{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T22:56:54Z","timestamp":1784761014819,"version":"3.55.0"},"reference-count":79,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T00:00:00Z","timestamp":1669161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006356","name":"University of Southern Denmark","doi-asserted-by":"publisher","award":["120661"],"award-info":[{"award-number":["120661"]}],"id":[{"id":"10.13039\/501100006356","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006356","name":"University of Southern Denmark","doi-asserted-by":"publisher","award":["PN-III-P4-PCE-2021-1680"],"award-info":[{"award-number":["PN-III-P4-PCE-2021-1680"]}],"id":[{"id":"10.13039\/501100006356","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Romanian Ministry of Education and Research","award":["120661"],"award-info":[{"award-number":["120661"]}]},{"name":"Romanian Ministry of Education and Research","award":["PN-III-P4-PCE-2021-1680"],"award-info":[{"award-number":["PN-III-P4-PCE-2021-1680"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Myocardial infarction is remains the leading cause of death in developed countries. Recent data show that the composition of the extracellular matrix might differ despite similar heart function and infarction sizes. Because collagen is the main component of the extracellular matrix, we hypothesized that changes in inflammatory cell recruitment influence the synthesis of different collagen subtypes in myofibroblasts, thus changing the composition of the scar. We found that neutrophils sustain the proliferation of fibroblasts, remodeling, differentiation, migration and inflammation, predominantly by IL-1 and PPAR\u03b3 pathways (n = 3). They also significantly inhibit the mRNA expression of fibrillar collagen, maintaining a reduced stiffness in isolated myofibroblasts (n = 4\u20135). Reducing the neutrophil infiltration in CCR1\u2212\/\u2212 resulted in increased mRNA expression of collagen 11, moderate expression of collagen 19 and low expression of collagen 13 and 26 in the scar 4 weeks post infarction compared with other groups (n = 3). Mononuclear cells increased the synthesis of all collagen subtypes and upregulated the NF-kB, angiotensin II and PPAR\u03b4 pathways (n = 3). They increased the synthesis of collagen subtypes 1, 3, 5, 16 and 23 but reduced the expression of collagens 5 and 16 (n = 3). CCR2\u2212\/\u2212 scar tissue showed higher levels of collagen 13 (n = 3), in association with a significant reduction in stiffness (n = 4\u20135). Upregulation of the inflammation-related genes in myofibroblasts mostly modulated the fibrillar collagen subtypes, with less effect on the FACIT, network-forming and globular subtypes (n = 3). The upregulation of proliferation and differentiation genes in myofibroblasts seemed to be associated only with the fibrillar collagen subtype, whereas angiogenesis-related genes are associated with fibrillar, network-forming and multiplexin subtypes. In conclusion, although we intend for our findings to deepen the understanding of the mechanism of healing after myocardial infarction and scar formation, the process of collagen synthesis is highly complex, and further intensive investigation is needed to put together all the missing puzzle pieces in this still incipient knowledge process.<\/jats:p>","DOI":"10.3390\/ijms232314571","type":"journal-article","created":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T02:10:54Z","timestamp":1669169454000},"page":"14571","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Endogenous Modulation of Extracellular Matrix Collagen during Scar Formation after Myocardial Infarction"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2308-6543","authenticated-orcid":false,"given":"David","family":"Schumacher","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, University Hospital, RWTH Aachen University, 52074 Aachen, Germany"},{"name":"Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, 52074 Aachen, Germany"},{"name":"Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adelina","family":"Curaj","sequence":"additional","affiliation":[{"name":"Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany"},{"name":"Department for Cardiology, Angiology and Internal Intensive Care, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mareike","family":"Staudt","sequence":"additional","affiliation":[{"name":"Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakine","family":"Simsekyilmaz","sequence":"additional","affiliation":[{"name":"Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Kanzler","sequence":"additional","affiliation":[{"name":"Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9921-4284","authenticated-orcid":false,"given":"Peter","family":"Boor","sequence":"additional","affiliation":[{"name":"Institute