reperfusion injury: The role of immune cells. World J Cardiol. 2010 Oct 26;2(10):325-32. doi: 10.4330/wjc.v2.i10.325.
Pachori AS, Custer L, Hansen D, Clapp S, Kemppa E, Klingensmith J. Bone morphogenetic protein 4 mediates myocardial ischemic injury through JNK-dependent signaling pathway. J Mol Cell Cardiol. 2010 Jun;48(6):1255-65. doi: 10.1016/j.yjmcc.2010.01.010.
Formigli L, Manneschi LI, Nediani C, Marcelli E, Fratini G, Orlandini SZ, Perna AM. Are macrophages involved in early myocardial reperfusion injury? Ann Thorac Surg. 2001 May;71(5):1596-602. doi: 10.1016/s0003-4975(01)02400-6.
Zuidema MY, Zhang C. Ischemia/reperfusion injury: The role of immune cells. World J Cardiol. 2010 Oct 26;2(10):325-32. doi: 10.4330/wjc.v2.i10.325.
Shen, H., Cui, G., Li, Y. et al. Follistatin-like 1 protects mesenchymal stem cells from hypoxic damage and enhances their therapeutic efficacy in a mouse myocardial infarction model. Stem Cell Res Ther 10, 17 (2019). https://doi.org/10.1186/s13287-018-1111-y
Van Wijk, B., Gunst, Q.D., Moorman, A.F.M., Van Den Hoff, M.J.B., 2012. Cardiac Regeneration from Activated Epicardium. PLOS ONE 7, e44692.. doi:10.1371/journal.pone.0044692
Shimano, M., Ouchi, N., Nakamura, K., Van Wijk, B., Ohashi, K., Asaumi, Y., Higuchi, A., Pimentel, D.R., Sam, F., Murohara, T., Van Den Hoff, M.J.B., Walsh, K., 2011. Cardiac myocyte follistatin-like 1 functions to attenuate hypertrophy following pressure overload. Proceedings of the National Academy of Sciences 108, E899–E906.. doi:10.1073/pnas.1108559108
Wei, K., Serpooshan, V., Hurtado, C., Diez-Cuñado, M., Zhao, M., Maruyama, S., Zhu, W., Fajardo, G., Noseda, M., Nakamura, K., Tian, X., Liu, Q., Wang, A., Matsuura, Y., Bushway, P., Cai, W., Savchenko, A., Mahmoudi, M., Schneider, M.D., Van Den Hoff, M.J.B., Butte, M.J., Yang, P.C., Walsh, K., Zhou, B., Bernstein, D., Mercola, M., Ruiz-Lozano, P., 2015. Epicardial FSTL1 reconstitution regenerates the adult mammalian heart. Nature 525, 479–485.. doi:10.1038/nature15372
Chen W, Xia J, Hu P, Zhou F, Chen Y, Wu J, Lei W, Shen Z. Follistatin-like 1 protects cardiomyoblasts from injury induced by sodium nitroprusside through modulating Akt and Smad1/5/9 signaling. Biochem Biophys Res Commun. 2016 Jan 15;469(3):418-23. doi: 10.1016/j.bbrc.2015.12.026.
Pérez-Pomares, J.M., De La Pompa, J.L., 2011. Signaling During Epicardium and Coronary Vessel Development. Circulation Research 109, 1429–1442.. doi:10.1161/circresaha.111.245589
Ellison GM, Vicinanza C, Smith AJ, Aquila I, Leone A, Waring CD, Henning BJ, Stirparo GG, Papait R, Scarfò M, Agosti V, Viglietto G, Condorelli G, Indolfi C, Ottolenghi S, Torella D, Nadal-Ginard B. Adult c-kit(pos) cardiac stem cells are necessary and sufficient for functional cardiac regeneration and repair. Cell. 2013 Aug 15;154(4):827-42. doi: 10.1016/j.cell.2013.07.039.
