anatomyЖурнал анатомии и гистопатологииJournal of Anatomy and Histopathology2225-7357N.N. Burdenko Voronezh State Medical University10.18499/2225-7357-2024-13-2-24-31anatomy-1936Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL PAPERSИммуногистохимический анализ экспрессии матриксной металлопротеиназы-9 и тканевого ингибитора матриксных металлопротеиназ-1 в миокарде крыс в раннем постнатальном периоде при моделировании преждевременного рожденияImmunohistochemical analysis of matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1 expression in the myocardium of rats in the early postnatal period on preterm birth modelinghttps://orcid.org/0000-0002-2530-1112ИвановаВ. В.IvanovaV. V.

Иванова Вера Владимировна – канд. биол. наук, доцент кафедры морфологии и общей патологии

Московский тракт, 2, Томск, 634050

Vera V. Ivanova – Cand. Sci. (Biol.), Associate Professor of the Department of Morphology and General Pathology

Moskovskii trakt, 2, Tomsk, 634050

ivvera92@rambler.ruhttps://orcid.org/0000-0002-2924-0724СеребряковаО. Н.SerebryakovaO. N.

Серебрякова Ольга Николаевна – ассистент кафедры морфологии и общей патологии

Томск

Ol’ga N. Serebryakova – Postgraduate student of the Department of Morphology and General Pathology 

Tomsk

oserebryakovan@gmail.comhttps://orcid.org/0000-0002-9764-4392МильтоИ. В.MiltoI. V.

Мильто Иван Васильевич – д-р биол. наук, профессор, зав. кафедрой морфологии и общей патологии

Томск

Северск

Ivan V. Milto – Doct. Sci. (Biol.), Professor, head of the Department of Morphology and General Pathology

Tomsk

Seversk

Сибирский государственный медицинский университетРоссияSiberian State Medical UniversityRussian FederationСибирский государственный медицинский университет; Северский биофизический научный центрРоссияSiberian State Medical University; Seversk Biophysical Research CentreRussian Federation2024040720241322431Copyright © Иванова В.В., Серебрякова О.Н., Мильто И.В., 20242024Иванова В.В., Серебрякова О.Н., Мильто И.В.Ivanova V.V., Serebryakova O.N., Milto I.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://anatomy.elpub.ru/jour/article/view/1936

Преждевременное рождение сокращает продолжительность пренатального периода развития организма и нарушает закономерный морфогенез органов плода. Изучение тканевых и клеточных реакций в миокарде преждевременно рожденных детей невозможно из-за инвазивности процедуры, поэтому востребованными являются экспериментальные исследования. Цель исследования – провести иммуногистохимический анализ матриксной металлопротеиназы-9 (ММП-9) и тканевого ингибитора матриксной металлопротеиназы-1 (ТИМП-1) в миокарде левого желудочка преждевременно рожденных крыс с 1-х по 14-е сут постнатального периода. Материал и методы. Объектами исследования были сердца доношенных (n=15) и преждевременно рожденных (n=15) крыс-самцов Вистар. Сердца фиксировали в забуференном (рН 7,4) 10% растворе формалина. Материал заключали в парафин. Иммуногистохимическим непрямым пероксидазным методом с помощью антител на срезах выявляли ММП-9 и ТИМП-1. Интенсивность иммуногистохимической реакции оценивали полуколичественно (в баллах). Полученные данные обрабатывались методами непараметрической статистики. Результаты. Не обнаружено различий в локализации ММП-9- и ТИМП-1-позитивного окрашивания в миокарде преждевременно рожденных и доношенных животных. У преждевременно рожденных крыс на 7-е сут постнатального периода интенсивность окрашивания как на ММП-9, так и на ТИМП-1 снижена. На 14-е сут постнатального периода в миокарде у преждевременно рожденных крыс наблюдается повышение интенсивности иммуногистохимической реакции на ММП-9 на фоне реакции на ТИМП-1 низкой интенсивности. Заключение. Результаты исследования указывают на возможное усиление эффектов ММП-9 в миокарде преждевременно рожденных животных на 14-е сут постнатального периода. Дисбаланс ММП-9 и ТИМП-1 может вносить вклад в ремоделирование миокарда левого желудочка у преждевременно рожденных животных.