for Pathology, RWTH Aachen University, 52074 Aachen, Germany"},{"name":"Division of Nephrology and Clinical Immunology, RWTH Aachen University, 52074 Aachen, Germany"},{"name":"Institute of Molecular Biomedicine, Comenius University, 811 08 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1566-7129","authenticated-orcid":false,"given":"Barbara Mara","family":"Klinkhammer","sequence":"additional","affiliation":[{"name":"Institute for Pathology, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Li","sequence":"additional","affiliation":[{"name":"Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8501-588X","authenticated-orcid":false,"given":"Octavian","family":"Bucur","sequence":"additional","affiliation":[{"name":"\u201cVictor Babes\u201d National Institute of Pathology, 050096 Bucharest, Romania"},{"name":"Viron Molecular Medicine Institute, 1 Boston Place, Ste 2600, Boston, MA 02108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adnan","family":"Kaabi","sequence":"additional","affiliation":[{"name":"Department for Cardiology, Angiology and Internal Intensive Care, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yichen","family":"Xu","sequence":"additional","affiliation":[{"name":"Department for Cardiology, Angiology and Internal Intensive Care, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany"},{"name":"Institute for Molecular Medicine, University of Southern Denmark, 5230 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6325-6167","authenticated-orcid":false,"given":"Huabo","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department for Cardiology, Angiology and Internal Intensive Care, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany"},{"name":"Institute for Molecular Medicine, University of Southern Denmark, 5230 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pakhwan","family":"Nilcham","sequence":"additional","affiliation":[{"name":"Department for Cardiology, Angiology and Internal Intensive Care, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Schuh","sequence":"additional","affiliation":[{"name":"Department for Cardiology, Angiology and Internal Intensive Care, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaela","family":"Rusu","sequence":"additional","affiliation":[{"name":"Department for Cardiology, Angiology and Internal Intensive Care, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa A.","family":"Liehn","sequence":"additional","affiliation":[{"name":"Department for Cardiology, Angiology and Internal Intensive Care, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany"},{"name":"\u201cVictor Babes\u201d National Institute of Pathology, 050096 Bucharest, Romania"},{"name":"Institute for Molecular Medicine, University of Southern Denmark, 5230 Odense, Denmark"},{"name":"National Heart Center Singapore, 5 Hospital Dr., Singapore 169609, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16744","DOI":"10.1038\/s41598-019-53351-7","article-title":"Biomechanical assessment of remote and postinfarc-tion scar remodeling following myocardial infarction","volume":"9","author":"Rusu","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e142","DOI":"10.15190\/d.2022.1","article-title":"New model pre-dicts in-hospital complications in myocardial infarction","volume":"10","year":"2022","journal-title":"Discoveries"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.yjmcc.2009.07.015","article-title":"The extracellular matrix as a modulator of the inflammatory and reparative response following myocardial infarction","volume":"48","author":"Dobaczewski","year":"2010","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2357","DOI":"10.1016\/j.jacc.2011.08.034","article-title":"Repair after myocardial infarction, between fantasy and reality: The role of chemo-kines","volume":"58","author":"Liehn","year":"2011","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_5","first-page":"1113","article-title":"Myofibroblasts and the extracellular matrix network in post-myocardial infarction cardiac remodeling","volume":"466","author":"Ma","year":"2014","journal-title":"Pflug. Arch. Eur. J. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Curaj, A., Schumacher, D., Rusu, M., Staudt, M., Li, X., Simsekyilmaz, S., Jankowski, V., Jankowski, J., Dumitra\u015fcu, A.R., and Hausenloy, D.J. (2020). Neutrophils Modulate Fibroblast Function and Promote Healing and Scar Formation after Murine Myocardial Infarction. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21103685"},{"key":"ref_7","first-page":"325","article-title":"Collagen remodeling after myocardial infarction in the rat heart","volume":"147","author":"Cleutjens","year":"1995","journal-title":"Am. J. