Platelet Rich Plasma (PRP) Treatment: A Viable Treatment for Myocardial Ischemic Reperfusion Injury
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Abstract
Myocardial infarction and several surgical and vascular procedures contribute to MIRI. Research has primarily focused on the restoration of blood flow to the ischemic tissue. However, an inherent response to restoring blood flow to heart tissue after ischemia is reperfusion injury generated in part by an increase in the production of reactive oxygen species (ROS). Platelet-rich plasma (PRP) is a promising treatment for supporting cardiomyocytes exposed to MIRI and oxidative stress. We assessed the effects of PRP in the presence or absence of the NOX- 2 or NOX-4 inhibitors using the rabbit Langendorf heart method of MIRI and in cardiac myoblast cells (H9c2) and Adipose Derived Stem Cells (ADSC) exposed to hypoxia. Left ventricular systolic (LVSP), diastolic (LVDP), and work function (LVWF) were analyzed in the Langendorff hearts. The ROS concentration, hypoxia-inducible factor 1-alpha activity, and channel formation were analyzed in cardiac myoblast cells, in vitro.
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Eltzschig HK, Eckle T. Ischemia and reperfusion—from mechanism to translation. Nat Med. 2011;17:1391-1401. Available from: https://doi.org/10.1038/nm.2507
Ebrahimi S, Esfahani SA, Kohkiloezadeh M, Moghaddam BH, Askarian S, Tanideh N, Tamadon A. A model of cerebral ischemia induction in neonatal rabbits. JAAR. 2021;40:37-42.
Piper HM, Meuter K, Schafer C. Cellular mechanisms of ischemia-reperfusion injury. Ann Thorac Surg. 2003;75:S644-S648. Available from: https://doi.org/10.1016/s0003-4975(02)04686-6
Tavakoli F, Ostad SN, Khori V, Alizadeh AM, Sadeghpour A, Azar AD, et al. Outcome improvement of cellular cardiomyoplasty using triple therapy: mesenchymal stem cell, erythropoietin, and vascular endothelial growth factor. Eur J Pharmacol. 2013;714:456-463. Available from: https://doi.org/10.1016/j.ejphar.2013.07.001
Pagliaro BR, Cannata F, Stefanini GG. Myocardial ischemia and coronary disease in heart failure. Heart Fail Rev. 2020;25:53-65. Available from: https://doi.org/10.1007/s10741-019-09831-z
Tognoloni A, Bartolini D, Pepe M, Meo A, Parcellato I, Guidoni K, et al. Platelet-rich plasma increases antioxidant defenses of tenocytes via the Nrf2 signalling pathway. Int J Mol Sci. 2023;24(17):13299. Available from: https://doi.org/10.3390/ijms241713299
Hargrave BY. Autologous platelet-rich plasma (platelet gel): an appropriate intervention for salvaging cardiac myocytes under oxidative stress after myocardial infarction. Anat Physiol. 2014;4(1):1-8. Available from: https://digitalcommons.odu.edu/cgi/viewcontent.cgi?article=1129&context=bioelectrics_pubs
Hargrave B, Li F. Nanosecond pulse electric field activation of platelet-rich plasma reduces myocardial infarct size and improves left ventricular mechanical function in the rabbit heart. J Extra Corpor Technol. 2012;44(4):198-204. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC4557561/
Matsushima S, Tsutsui H, Sadoshima J. Physiological and pathological functions of NADPH oxidases during myocardial ischemia-reperfusion. Trends Cardiovasc Med. 2014;24(5):202-205. Available from: https://doi.org/10.1016/j.tcm.2014.03.003
Tang XL, Takano H, Rizvi A, Turrens JF, Qiu Y, Wu WJ, et al. Oxidant species trigger late preconditioning against myocardial stunning in conscious rabbits. Am J Physiol Heart Circ Physiol. 2002;282(1):H281-H291. Available from: https://doi.org/10.1152/ajpheart.2002.282.1.h281
Hargrave B, Varghese F, Barabutis N, Catravas J, Zemlin C. Nanosecond pulsed platelet-rich plasma (nsPRP) improves mechanical and electrical cardiac function following myocardial reperfusion injury. Physiol Rep. 2016;4(4):e12710. Available from: https://doi.org/10.14814/phy2.12710