Preterm birth shortens the duration of the prenatal period of development of the fetus and disrupts the natural morphogenesis of fetal organs. The study of tissue and cellular reactions in the myocardium of preterm born children is impossible due to the invasiveness of the procedure, therefore experimental studies are in demand. The aim of the study was to carry-out immunohistochemical analysis of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in the left ventricle myocardium of preterm rats from the 1st to the 14th day of the postnatal period. Material and methods. The objects of the study were the hearts of full-term (n=15) and preterm (n=15) male Wistar rats. Hearts were fixed in buffered (pH 7.4) 10% formalin solution. The material was embedded in paraffin. MMP-9 and TIMP-1 were detected on sections using the immunohistochemical indirect peroxidase method with antibodies. The intensity of the immunohistochemical reaction was assessed semi-quantitatively (in points). The obtained data were processed using nonparametric statistics methods. Results. No differences were found in the localization of MMP-9- and TIMP-1-positive staining in the myocardium of preterm and full-term animals. In preterm rats on the 7th day of the postnatal period, the intensity of staining for both MMP-9 and TIMP-1 was reduced. On the 14th day of the postnatal period in the myocardium of preterm rats an increase in the intensity of the immunohistochemical reaction to MMP-9 was observed against the background of a low-intensity reaction to TIMP-1. Conclusion. The results of the study indicate a possible increase in the effects of MMP-9 in the myocardium of preterm animals on the 14th day of the postnatal period. Imbalance of MMP-9 and TIMP-1 may contribute to left ventricular myocardial remodeling in preterm animals.  