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1016\/j.biocel.2007.12.005","article-title":"Fragments of extracellular matrix as mediators of inflammation","volume":"40","author":"Senior","year":"2008","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/S1050-1738(98)00028-0","article-title":"Fibronectin\u2013Fibrin Cross-Linking: A Regulator of Cell Behavior","volume":"8","author":"Corbett","year":"1998","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1172\/JCI109926","article-title":"Chemotactic activity of elastin-derived peptides","volume":"66","author":"Senior","year":"1980","journal-title":"J. Clin. Investig."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"H221","DOI":"10.1152\/ajpheart.00495.2009","article-title":"Evolution of scar structure, mechanics, and ventricular function after myocardial infarction in the rat","volume":"298","author":"Fomovsky","year":"2010","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1016\/j.yjmcc.2012.02.012","article-title":"Regional mechanics determine collagen fiber structure in healing myocardial infarcts","volume":"52","author":"Fomovsky","year":"2012","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/bs.ctdb.2018.02.004","article-title":"Collagen Fibril Assembly and Function","volume":"130","author":"Holmes","year":"2018","journal-title":"Curr. Top. Dev. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1146\/annurev.bioeng.7.060804.100453","article-title":"Structure and Mechanics of Healing Myocardial Infarcts","volume":"7","author":"Holmes","year":"2005","journal-title":"Annu. Rev. Biomed. Eng."},{"key":"ref_15","first-page":"377","article-title":"Expression of tenascin by vascular smooth muscle cells. Alterations in hypertensive rats and stimulation by angiotensin II","volume":"141","author":"Mackie","year":"1992","journal-title":"Am. J. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1084\/jem.20081244","article-title":"Absence of SPARC results in increased cardiac rupture and dysfunction after acute myocardial infarction","volume":"206","author":"Schellings","year":"2008","journal-title":"J. Exp. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"i7","DOI":"10.1083\/JCB1802OIA7","article-title":"Periostin is essential for cardiac healing after acute myocardial infarction","volume":"180","author":"Shimazaki","year":"2008","journal-title":"J. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1161\/hh1001.090842","article-title":"Exaggerated Left Ventricular Dilation and Reduced Collagen Deposition after Myocardial Infarction in Mice Lacking Osteopontin","volume":"88","author":"Trueblood","year":"2001","journal-title":"Circ. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e9","DOI":"10.15190\/d.2014.1","article-title":"Novel insights into the mechanism of cell-based therapy after chronic myocardial infarction","volume":"2","author":"Schuh","year":"2014","journal-title":"Discoveries"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.2174\/13816128113199990443","article-title":"Effect of SDF-1 \u03b1 on Endogenous Mobilized and Transplanted Stem Cells in Regeneration after Myocardial Infarction","volume":"20","author":"Schuh","year":"2014","journal-title":"Curr. Pharm. Des."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2311","DOI":"10.1111\/j.1582-4934.2012.01539.x","article-title":"Myocardial regeneration by transplantation of modified endothelial progenitor cells expressing SDF-1 in a rat model","volume":"16","author":"Schuh","year":"2012","journal-title":"J. Cell. Mol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1089\/1076327041348491","article-title":"Transplantation of fetal cardiomyocytes into in-farcted rat hearts results in long-term functional improvement","volume":"10","author":"Skobel","year":"2004","journal-title":"Tissue Eng."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1007\/s00395-005-0516-9","article-title":"Transplantation of human umbilical vein en-dothelial cells improves left ventricular function in a rat model of myocardial infarction","volume":"100","author":"Merx","year":"2005","journal-title":"Basic Res. Cardiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s00395-007-0685-9","article-title":"Transplantation of endothelial progenitor cells im-proves neovascularization and left ventricular function after myocardial infarction in a rat model","volume":"103","author":"Schuh","year":"2008","journal-title":"Basic Res. Cardiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1111\/j.1582-4934.2007.00194.x","article-title":"Ccr1 deficiency reduces inflamma-tory remodelling and preserves left ventricular function after myocardial infarction","volume":"12","author":"Liehn","year":"2008","journal-title":"J. Cell Mol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2415","DOI":"10.1016\/j.jacc.2011.08.033","article-title":"Double-edged role of the CXCL12\/CXCR4 