Mosser DD, Caron AW, Bourget L, Meriin AB, Sherman MY, Morimoto RI, et al. The chaperone function of Hsp70 is required for protection against stress-induced apoptosis. Mol Cell Biol. 2000;20(19):7146-7159. Available from: https://doi.org/10.1128/mcb.20.19.7146-7159.2000
Kayama T, Nakazawa T, Thanos A, Morizane Y, Murakami Y, Theodoropoulou S, et al. Heat shock protein 70 (HSP70) is critical for the photoreceptor stress response after retinal detachment via modulating anti-apoptotic Akt kinase. Am J Pathol. 2011;178(3):1080-1091. Available from: https://doi.org/10.1016/j.ajpath.2010.11.072
Ziello JE, Jovin IS, Huang Y. Hypoxia-inducible factor (HIF)-1 regulatory pathway and its potential for therapeutic intervention in malignancy and ischemia. Yale J Biol Med. 2007;80(2):51-60. Available from: https://pubmed.ncbi.nlm.nih.gov/18160990/
Genbacev O, Zhou Y, Ludlow JW, Fisher SJ. Regulation of human placental development by oxygen tension. Science. 1997;277(5332):1669-1672. Available from: https://doi.org/10.1126/science.277.5332.1669
Matsushima S, Sadoshima J. Yin and yang of NADPH oxidases in myocardial ischemia-reperfusion. Antioxidants (Basel). 2022;11(6):1069. Available from: https://doi.org/10.3390/antiox11061069
Endemann DH, Schiffrin EL. Endothelial dysfunction. J Am Soc Nephrol. 2004;15(8):1983-1992. Available from: https://doi.org/10.1097/01.asn.0000132474.50966.da
Burgoyne JR, Madhani M, Cuello F, Charles RL, Brennan JP, Schröder E, et al. Cysteine redox sensor in PKGIalpha enables oxidant-induced activation. Science. 2007;317(5843):1393-1397. Available from: https://doi.org/10.1126/science.1144318
Kleinschnitz C, Grund H, Wingler K, Armitage ME, Jones E, Mittal M, et al. Post-stroke inhibition of induced NADPH oxidase type 4 prevents oxidative stress and neurodegeneration. PLoS Biol. 2010;8(9):e1000479. Available from: https://doi.org/10.1371/journal.pbio.1000479
Braunersreuther V, Montecucco F, Asrih M, Pelli G, Galan K, Frias M, et al. Role of NADPH oxidase isoforms NOX1, NOX2, and NOX4 in myocardial ischemia/reperfusion injury. J Mol Cell Cardiol. 2013;64:99-107. Available from: https://doi.org/10.1016/j.yjmcc.2013.09.007
Matsushima S, Kuroda J, Ago T, Zhai P, Ikeda Y, Oka S, et al. Broad suppression of NADPH oxidase activity exacerbates ischemia/reperfusion injury through inadvertent downregulation of hypoxia-inducible factor-1alpha and upregulation of peroxisome proliferator-activated receptor-alpha. Circ Res. 2013;112(8):1135-1149. Available from: https://doi.org/10.1161/circresaha.111.300171
Siu KL, Lotz C, Ping P, Cai H. Netrin-1 abrogates ischemia/reperfusion-induced cardiac mitochondrial dysfunction via nitric oxide-dependent attenuation of NOX4 activation and recoupling of NOS. J Mol Cell Cardiol. 2015;78:174-185. Available from: https://doi.org/10.1016/j.yjmcc.2014.07.005
Schröder K, Zhang M, Benkhoff S, Mieth A, Pliquett R, Kosowski J, et al. Nox4 is a protective reactive oxygen species-generating vascular NADPH oxidase. Circ Res. 2012;110(9):1217-1225. Available from: https://doi.org/10.1161/circresaha.112.267054
Ago T, Kuroda J, Pain J, Fu C, Li H, Sadoshima J. Upregulation of Nox4 by hypertrophic stimuli promotes apoptosis and mitochondrial dysfunction in cardiac myocytes. Circ Res. 2010;106(7):1253-1264. Available from: https://doi.org/10.1161/circresaha.109.213116
Kloner RA, King KS, Harrington MG. No-reflow phenomenon in the heart and brain. Am J Physiol Heart Circ Physiol. 2018;315(3):H550-H562. Available from: https://doi.org/10.1152/ajpheart.00183.2018