миокардпреждевременное рождениематриксная металлопротеиназа-9тканевый ингибитор матриксной металлопротеиназы-1иммуногистохимияmyocardiumpreterm birthmatrix metalloproteinase-9tissue inhibitor of matrix metalloproteinase-1immunohistochemistryИсследование выполнено при финансовой поддержке Российского научного фонда (проект № 24-25-00015).The study was carried out with the financial support of the Russian Scientific Foundation (project 24-25-00015).ReferencesИванова В.В., Мильто И.В., Серебрякова О.Н., Суходоло И.В. Выявление матриксных металлопротеиназ в сердце преждевременно рожденных крыс. Известия РАН. Серия биологическая. 2022;6:642–8.Ivanova VV, Milto IV, Serebryakova ON, Sukhodolo IV. Matrix Metalloproteinases detection in the heart of preterm rats. Izvestija RAN. Serija biologicheskaja. 2022;6:642–8 (In Russ.). doi: 10.31857/S1026347022060075Цорин И.Б. Статистическая обработка результатов фармакологических экспериментов, измеренных в порядковых и количественных шкалах, при невозможности анализа с помощью параметрических методов. Фармакокинетика и Фармакодинамика. 2020;(3):3-24.Tsorin IB. Statistical processing of pharmacological experiments results measured in ordinal and quantitative scales, if it is impossible to analyze using parametric methods. Pharmacokinetics and Pharmacodynamics. 2020 Jun 22;(3):3–24 (In Russ.). doi: 10.37489/2587-7836-2020-3-3-24Bellafiore M, Battaglia G, Bianco A, Farina F, Palma A, Paoli A. The involvement of MMP-2 and MMP-9 in heart exercise-related angiogenesis. Journal of Translational Medicine. 2013;11(1):283. doi: 10.1186/1479-5876-11-283Bellafiore M, Battaglia G, Bianco A, Farina F, Palma A, Paoli A. The involvement of MMP-2 and MMP-9 in heart exercise-related angiogenesis. Journal of Translational Medicine. 2013;11(1):283. doi: 10.1186/1479-5876-11-283Benny M, Hernandez D, Sharma M, Yousefi K, Shathiyah Kulandavelu, Sunil Batlahally, et al. Neonatal hyperoxia exposure induces aortic biomechanical alterations and cardiac dysfunction in juvenile rats. Physiological Reports. 2020 Jan 1;8(1):e14334. doi: 10.14814/phy2.14334Benny M, Hernandez D, Sharma M, Yousefi K, Shathiyah Kulandavelu, Sunil Batlahally, et al. Neonatal hyperoxia exposure induces aortic biomechanical alterations and cardiac dysfunction in juvenile rats. Physiological Reports. 2020 Jan 1;8(1):e14334. doi: 10.14814/phy2.14334Bertagnolli M, Huyard F, Cloutier A, Anstey Z, Huot-Marchand JÉ, Fallaha C, et al. Transient Neonatal High Oxygen Exposure Leads to Early Adult Cardiac Dysfunction, Remodeling, and Activation of the Renin–Angiotensin System. Hypertension. 2014 Jan;63(1):143–50. doi: 10.1161/HYPERTENSIONAHA.113.01760Bertagnolli M, Huyard F, Cloutier A, Anstey Z, Huot-Marchand JÉ, Fallaha C, et al. Transient Neonatal High Oxygen Exposure Leads to Early Adult Cardiac Dysfunction, Remodeling, and Activation of the Renin–Angiotensin System. Hypertension. 2014 Jan;63(1):143–50. doi: 10.1161/HYPERTENSIONAHA.113.01760Bigg HF, Rowan AD, Barker MD, Cawston TE. Activity of matrix metalloproteinase-9 against native collagen types I and III. The FEBS Journal. 2007 Feb 2;274(5):1246–55. doi: 10.1111/j.1742-4658.2007.05669.xBigg HF, Rowan AD, Barker MD, Cawston TE. Activity of matrix metalloproteinase-9 against native collagen types I and III. The FEBS Journal. 2007 Feb 2;274(5):1246–55. doi: 10.1111/j.1742-4658.2007.05669.xCabral-Pacheco GA, Garza-Veloz I, Castruita-De la Rosa C, Ramirez-Acuña JM, Perez-Romero BA, Guerrero-Rodriguez JF, et al. The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases. International Journal of Molecular Sciences. 2020 Dec 20;21(24):9739. doi: 10.3390/ijms21249739Cabral-Pacheco GA, Garza-Veloz I, Castruita-De la Rosa C, Ramirez-Acuña JM, Perez-Romero BA, Guerrero-Rodriguez JF, et al. The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases. International Journal of Molecular Sciences. 2020 Dec 20;21(24):9739. doi: 10.3390/ijms21249739Cadepond F, Ulmann A, Baulieu EE. RU486 (mifepristone): mechanisms of action and clinical uses. Annu Rev Med. 1997;48:129–56. doi: 10.1146/annurev.med.48.1.129Cadepond F, Ulmann A, Baulieu EE. RU486 (mifepristone): mechanisms of action and clinical uses. Annu Rev Med. 1997;48:129–56. doi: 10.1146/annurev.med.48.1.129Choi SH, Cho YS, Kim MJ, Lee CH, Seong Hwan-Hoo, Baek Soon Hwa, et al. Studies on the induction of pregnancy and the number of fetuses during pregnancy in rats. Journal of animal reproduction & biotechnology. 