axis in experimental myocardial infarction","volume":"58","author":"Liehn","year":"2011","journal-title":"J. Am. Coll Cardiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1007\/s00395-008-0763-7","article-title":"Improved left ventricular function after transplantation of microspheres and fibroblasts in a rat model of myocardial infarction","volume":"104","author":"Schuh","year":"2009","journal-title":"Basic Res. Cardiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1161\/CIRCULATIONAHA.106.646091","article-title":"Critical role of monocyte chemoattractant pro-tein-1\/CC chemokine ligand 2 in the pathogenesis of ischemic cardiomyopathy","volume":"115","author":"Frangogiannis","year":"2007","journal-title":"Circulation"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1161\/01.RES.0000163017.13772.3a","article-title":"CCL2\/Monocyte Chemoattractant Pro-tein-1 regulates inflammatory responses critical to healing myocardial infarcts","volume":"96","author":"Dewald","year":"2005","journal-title":"Circ. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/s41578-020-0213-1","article-title":"Collagen: Quantification, biomechanics and role of minor subtypes in cartilage","volume":"5","author":"Bielajew","year":"2020","journal-title":"Nat. Rev. Mater."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.2353\/ajpath.2010.090759","article-title":"CCR5 Signaling Suppresses Inflammation and Reduces Adverse Remodeling of the Infarcted Heart, Mediating Recruitment of Regulatory T Cells","volume":"176","author":"Dobaczewski","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3037","DOI":"10.1084\/jem.20070885","article-title":"The healing myocardium se-quentially mobilizes two monocyte subsets with divergent and complementary functions","volume":"204","author":"Nahrendorf","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"16060","DOI":"10.1021\/la302706b","article-title":"Quantitative Mapping of the Elastic Modulus of Soft Materials with HarmoniX and PeakForce QNM AFM Modes","volume":"28","author":"Dokukin","year":"2012","journal-title":"Langmuir"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.bbrc.2021.04.088","article-title":"Distinctive roles of fibrillar collagen I and collagen III in mediating fibro-blast-matrix interaction: A nanoscopic study","volume":"560","author":"Li","year":"2021","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1093\/cvr\/cvaa324","article-title":"Cardiac fibrosis","volume":"117","author":"Frangogiannis","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.addr.2021.03.021","article-title":"Cardiac fibrosis: Myofibroblast-mediated pathological regulation and drug delivery strategies","volume":"173","author":"Liu","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.mam.2018.06.003","article-title":"Organ and tissue fibrosis: Molecular signals, cellular mechanisms and translational implications","volume":"65","author":"Weiskirchen","year":"2018","journal-title":"Mol. Asp. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/s11886-022-01647-y","article-title":"Role of Cardiac Fibroblasts in Cardiac Injury and Repair","volume":"24","author":"Han","year":"2022","journal-title":"Curr. Cardiol. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"109824","DOI":"10.1016\/j.cellsig.2020.109824","article-title":"Fibroblast contributions to ischemic cardiac remodeling","volume":"77","author":"Burke","year":"2020","journal-title":"Cell. Signal."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1016\/j.bbamcr.2019.06.001","article-title":"The complex dynamics of myocardial interstitial fibrosis in heart failure. Focus on collagen cross-linking","volume":"1866","author":"Gonzalez","year":"2019","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1111\/imr.12971","article-title":"The inflammatory speech of fibroblasts","volume":"302","author":"Schuster","year":"2021","journal-title":"Immunol. Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1177\/002215540205000108","article-title":"Morphological characteristics of the microvasculature in healing myocardial infarcts","volume":"50","author":"Ren","year":"2002","journal-title":"J. Histochem. Cytochem."},{"key":"ref_43","unstructured":"Camargo, R.O., Abual\u2019Anaz, B., Rattan, S.G., Filomeno, K.L., and Dixon, I.M.C. (2021). Novel factors that activate and deactivate cardiac fibroblasts: A new perspective for treatment of cardiac fibrosis. Wound Repair Regen."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.yjmcc.2013.11.003","article-title":"Origin, development, and differentiation of cardiac fibroblasts","volume":"70","author":"Lajiness","year":"2013","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Venugopal, H., Hanna, A., Humeres, C., and Frangogiannis, N.G. (2022). Properties and Functions of Fibroblasts and Myofibroblasts in Myocardial Infarction. Cells, 11.","DOI":"10.3390\/cells11091386"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Fu, X., Liu, Q., Li, C., Li, Y., and Wang, L. (2020). Cardiac Fibrosis and Cardiac Fibroblast Lineage-Tracing: Recent Advances. