{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T16:38:01Z","timestamp":1780850281943,"version":"3.54.1"},"reference-count":57,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"18","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,9,21]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Cardiac fibrosis is the excessive deposition of extracellular matrix in the heart, triggered by a cardiac insult, aging, genetics, or environmental factors. Molecular imaging of the cardiac extracellular matrix with targeted probes could improve diagnosis and treatment of heart disease. However, although this technology has been used to demonstrate focal scarring arising from myocardial infarction, its capacity to demonstrate extracellular matrix expansion and diffuse cardiac fibrosis has not been assessed.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">Here, we report the use of collagen\u2010targeted peptides labeled with near\u2010infrared fluorophores for the detection of diffuse cardiac fibrosis in the \u03b22\u2010AR (\u03b2\u20102\u2010adrenergic receptor) overexpressing mouse model and in ischemic human hearts. Two approaches were evaluated, the first based on a T peptide that binds matrix metalloproteinase\u20102\u2010proteolyzed collagen IV, and the second on the cyclic peptide EP\u20103533, which targets collagen I. The systemic and cardiac uptakes of both peptides (intravenously administered) were quantified ex vivo by near\u2010infrared imaging of whole organs, tissue sections, and heart lysates. The peptide accumulation profiles corresponded to an immunohistochemically\u2010validated increase in collagen types I and IV in hearts of transgenic mice versus littermate controls. The T peptide could encouragingly demonstrate both the intermediate (7 months old) and severe (11 months old) cardiomyopathic phenotypes. Co\u2010immunostainings of fluorescent peptides and collagens, as well as reduced collagen binding of a control peptide, confirmed the collagen specificity of the tracers. Qualitative analysis of heart samples from patients with ischemic cardiomyopathy compared with nondiseased donors supported the collagen\u2010enhancement capabilities of these peptides also in the clinical settings.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Together, these observations demonstrate the feasibility and translation potential of molecular imaging with collagen\u2010binding peptides for noninvasive imaging of diffuse cardiac fibrosis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.121.022139","type":"journal-article","created":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T09:53:35Z","timestamp":1631526815000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":27,"title":["Collagen\u2010Targeted Peptides for Molecular Imaging of Diffuse Cardiac Fibrosis"],"prefix":"10.1161","volume":"10","author":[{"given":"Martin","family":"Ezeani","sequence":"first","affiliation":[{"name":"NanoBiotechnology Laboratory Australian Centre for Blood Diseases Central Clinical School Monash University Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asif","family":"Noor","sequence":"additional","affiliation":[{"name":"School of Chemistry Bio21 Molecular Science and Biotechnology Institute University of Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Alt","sequence":"additional","affiliation":[{"name":"NanoTheranostics Laboratory Australian Centre for Blood Diseases Central Clinical School Monash University Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5841-560X","authenticated-orcid":false,"given":"Sean","family":"Lal","sequence":"additional","affiliation":[{"name":"School of Medical Sciences Faculty of Medicine and Health University of Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5373-0080","authenticated-orcid":false,"given":"Paul S.","family":"Donnelly","sequence":"additional","affiliation":[{"name":"School of Chemistry Bio21 Molecular Science and Biotechnology Institute University of Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph E.","family":"Hagemeyer","sequence":"additional","affiliation":[{"name":"NanoBiotechnology Laboratory Australian Centre for Blood Diseases Central Clinical School Monash University Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6714-9131","authenticated-orcid":false,"given":"Be\u2019eri","family":"Niego","sequence":"additional","affiliation":[{"name":"NanoBiotechnology Laboratory Australian Centre for Blood Diseases Central Clinical School Monash University Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000570"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.08.2195"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.306565"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacep.2017.03.002"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.22847"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.86898"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.089409"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCIMAGING.113.001768"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCIMAGING.108.838367"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.10.084"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.312"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2019.02.006"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2012.10.002"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1536\/ihj.37.483"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1536\/ihj.39.753"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2008.07.007"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2005.08.023"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.05750515"},{"key":"e_1_3_2_20_2","first-page":"S1050\u20101738(20)3","article-title":"Molecular imaging of atrial myopathy: towards early af detection and non\u2010invasive disease management","author":"Ezeani M","year":"2020","unstructured":"Ezeani M, Hagemeyer CE, Lal S, Niego B. 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