2020 Sep 30;35(3):232–8. doi: 10.12750/JARB.35.3.232Choi SH, Cho YS, Kim MJ, Lee CH, Seong Hwan-Hoo, Baek Soon Hwa, et al. Studies on the induction of pregnancy and the number of fetuses during pregnancy in rats. Journal of animal reproduction & biotechnology. 2020 Sep 30;35(3):232–8. doi: 10.12750/JARB.35.3.232Crump C, Howell EA, Stroustrup A, McLaughlin MA, Sundquist J, Sundquist K. Association of Preterm Birth With Risk of Ischemic Heart Disease in Adulthood. JAMA Pediatrics. 2019 Aug 1;173(8):736–43. doi: 10.1001/jamapediatrics.2019.1327Crump C, Howell EA, Stroustrup A, McLaughlin MA, Sundquist J, Sundquist K. Association of Preterm Birth With Risk of Ischemic Heart Disease in Adulthood. JAMA Pediatrics. 2019 Aug 1;173(8):736–43. doi: 10.1001/jamapediatrics.2019.1327Elhewala AA, Sanad M, Soliman AM, Sami MM, Ahmed AA. Matrix metalloproteinase-9 in pediatric rheumatic heart disease with and without heart failure. Biomed Rep. 2021 Jan;14(1):4. doi: 10.3892/br.2020.1380Elhewala AA, Sanad M, Soliman AM, Sami MM, Ahmed AA. Matrix metalloproteinase-9 in pediatric rheumatic heart disease with and without heart failure. Biomed Rep. 2021 Jan;14(1):4. doi: 10.3892/br.2020.1380Hamano YH, Zeisberg M, Sugimoto H, Lively JC, Yohei Maeshima, Yang C, et al. Physiological levels of tumstatin, a fragment of collagen IV α3 chain, are generated by MMP-9 proteolysis and suppress angiogenesis via αVβ3integrin. Cancer Cell. 2003 Jun 1;3(6):589–601.Hamano YH, Zeisberg M, Sugimoto H, Lively JC, Yohei Maeshima, Yang C, et al. Physiological levels of tumstatin, a fragment of collagen IV α3 chain, are generated by MMP-9 proteolysis and suppress angiogenesis via αVβ3integrin. Cancer Cell. 2003 Jun 1;3(6):589–601.Heikkilä K, Pulakka A, Metsälä J, Alenius S, Hovi P, Gissler M, et al. Preterm birth and the risk of chronic disease multimorbidity in adolescence and early adulthood: A population-based cohort study. Jacobsen R, editor. PLOS ONE. 2021 Dec 31;16(12):e0261952.Heikkilä K, Pulakka A, Metsälä J, Alenius S, Hovi P, Gissler M, et al. Preterm birth and the risk of chronic disease multimorbidity in adolescence and early adulthood: A population-based cohort study. Jacobsen R, editor. PLOS ONE. 2021 Dec 31;16(12):e0261952.Ishikawa J, Hirose H, Ishikawa S. Tissue Inhibitor of Matrix Metalloproteinase 1 Increases With Ageing and Can Be Associated With Stroke - Nested Case-Control Study –. Circulation Reports. 2019 Nov 8;1(11):502–7. doi: 10.1253/circrep.CR-19-0084Ishikawa J, Hirose H, Ishikawa S. Tissue Inhibitor of Matrix Metalloproteinase 1 Increases With Ageing and Can Be Associated With Stroke - Nested Case-Control Study –. Circulation Reports. 2019 Nov 8;1(11):502–7. doi: 10.1253/circrep.CR-19-0084Iyer RP, de Castro Brás LE, Jin YF, Lindsey ML. Translating Koch's postulates to identify matrix metalloproteinase roles in postmyocardial infarction remodeling: cardiac metalloproteinase actions (CarMA) postulates. Circ Res. 2014 Feb 28;114(5):860–71. doi: 10.1161/CIRCRESAHA.114.301673Iyer RP, de Castro Brás LE, Jin YF, Lindsey ML. Translating Koch's postulates to identify matrix metalloproteinase roles in postmyocardial infarction remodeling: cardiac metalloproteinase actions (CarMA) postulates. Circ Res. 2014 Feb 28;114(5):860–71. doi: 10.1161/CIRCRESAHA.114.301673Kumar VHS. Cardiovascular morbidities in adults born preterm: getting to the heart of the matter! Children (Basel). 2022;9(12):1843. doi: 10.3390/children9121843Kumar VHS. Cardiovascular morbidities in adults born preterm: getting to the heart of the matter! Children (Basel). 2022;9(12):1843. doi: 10.3390/children9121843Lê B, Dahl MJ, Albertine KH, Sutherland MR, Black MJ. Preterm Birth With Neonatal Interventions Accelerates Collagen Deposition in the Left Ventricle of Lambs Without Affecting Cardiomyocyte Development. CJC Open. 2021 May;3(5):574 – doi: 10.1016/j.cjco.2020.12.017Lê B, Dahl MJ, Albertine KH, Sutherland MR, Black MJ. Preterm Birth With Neonatal Interventions Accelerates Collagen Deposition in the Left Ventricle of Lambs Without Affecting Cardiomyocyte Development. CJC Open. 2021 May;3(5):574 – doi: 10.1016/j.cjco.2020.12.017Liu Y, Zhang H, Yan L, Du W, Zhang M, Chen H, et al. MMP-2 and MMP-9 contribute to the angiogenic effect produced by hypoxia/15-HETE in pulmonary endothelial cells. Journal of Molecular and Cellular Cardiology. 