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.00416"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1038\/s41586-022-05060-x","article-title":"Spatial multi-omic map of human myocardial infarction","volume":"608","author":"Kuppe","year":"2022","journal-title":"Nature"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.addr.2017.07.014","article-title":"The good and the bad collagens of fibrosis\u2014Their role in signaling and organ function","volume":"121","author":"Karsdal","year":"2017","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_49","first-page":"28","article-title":"Fibril-associated collagens","volume":"11","author":"Dublet","year":"1990","journal-title":"Biomaterials"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/S0065-3233(05)70011-5","article-title":"Molecular Packing in Network-Forming Collagens","volume":"70","author":"Knupp","year":"2005","journal-title":"Adv. Protein Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/S0945-053X(03)00051-9","article-title":"Collagenous transmembrane proteins: Collagen XVII as a prototype","volume":"22","author":"Franzke","year":"2003","journal-title":"Matrix Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.ajpath.2011.09.033","article-title":"A collagen \u03b12(I) mutation impairs healing after experimental myocardial infarction","volume":"180","author":"Hofmann","year":"2012","journal-title":"Am. J. Pathol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1161\/CIRCRESAHA.111.252734","article-title":"Absence of type VI collagen par-adoxically improves cardiac function, structure, and remodeling after myocardial infarction","volume":"110","author":"Luther","year":"2012","journal-title":"Circ. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.yjmcc.2009.06.017","article-title":"Non-fibrillar collagens: Key mediators of post-infarction cardiac remodeling?","volume":"48","author":"Shamhart","year":"2010","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3295","DOI":"10.1002\/dvdy.20980","article-title":"ColVa1 and ColXIa1 are required for myocardial morphogen-esis and heart valve development","volume":"235","author":"Lincoln","year":"2006","journal-title":"Dev. Dyn."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/S0945-053X(00)00119-0","article-title":"Type XIII collagen: A novel cell adhesion component present in a range of cell\u2013matrix adhesions and in the intercalated discs between cardiac muscle cells","volume":"19","author":"Tuomisto","year":"2001","journal-title":"Matrix Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5153","DOI":"10.1093\/emboj\/20.18.5153","article-title":"Abnormal adherence junctions in the heart and reduced angiogenesis in transgenic mice overexpressing mutant type XIII collagen","volume":"20","author":"Sund","year":"2001","journal-title":"EMBO J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/j.yjmcc.2012.08.002","article-title":"Collagen XIV is important for growth and structural integrity of the myocardium","volume":"53","author":"Tao","year":"2012","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1161\/CIRCRESAHA.110.222133","article-title":"Collagen XV Is Necessary for Modeling of the Extracellular Matrix and Its Deficiency Predisposes to Cardiomyopathy","volume":"107","author":"Rasi","year":"2010","journal-title":"Circ. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1253\/circj.CJ-09-0486","article-title":"Inhibition of Endostatin\/Collagen XVIII Deteriorates Left Ventricular Remodeling and Heart Failure in Rat Myocardial Infarction Model","volume":"74","author":"Isobe","year":"2010","journal-title":"Circ. J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0040-8166(96)80004-8","article-title":"Tissue distribution and developmental expression of type XVI collagen in the mouse","volume":"28","author":"Lai","year":"1996","journal-title":"Tissue Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1536\/ihj.39.211","article-title":"Expression of Type XVII Collagen \u03b11 Chain mRNA in the Mouse Heart","volume":"39","author":"Kondo","year":"1998","journal-title":"Jpn. Hear. J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/S0014-5793(01)02754-5","article-title":"A new FACIT of the collagen family: COL21A1","volume":"505","author":"Fitzgerald","year":"2001","journal-title":"FEBS Lett."