Smyth JW, Hong TT, Gao D, Vogan JM, Jensen BC, Fong TS, et al. Limited forward trafficking of connexin 43 reduces cell-cell coupling in stressed human and mouse myocardium. J Clin Invest. 2010;120(1):266-279. Available from: https://doi.org/10.1172/jci39740
Smyth JW, Shaw RM. The gap junction life cycle. Heart Rhythm. 2012;9(1):151-153. Available from: https://doi.org/10.1016/j.hrthm.2011.07.028
Kaur G, Baghdasaryan P, Natarajan B, Sethi P, Mukherjee A, Varadarajan P, et al. Pathophysiology, diagnosis, and management of coronary no-reflow phenomenon. Int J Angiol. 2022;31:107-112. Available from: https://doi.org/10.1055/s-0041-1725979
Dil S, Ryabov V, Maslov L, Mochula O, Mochula A, Kercheva M, et al. Assessing coronary microvascular dysfunction in refractory no-reflow: insights from dynamic myocardial perfusion scintigraphy and cardiac MRI. Microvasc Res. 2025;162:104862. Available from: https://doi.org/10.1016/j.mvr.2025.104862
Gallo I, Sáenz A, Arévalo A, Roussel S, Pérez-Moreiras I, Artiñano E, et al. Effect of autologous platelet-rich plasma on heart infarction in sheep. Arch Cardiol Mex. 2013;83:154-158. Available from: https://doi.org/10.1016/j.acmx.2013.04.011
Mishra A, Velotta J, Brinton TJ, Wang X, Chang S, Palmer O, et al. RevaTen platelet-rich plasma improves cardiac function after myocardial injury. Cardiovasc Revasc Med. 2011;12:158-163. Available from: https://doi.org/10.1016/j.carrev.2010.08.005
Vu TD, Pal SN, Ti LK, Martinez EC, Rufaihah AJ, Ling LH, et al. An autologous platelet-rich plasma hydrogel compound restores left ventricular structure, function and ameliorates adverse remodeling in a minimally invasive large animal myocardial restoration model: a translational approach. Biomaterials. 2015;45:27-35. Available from: https://doi.org/10.1016/j.biomaterials.2014.12.013
Yu FX, Zhang Y, Tran N, Fu Y, Liao B, Shi YK. Effects of myocardial platelet-rich plasma injection on rats with acute myocardial infarction: 99Tc(m)-MIBI gated SPECT imaging evaluation results. Zhonghua Xinxue Guanbing Zazhi. 2012;40:392-396. Available from: https://scispace.com/papers/effects-of-myocardial-platelet-rich-plasma-injection-on-rats-2qcyk1opjx
Sun CK, Zhen YY, Leu S, Tsai TH, Chang LT, Sheu JJ, et al. Direct implantation versus platelet-rich fibrin-embedded adipose-derived mesenchymal stem cells in treating rat acute myocardial infarction. Int J Cardiol. 2014;173:410-423. Available from: https://doi.org/10.1016/j.ijcard.2014.03.015
Sirker A, Zhang M, Murdoch C, Shah AM. Involvement of NADPH oxidases in cardiac remodelling and heart failure. Am J Nephrol. 2007;27(6):649-660. Available from: https://doi.org/10.1159/000109148
Ago T, Matsushima S, Kuroda J, Zablocki D, Kitazono T, Sadoshima J. The NADPH oxidase Nox4 and aging in the heart. Aging (Albany NY). 2010;2(12):1012-1016. Available from: https://doi.org/10.18632/aging.100261
Chi S. The role of Piezo1 channels in cardiovascular function: mechanotransduction in the heart and blood vessels. Series Cardiol Res. 2025;7(1):1-4. Available from: https://seriesscience.com/wp-content/uploads/2025/03/Piezo1-Channels-in-CV-Function.pdf
Coste B, Mathur J, Schmidt M, Earley TJ, Ranade S, Petrus MJ, et al. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science. 2010;330(6000):55-60. Available from: https://doi.org/10.1126/science.1193270
McGrane A, Murray M, Bartoli F, Giannoudi M, Conning-Rowland M, Stewart L, et al. PIEZO force sensors and the heart. Cold Spring Harb Perspect Biol. 2026;18(2):a041806. Available from: https://doi.org/10.1101/cshperspect.a041806
Novosolova N, Braidotti N, Patinen T, Laitinen T, Ciubotaru C, Huttunen KM, et al. Oxidative modulation of Piezo1 channels. Redox Biol. 2025;86:103797. Available from: https://doi.org/10.1016/j.redox.2025.103797