{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:38:33Z","timestamp":1787499513026,"version":"build-2736575974"},"reference-count":80,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,3,21]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Interstitial and perivascular fibrosis may contribute to diabetes\u2010associated heart failure. Pericytes can convert to fibroblasts under conditions of stress and have been implicated in the pathogenesis of fibrotic diseases. We hypothesized that in diabetic hearts, pericytes may convert to fibroblasts, contributing to fibrosis and to the development of diastolic dysfunction.<\/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\">\n                      Using pericyte:fibroblast dual reporter (NG2\n                      <jats:sup>Dsred<\/jats:sup>\n                      [neuron\u2010glial antigen 2 red fluorescent protein variant]; PDGFR\u03b1\n                      <jats:sup>EGFP<\/jats:sup>\n                      [platelet\u2010derived growth factor receptor alpha enhanced green fluorescent protein]) mice in a type 2 diabetic db\/db background, we found that diabetes does not significantly affect pericyte density but reduces the myocardial pericyte:fibroblast ratio. Lineage tracing using the inducible NG2\n                      <jats:sup>CreER<\/jats:sup>\n                      driver, along with reliable labeling of fibroblasts with the PDGFR\u03b1 reporter system, showed no significant pericyte to fibroblast conversion in lean and db\/db hearts. In addition, db\/db mouse cardiac fibroblasts did not undergo myofibroblast conversion and had no significant induction of structural collagens but exhibited a matrix\u2010preserving phenotype, associated with increased expression of antiproteases, matricellular genes, matrix cross\u2010linking enzymes, and the fibrogenic transcription factor\n                      <jats:italic>cMyc<\/jats:italic>\n                      . In contrast, db\/db mouse cardiac pericytes had increased expression of\n                      <jats:italic>Timp3<\/jats:italic>\n                      , without any changes in expression of other fibrosis\u2010associated genes. The matrix\u2010preserving phenotype of diabetic fibroblasts was associated with induction of genes encoding oxidative (\n                      <jats:italic>Ptgs2<\/jats:italic>\n                      \/cycloxygenase\u20102, and\n                      <jats:italic>Fmo2<\/jats:italic>\n                      ) and antioxidant proteins (\n                      <jats:italic>Hmox1<\/jats:italic>\n                      ,\n                      <jats:italic>Sod1<\/jats:italic>\n                      ). In vitro, high glucose partially recapitulated the in vivo changes in diabetic fibroblasts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Diabetic fibrosis is not mediated through pericyte to fibroblast conversion but involves acquisition of a matrix\u2010preserving fibroblast program, which is independent of myofibroblast conversion and is only partially explained by the effects of the hyperglycemic environment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.122.027463","type":"journal-article","created":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T06:42:51Z","timestamp":1678344171000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":21,"title":["Diabetes Induces Cardiac Fibroblast Activation, Promoting a Matrix\u2010Preserving Nonmyofibroblast Phenotype, Without Stimulating Pericyte to Fibroblast Conversion"],"prefix":"10.1161","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4386-7128","authenticated-orcid":false,"given":"Linda","family":"Alex","sequence":"first","affiliation":[{"name":"The Wilf Family Cardiovascular Research Institute Department of Medicine (Cardiology), Albert Einstein College of Medicine Bronx NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8482-591X","authenticated-orcid":false,"given":"Izabela","family":"Tuleta","sequence":"additional","affiliation":[{"name":"The Wilf Family Cardiovascular Research Institute Department of Medicine (Cardiology), Albert Einstein College of Medicine Bronx NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5212-3403","authenticated-orcid":false,"given":"Anis","family":"Hanna","sequence":"additional","affiliation":[{"name":"The Wilf Family Cardiovascular Research Institute Department of Medicine (Cardiology), Albert Einstein College of Medicine Bronx NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8186-5131","authenticated-orcid":false,"given":"Nikolaos G.","family":"Frangogiannis","sequence":"additional","affiliation":[{"name":"The Wilf Family Cardiovascular Research Institute Department of Medicine (Cardiology), Albert Einstein College of Medicine Bronx NY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61402-1"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(74)90089-7"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.11.033"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehn153"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2018.02.026"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60987-8"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(72)90595-4"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcad.2019.03.003"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.315913"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.11.019"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.311586"},{"key":"e_1_3_1_13_2","article-title":"Cellular interplay between cardiomyocytes and non\u2010myocytes in diabetic cardiomyopathy","author":"Phang RJ","unstructured":"Phang RJ, Ritchie RH, Hausenloy DJ, Lees JG, Lim SY. 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