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"12791","DOI":"10.1074\/jbc.C700021200","article-title":"Collagen XXVII Is Developmentally Regulated and Forms Thin Fibrillar Structures Distinct from Those of Classical Vertebrate Fibrillar Collagens","volume":"282","author":"Plumb","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1038\/bjp.2008.21","article-title":"Agonists at PPAR-gamma suppress angiotensin II-induced production of plasminogen activator inhibitor-1 and extracellular matrix in rat cardiac fibroblasts","volume":"153","author":"Hao","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.cardiores.2007.04.026","article-title":"Activation of PPAR\u03b4 inhibits cardiac fibroblast proliferation and the transdifferentiation into myofibroblasts","volume":"75","author":"Teunissen","year":"2007","journal-title":"Cardiovasc. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e41","DOI":"10.15190\/d.2015.33","article-title":"Interleukin-1 in cardiac injury, repair, and remodeling: Pathophysiologic and translational concepts","volume":"3","author":"Frangogiannis","year":"2015","journal-title":"Discoveries"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"5719","DOI":"10.1074\/jbc.M107515200","article-title":"Transcription factor NF-kappa B is necessary for up-regulation of type 1 angiotensin II receptor mRNA in rat cardiac fibroblasts treated with tumor necrosis factor-\u03b1 or in-terleukin-1\u03b2","volume":"277","author":"Cowling","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2372","DOI":"10.1172\/JCI117243","article-title":"Characterization of angiotensin II receptors in cultured adult rat cardiac fibroblasts. Coupling to signaling systems and gene expression","volume":"93","author":"Crabos","year":"1994","journal-title":"J. Clin. Investig."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Curaj, A., Simsekyilmaz, S., Staudt, M., and Liehn, E. (2015). Minimal Invasive Surgical Procedure of Inducing Myocardial Infarction in Mice. J. Vis. Exp., e52197.","DOI":"10.3791\/52197-v"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e136","DOI":"10.15190\/d.2021.15","article-title":"Heart function assessment during aging in apolipoprotein E knock-out mice","volume":"9","author":"Liehn","year":"2021","journal-title":"Discoveries"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/1471-2199-9-102","article-title":"Characterization of housekeeping genes in zebrafish: Male-female differences and effects of tissue type, developmental stage and chemical treatment","volume":"9","author":"McCurley","year":"2008","journal-title":"BMC Mol. Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"66","DOI":"10.3389\/fmicb.2019.00066","article-title":"\u03b2-Actin: Not a Suitable Internal Control of Hepatic Fibrosis Caused by Schistosoma japonicum","volume":"10","author":"Zhang","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Veres-Szekely, A., Pap, D., Sziksz, E., J\u00e1vorszky, E., Rokonay, R., Lippai, R., Tory, K., Fekete, A., Tulassay, T., and Szab\u00f3, A.J. (2017). Selective measurement of \u03b1 smooth mus-cle actin: Why \u03b2-actin can not be used as a housekeeping gene when tissue fibrosis occurs. BMC Mol. Biol., 18.","DOI":"10.1186\/s12867-017-0089-9"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s11684-008-0045-7","article-title":"Effects of hypoxia on mRNA expression of housekeeping genes in rat brain tissue and primary cultured neural cells","volume":"2","author":"Yang","year":"2008","journal-title":"Front. Med. China"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1006\/bbrc.1999.0815","article-title":"Direct comparison of GAPDH, \u03b2-actin, cyclophilin, and 28S rRNA as internal standards for quanti-fying RNA levels under hypoxia","volume":"259","author":"Zhong","year":"1999","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/s00414-012-0787-2","article-title":"Apparent versus true gene expression changes of three hypoxia-related genes in autopsy derived tissue and the importance of normalisation","volume":"127","author":"Huth","year":"2012","journal-title":"Int. J. Leg. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"24492","DOI":"10.1038\/srep24492","article-title":"Titin stiffness modifies the force-generating region of muscle sarcomeres","volume":"6","author":"Li","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"D447","DOI":"10.1093\/nar\/gku1003","article-title":"STRING v10: Protein-protein inter-action networks, integrated over the tree of life","volume":"43","author":"Szklarczyk","year":"2015","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/23\/14571\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:24:44Z","timestamp":1760145884000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/23\/14571"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,23]]},"references-count":79,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijms232314571"],"URL":"https:\/\/doi.org\/10.3390\/ijms232314571","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,23]]}}}