{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:27:53Z","timestamp":1772252873001,"version":"3.50.1"},"reference-count":21,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,11,29]],"date-time":"2019-11-29T00:00:00Z","timestamp":1574985600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and objectives: Ischemic and idiopathic heart failure are characterized by reactive cardiac fibrosis and impaired vasculogenesis involving pro-angiogenic factors such as angiogenin, angiopoietin-1 (Ang-1), and angiopoietin-2 (Ang-2), as demonstrated in experimental models of heart failure. However, differences in the molecular pathways between these cardiomyopathies are still unclear. In this short communication, we evaluate and compare the expression of pro-angiogenic molecules in the heart tissue of patients with advanced chronic heart failure (CHF) of ischemic vs. nonischemic etiology. Materials and Methods: We obtained heart tissue at transplantation from left ventricular walls of 16 explanted native hearts affected by either ischemic (ICM) or nonischemic dilated cardiomyopathy (NIDCM). Tissue samples were examined using immunohistochemistry for angiogenic molecules. Results: We found immunopositivity (I-pos) for angiopoietin-1 mainly in the cardiomyocytes, while we observed I-pos for Ang-2 and Tie-2 receptor mainly in endothelial cells. Expression of Procollagen-I (PICP), angiogenin, Ang-1, and Tie-2 receptor was similar in ICM and NIDCM. In contrast, endothelial immunopositivity for Ang-2 was higher in ICM samples than NIDCM (p = 0.03). Conclusions: In our series of CHF heart samples, distribution of Ang-1 and angiogenin was higher in cardiomyocytes while that of Ang-2 was higher in endothelial cells; moreover, Ang-2 expression was higher in ICS than NIDCM. Despite the small series examined, these findings suggest different patterns of angiogenic stimulation in ICM and NIDCM, or at least a more altered endothelial integrity in ICD. Our data may contribute to a better understanding of the angiogenesis signaling pathways in CHF. Further studies should investigate differences in the biochemical processes leading to heart failure.<\/jats:p>","DOI":"10.3390\/medicina55120766","type":"journal-article","created":{"date-parts":[[2019,11,29]],"date-time":"2019-11-29T10:58:21Z","timestamp":1575025101000},"page":"766","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Indexes of Angiogenic Activation in Myocardial Samples of Patients with Advanced Chronic Heart Failure"],"prefix":"10.3390","volume":"55","author":[{"given":"Klara","family":"Komici","sequence":"first","affiliation":[{"name":"Department of Medicine and Health Sciences, University of Molise, 86100 Campobasso, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabella","family":"Gnemmi","sequence":"additional","affiliation":[{"name":"Pulmonary Rehabilitation Unit and Laboratory of Cytoimmunopathology of the Heart and Lung, Istituti Clinici Scientifici Maugeri, 28010 Veruno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Sangiorgi","sequence":"additional","affiliation":[{"name":"Pulmonary Rehabilitation Unit and Laboratory of Cytoimmunopathology of the Heart and Lung, Istituti Clinici Scientifici Maugeri, 28010 Veruno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabio Luigi Massimo","family":"Ricciardolo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Torino, San Luigi Hospital, 10043 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mauro","family":"Rinaldi","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Thoracic Surgery, University of Turin, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3479-0875","authenticated-orcid":false,"given":"Antonino","family":"Di Stefano","sequence":"additional","affiliation":[{"name":"Pulmonary Rehabilitation Unit and Laboratory of Cytoimmunopathology of the Heart and Lung, Istituti Clinici Scientifici Maugeri, 28010 Veruno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ermanno","family":"Eleuteri","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Istituti Clinici Scientifici Maugeri, 28010 Veruno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1038\/nrcardio.2009.130","article-title":"Vascular dysfunction in idiopathic dilated cardiomyopathy","volume":"6","author":"Roura","year":"2009","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"65","DOI":"10.3389\/fcvm.2017.00065","article-title":"Angiogenesis, Cancer, and Vascular Aging","volume":"4","author":"Moryja","year":"2017","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1042\/CS20160129","article-title":"Angiopoietin-Tie signalling in the cardiovascular and lymphatic systems","volume":"131","author":"Eklund","year":"2017","journal-title":"Clin. Sci. (Lond.)"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/S0195-668X(02)00635-8","article-title":"Angiogenesis: Basic pathophysiology and implications for disease","volume":"24","author":"Felmeden","year":"2003","journal-title":"Eur. Heart J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"904","DOI":"10.3389\/fphar.2018.00904","article-title":"New Insights in Cardiac \u03b2-Adrenergic Signaling During Heart Failure and Aging","volume":"9","author":"Eguchi","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1161\/CIRCHEARTFAILURE.113.000329","article-title":"Vascular endothelial growth factor blockade prevents the beneficial effects of \u03b2-blocker therapy on cardiac function, angiogenesis, and remodeling in heart failure","volume":"6","author":"Rengo","year":"2013","journal-title":"Circ. Heart Fail."