Hambrock, H.O. , Kaufmann, B., Muller, S., Hanisch, F.G., Nose, K., Paulsson, M., Maurer,P., and Hartmann, U. (2004) Structural characterization of TSC-36/Flik: analysis of two charge isoforms. J. Biol. Chem., 27911727–11735.
Rossdeutsch A, Smart N, Dubé KN, Turner M, Riley PR. Essential role for thymosin β4 in regulating vascular smooth muscle cell development and vessel wall stability. Circ Res. 2012 Aug 3;111(4):e89-102. doi: 10.1161/CIRCRESAHA.111.259846.
Maruyama S, Nakamura K, Papanicolaou KN, Sano S, Shimizu I, Asaumi Y, van den Hoff MJ, Ouchi N, Recchia FA, Walsh K. Follistatin-like 1 promotes cardiac fibroblast activation and protects the heart from rupture. EMBO Mol Med. 2016 Aug 1;8(8):949-66. doi: 10.15252/emmm.201506151.
Smart N, Bollini S, Dubé KN, Vieira JM, Zhou B, Davidson S, Yellon D, Riegler J, Price AN, Lythgoe MF, Pu WT, Riley PR. De novo cardiomyocytes from within the activated adult heart after injury. Nature. 2011 Jun 8;474(7353):640-4. doi: 10.1038/nature10188.
Shrivastava S, Srivastava D, Olson EN, DiMaio JM, Bock-Marquette I. Thymosin beta4 and cardiac repair. Ann N Y Acad Sci. 2010 Apr;1194:87-96. doi: 10.1111/j.1749-6632.2010.05468.x.
Zhou B, Ma Q, Rajagopal S, Wu SM, Domian I, Rivera-Feliciano J, Jiang D, von Gise A, Ikeda S, Chien KR, Pu WT. Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart. Nature. 2008 Jul 3;454(7200):109-13. doi: 10.1038/nature07060.
Cao J, Poss KD. The epicardium as a hub for heart regeneration. Nat Rev Cardiol. 2018 Oct;15(10):631-647. doi: 10.1038/s41569-018-0046-4. PMID: 29950578
Görgens SW, Raschke S, Holven KB, Jensen J, Eckardt K, Eckel J. Regulation of follistatin-like protein 1 expression and secretion in primary human skeletal muscle cells. Arch Physiol Biochem. 2013 May;119(2):75-80. doi: 10.3109/13813455.2013.768270.
Miyabe, M., Ohashi, K., Shibata, R., Uemura, Y., Ogura, Y., Yuasa, D., Kambara, T., Kataoka, Y., Yamamoto, T., Matsuo, K., Joki, Y., Enomoto, T., Hayakawa, S., Hiramatsu-Ito, M., Ito, M., Van Den Hoff, M.J.B., Walsh, K., Murohara, T., Ouchi, N., 2014. Muscle-derived follistatin-like 1 functions to reduce neointimal formation after vascular injury. Cardiovascular Research 103, 111–120.. doi:10.1093/cvr/cvu105
Xi, Y., Gong, D.-W., Tian, Z., 2016. FSTL1 as a Potential Mediator of Exercise-Induced Cardioprotection in Post-Myocardial Infarction Rats. Scientific Reports 6, 32424.. doi:10.1038/srep32424
Kambara, T., Ohashi, K., Shibata, R., Ogura, Y., Maruyama, S., Enomoto, T., Uemura, Y., Shimizu, Y., Yuasa, D., Matsuo, K., Miyabe, M., Kataoka, Y., Murohara, T., Ouchi, N., 2012. CTRP9 Protein Protects against Myocardial Injury following Ischemia-Reperfusion through AMP-activated Protein Kinase (AMPK)-dependent Mechanism. Journal of Biological Chemistry 287, 18965–18973.. doi:10.1074/jbc.m112.357939
Miao, C., Lei, M., Hu, W., Han, S., Wang, Q., 2017. A brief review: the therapeutic potential of bone marrow mesenchymal stem cells in myocardial infarction. Stem Cell Research & Therapy 8.. doi:10.1186/s13287-017-0697-9
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