{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T12:16:18Z","timestamp":1784808978859,"version":"3.55.0"},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,11,21]],"date-time":"2019-11-21T00:00:00Z","timestamp":1574294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["EXC62"],"award-info":[{"award-number":["EXC62"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Anatomy"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Heart failure with preserved ejection fraction (HFpEF) is characterized by diastolic dysfunction. This study aimed to analyze whether early HFpEF is already associated with ultrastructural alterations and whether they differ quantitatively among the layers of the left ventricular wall. HFpEF was induced in pigs by deoxy\u2010corticosterone acetate (DOCA) treatment along with a high\u2010salt\/high lipid diet over 3\u00a0months and compared with weight\u2010matched normal pigs (<jats:italic>n<\/jats:italic>\u00a0=\u00a05 each). Samples of the left ventricle were taken and processed for light and electron microscopy. Interstitial fibrosis, subcellular composition of cardiomyocytes and mean cardiomyocyte diameter were evaluated by stereology in subendocardial, midmyocardial and subepicardial regions. DOCA enhanced the mean cardiomyocyte diameter in all locations of the ventricle wall to the same degree. The subcellular composition did not differ between the locations and was not altered by DOCA. The volume fraction of interstitium was smaller in the subendocardium of DOCA group than of control group. Within the interstitium, the volume fraction of collagen fibrils (between cardiomyocytes) was increased in the subendocardial and midmyocardial wall layers of the DOCA group but not in the subepicardial layer. Although the capillary length density and average supply area were not altered in response to DOCA in any of the wall layers, the volume fraction of blood vessels related to the interstitial space was enhanced in the subendocardium of the DOCA group but not in the other wall layers. In conclusion, cardiomyocyte changes due to DOCA were similar in subepicardial, midmyocardial and subendocardial regions but DOCA\u2010induced changes in the interstitium appeared to be more pronounced in the subendocardial ventricular wall layers. This suggests a pivotal role of the subendocardial interstitium in the pathogenesis of HFpEF.<\/jats:p>","DOI":"10.1111\/joa.13117","type":"journal-article","created":{"date-parts":[[2019,11,21]],"date-time":"2019-11-21T08:39:31Z","timestamp":1574325571000},"page":"531-539","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A transmural gradient of myocardial remodeling in early\u2010stage heart failure with preserved ejection fraction in the pig"],"prefix":"10.1111","volume":"236","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7827-4867","authenticated-orcid":false,"given":"Christian","family":"M\u00fchlfeld","sequence":"first","affiliation":[{"name":"Institute of Functional and Applied Anatomy Hannover Medical School Hannover Germany"},{"name":"Cluster of Excellence REBIRTH (From Regenerative Biology to Reconstructive Therapy) Hannover Germany"},{"name":"German Center for Lung Research (DZL) Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH) Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Rajces","sequence":"additional","affiliation":[{"name":"Institute of Functional and Applied Anatomy Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Manninger","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Medicine Medical University of Graz Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Alogna","sequence":"additional","affiliation":[{"name":"Department of Cardiology Charit\u00e9 University Medicine Berlin Germany"},{"name":"Berlin Institute of Health (BIH) Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Christin","family":"Wierich","sequence":"additional","affiliation":[{"name":"Institute of Functional and Applied Anatomy Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Scherr","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Medicine Medical University of Graz Graz Austria"},{"name":"Department of Cardiology Cardiovascular Research Institute Maastricht (CARIM) Maastricht University Medical Center Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiner","family":"Post","sequence":"additional","affiliation":[{"name":"Department of Cardiology Contilia Heart and Vessel Centre St. Marien\u2010Hospital M\u00fclheim M\u00fclheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Schipke","sequence":"additional","affiliation":[{"name":"Institute of Functional and Applied Anatomy Hannover Medical School Hannover Germany"},{"name":"Cluster of Excellence REBIRTH (From Regenerative Biology to Reconstructive Therapy) Hannover Germany"},{"name":"German Center for Lung Research (DZL) Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH) Hannover 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