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s00395-008-0761-9","article-title":"Oxidative stress induces myeloperoxidase expression in endocardial endothelial cells from patients with chronic heart failure","volume":"104","author":"Eleuteri","year":"2009","journal-title":"Basic Res. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1016\/S0002-9149(02)02848-5","article-title":"Vascular endothelial growth factor and soluble P-selectin in acute and chronic congestive heart failure","volume":"90","author":"Chin","year":"2002","journal-title":"Am. J Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.jacc.2003.08.042","article-title":"Plasma angiopoietin-1, angiopoietin-2, and angiopoietin receptor tie-2 levels in congestive heart failure","volume":"43","author":"Chong","year":"2004","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1080\/07853890802001419","article-title":"Elevated angiogenin levels in chronic heart failure","volume":"40","author":"Patel","year":"2008","journal-title":"Ann. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.ejheart.2004.09.011","article-title":"Serum markers of angiogenesis and myocardial ultrasonic tissue characterization in patients with dilated cardiomyopathy","volume":"7","author":"Ohtsuka","year":"2005","journal-title":"Eur. J. Heart Fail."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1161\/CIRCRESAHA.109.196154","article-title":"Angiopoietin-2 confers Atheroprotection in apoE-\/- mice by inhibiting LDL oxidation via nitric oxide","volume":"104","author":"Ahmed","year":"2009","journal-title":"Circ. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.atherosclerosis.2015.05.018","article-title":"Angiopoietin-2 blocking antibodies reduce early atherosclerotic plaque development in mice","volume":"241","author":"Theelen","year":"2015","journal-title":"Atherosclerosis"},{"key":"ref_14","first-page":"1787","article-title":"ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The task force for the diagnosis and treatment of acute and chronic heart failure 2012 of the european society of cardiology. Developed in collaboration with the heart failure association (HFA) of the ESC","volume":"14","author":"McMurray","year":"2012","journal-title":"Eur. Heart J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1177\/1741826710389410","article-title":"Stepwise increase of angiopoietin-2 serum levels is related to haemodynamic and functional impairment in stable chronic heart failure","volume":"18","author":"Eleuteri","year":"2011","journal-title":"Eur. J. Cardiovasc. Prev. Rehabil."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3006","DOI":"10.1093\/eurheartj\/ehm488","article-title":"Plasma angiogenin levels in acute coronary syndromes: Implications for prognosis","volume":"28","author":"Patel","year":"2007","journal-title":"Eur. Heart J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.ijcard.2016.03.005","article-title":"Prognostic value of angiopoietin-2 in patients with chronic heart failure","volume":"212","author":"Eleuteri","year":"2016","journal-title":"Int. J. Cardiol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Lukasz, A., Beutel, G., K\u00fcmpers, P., Denecke, A., Westhoff-Bleck, M., Schieffer, B., Bauersachs, J., Kielstein, J.T., and Tutarel, O. (2013). Angiopoietin-2 in adults with congenital heart disease and heart failure. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0066861"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4552","DOI":"10.1038\/ncomms5552","article-title":"Myocardium-derived angiopoietin-1 is essential for coronary vein formation in the developing heart","volume":"5","author":"Arita","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"432","DOI":"10.7555\/JBR.26.20120006","article-title":"Overexpression of angiopoietin-1 reduces doxorubicin-induced apoptosis in cardiomyocytes","volume":"26","author":"Ren","year":"2012","journal-title":"J. Biomed. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1161\/01.RES.86.9.952","article-title":"Angiopoietin-1 induces endothelial cell sprouting through the activation of focal adhesion kinase and plasmin secretion","volume":"86","author":"Kim","year":"2000","journal-title":"Circ. Res."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/55\/12\/766\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:38:48Z","timestamp":1760189928000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/55\/12\/766"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,29]]},"references-count":21,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["medicina55120766"],"URL":"https:\/\/doi.org\/10.3390\/medicina55120766","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints201910.0077.v1","asserted-by":"object"}]},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,29]]}}}