2018 Aug 1;121:36–50. doi: 10.1016/j.yjmcc.2018.06.006Liu Y, Zhang H, Yan L, Du W, Zhang M, Chen H, et al. MMP-2 and MMP-9 contribute to the angiogenic effect produced by hypoxia/15-HETE in pulmonary endothelial cells. Journal of Molecular and Cellular Cardiology. 2018 Aug 1;121:36–50. doi: 10.1016/j.yjmcc.2018.06.006Ma Y, Iyer RP, Jung M, Czubryt MP, Lindsey ML. Cardiac Fibroblast Activation Post-Myocardial Infarction: Current Knowledge Gaps. Trends in Pharmacological Sciences. 2017 May;38(5):448 – doi: 10.1016/j.tips.2017.03.001Ma Y, Iyer RP, Jung M, Czubryt MP, Lindsey ML. Cardiac Fibroblast Activation Post-Myocardial Infarction: Current Knowledge Gaps. Trends in Pharmacological Sciences. 2017 May;38(5):448 – doi: 10.1016/j.tips.2017.03.001Mohlkert L, Hallberg J, Broberg O, Rydberg A, Halvorsen CP, Liuba P, et al. The Preterm Heart in Childhood: Left Ventricular Structure, Geometry, and Function Assessed by Echocardiography in 6-Year-Old Survivors of Periviable Births. Journal of the American Heart Association. 2018 Jan 23;7(2).Mohlkert L, Hallberg J, Broberg O, Rydberg A, Halvorsen CP, Liuba P, et al. The Preterm Heart in Childhood: Left Ventricular Structure, Geometry, and Function Assessed by Echocardiography in 6-Year-Old Survivors of Periviable Births. Journal of the American Heart Association. 2018 Jan 23;7(2).Morishita T, Uzui H, Mitsuke Y, Amaya N, Kaseno K, Ishida K, et al. Association between matrix metalloproteinase-9 and worsening heart failure events in patients with chronic heart failure. ESC Heart Failure. 2017 Feb 10;4(3):321–30. doi: 10.1002/ehf2.12137Morishita T, Uzui H, Mitsuke Y, Amaya N, Kaseno K, Ishida K, et al. Association between matrix metalloproteinase-9 and worsening heart failure events in patients with chronic heart failure. ESC Heart Failure. 2017 Feb 10;4(3):321–30. doi: 10.1002/ehf2.12137Nandi SS, Katsurada K, Sharma NM, Anderson DR, Mahata SK, Patel KP. MMP9 inhibition increases autophagic flux in chronic heart failure. American Journal of Physiology Heart and Circulatory Physiology. 2020 Dec 1;319(6):H1414–37. doi: 10.1152/ajpheart.00032.2020Nandi SS, Katsurada K, Sharma NM, Anderson DR, Mahata SK, Patel KP. MMP9 inhibition increases autophagic flux in chronic heart failure. American Journal of Physiology Heart and Circulatory Physiology. 2020 Dec 1;319(6):H1414–37. doi: 10.1152/ajpheart.00032.2020Nobile S, Di Sipio Morgia C, Vento G. Perinatal Origins of Adult Disease and Opportunities for Health Promotion: A Narrative Review. Journal of Personalized Medicine. 2022 Jan 25;12(2):157. doi: 10.3390/jpm12020157Nobile S, Di Sipio Morgia C, Vento G. Perinatal Origins of Adult Disease and Opportunities for Health Promotion: A Narrative Review. Journal of Personalized Medicine. 2022 Jan 25;12(2):157. doi: 10.3390/jpm12020157Pang C, Wu X, Ren L, Wang X, Hong L. Changes and significance of serum Copeptin and MMP-9 in children with chronic heart failure. Journal of Clinical Pediatrics. 2018;2:432–7.Pang C, Wu X, Ren L, Wang X, Hong L. Changes and significance of serum Copeptin and MMP-9 in children with chronic heart failure. Journal of Clinical Pediatrics. 2018;2:432–7.Saadat S, Noureddini M, Mahjoubin-Tehran M, Nazemi S, Shojaie L, Aschner M, et al. Pivotal Role of TGF-β/Smad Signaling in Cardiac Fibrosis: Non-coding RNAs as Effectual Players. Frontiers in Cardiovascular Medicine. 2021 Jan 25;7:588347. doi: 10.3389/fcvm.2020.588347Saadat S, Noureddini M, Mahjoubin-Tehran M, Nazemi S, Shojaie L, Aschner M, et al. Pivotal Role of TGF-β/Smad Signaling in Cardiac Fibrosis: Non-coding RNAs as Effectual Players. Frontiers in Cardiovascular Medicine. 2021 Jan 25;7:588347. doi: 10.3389/fcvm.2020.588347Schuermans A, Lewandowski AJ. Understanding the preterm human heart: What do we know so far? The Anatomical Record. 2022 Feb 9;305(9):2099–112. doi: 10.1002/ar.24875Schuermans A, Lewandowski AJ. Understanding the preterm human heart: What do we know so far? The Anatomical Record. 2022 Feb 9;305(9):2099–112. doi: 10.1002/ar.24875Schulz CG, Sawicki G, Lemke RP, Roeten BM, Schulz R, Cheung PY. MMP-2 and MMP-9 and Their Tissue Inhibitors in the Plasma of Preterm and Term Neonates. Pediatric research. 2004 May 1;55(5):794–801. doi: 10.1203/01.PDR.0000120683.68630.FBSchulz CG, Sawicki G, Lemke RP, Roeten BM, Schulz R, Cheung PY. MMP-2 and MMP-9 and Their Tissue Inhibitors in the Plasma of Preterm and Term Neonates. Pediatric research. 2004 May 1;55(5):794–801. doi: 10.1203/01.PDR.0000120683.68630.FBSissman NJ. Developmental landmarks in cardiac morphogenesis: Comparative chronology. The American Journal of Cardiology. 1970 Feb;25(2):141–8. doi: 10.1016/0002-9149(70)90575-8Sissman NJ. Developmental landmarks in cardiac morphogenesis: Comparative chronology. The American Journal of Cardiology. 1970 Feb;25(2):141–8. doi: 10.1016/0002-9149(70)90575-8Strilakou A, Perelas A, Lazaris A, Papavdi A, Karkalousos P, Giannopoulou I, et al. Immunohistochemical determination of the extracellular matrix modulation in a rat model of choline-deprived myocardium: the effects of carnitine. Fundamental & clinical pharmacology. 2015 Dec 8;30(1):47 – doi: 10.1111/fcp.12163Strilakou A, Perelas A, Lazaris A, Papavdi A, Karkalousos P, Giannopoulou I, et al. Immunohistochemical determination of the extracellular matrix modulation in a rat model of choline-deprived myocardium: the effects of carnitine. Fundamental & clinical pharmacology. 2015 Dec 8;30(1):47 – doi: 10.1111/fcp.12163Tan CMJ, Lewandowski AJ. The transitional heart: From early embryonic and fetal development to neonatal life. Fetal Diagnosis and Therapy. 2019 Sep 18;47(5):1–14. doi: 10.1159/000501906Tan CMJ, Lewandowski AJ. The transitional heart: From early embryonic and fetal development to neonatal life. Fetal Diagnosis and Therapy. 2019 Sep 18;47(5):1–14. doi: 10.1159/000501906Telles F, McNamara N, Nanayakkara S, Doyle MP, Williams M, Yaeger L, et al. Changes in the Preterm Heart From Birth to Young Adulthood: A Meta-analysis. Pediatrics. 2020 Aug 1;146(2):e20200146. doi: 10.1542/peds.2020-0146Telles F, McNamara N, Nanayakkara S, Doyle MP, Williams M, Yaeger L, et al. Changes in the Preterm Heart From Birth to Young Adulthood: A Meta-analysis. Pediatrics. 2020 Aug 1;146(2):e20200146. doi: 10.1542/peds.2020-0146Wang Y, Xu F, Chen JM, Shen X, Deng Y, Xu L, et al. Matrix metalloproteinase-9 induces cardiac fibroblast migration, collagen and cytokine secretion: Inhibition by salvianolic acid B from Salvia miltiorrhiza. Phytomedicine. 2011 Dec 1;19(1):13 – doi: 10.1016/j.phymed.2011.06.024Wang Y, Xu F, Chen JM, Shen X, Deng Y, Xu L, et al. Matrix metalloproteinase-9 induces cardiac fibroblast migration, collagen and cytokine secretion: Inhibition by salvianolic acid B from Salvia miltiorrhiza. Phytomedicine. 2011 Dec 1;19(1):13 – doi: 10.1016/j.phymed.2011.06.024Yadav SK, Kambis TN, Kar S, Park SY, Mishra PK. MMP9 mediates acute hyperglycemia-induced human cardiac stem cell death by upregulating apoptosis and pyroptosis in vitro. Cell Death & Disease. 2020 Mar;11(3):186. doi: 10.1038/s41419-020-2367-6Yadav SK, Kambis TN, Kar S, Park SY, Mishra PK. MMP9 mediates acute hyperglycemia-induced human cardiac stem cell death by upregulating apoptosis and pyroptosis in vitro. Cell Death & Disease. 2020 Mar;11(3):186. doi: 10.1038/s41419-020-2367-6Yan Y, Jiang L, Li M, Zhang H, Shen Y, Zhang W, et al. Levels of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 are related to cardiopulmonary injury in fetal inflammatory response syndrome. Clinics. 2020 Jan 1;75:e2049. doi: 10.6061/clinics/2020/e2049Yan Y, Jiang L, Li M, Zhang H, Shen Y, Zhang W, et al. Levels of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 are related to cardiopulmonary injury in fetal inflammatory response syndrome. Clinics. 2020 Jan 1;75:e2049. doi: 10.6061/clinics/2020/e2049Yu Q, Stamenkovic I. Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. PubMed. 2000 Jan 15;14(2):163–76.Yu Q, Stamenkovic I. Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. PubMed. 2000 Jan 15;14(2):163–76.

The authors declare that there are no conflicts of interest present.