{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T14:40:51Z","timestamp":1784644851910,"version":"3.55.0"},"reference-count":99,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T00:00:00Z","timestamp":1631059200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01EO1302"],"award-info":[{"award-number":["01EO1302"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Immunosuppressants are a mandatory therapy for transplant patients to avoid rejection of the transplanted organ by the immune system. However, there are several known side effects, including alterations of the vasculature, which involve a higher occurrence of cardiovascular events. While the effects of the commonly applied immunosuppressive drugs cyclosporine A (CsA) and tacrolimus (Tac) on mature endothelial cells have been addressed in several studies, we focused our research on the unexplored effects of CsA and Tac on endothelial colony-forming cells (ECFCs), a subgroup of endothelial progenitor cells, which play an important role in vascular repair and angiogenesis. We hypothesized that CsA and Tac induce functional defects and activate an inflammatory cascade via NF-\u03baB signaling in ECFCs. ECFCs were incubated with different doses (0.01 \u00b5M\u201310 \u00b5M) of CsA or Tac. ECFC function was determined using in vitro models. The expression of inflammatory cytokines and adhesion molecules was explored by quantitative real-time PCR and flow cytometry. NF-\u03baB subunit modification was assessed by immunoblot and immunofluorescence. CsA and Tac significantly impaired ECFC function, including proliferation, migration, and tube formation. TNF-\u03b1, IL-6, VCAM, and ICAM mRNA expression, as well as PECAM and VCAM surface expression, were enhanced. Furthermore, CsA and Tac led to NF-\u03baB p65 subunit phosphorylation and nuclear translocation. Pharmacological inhibition of NF-\u03baB by parthenolide diminished CsA- and Tac-mediated proinflammatory effects. The data of functional impairment and activation of inflammatory signals provide new insight into mechanisms associated with CsA and Tac and cardiovascular risk in transplant patients.<\/jats:p>","DOI":"10.3390\/ijms22189696","type":"journal-article","created":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T02:41:07Z","timestamp":1631068867000},"page":"9696","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Cyclosporine A and Tacrolimus Induce Functional Impairment and Inflammatory Reactions in Endothelial Progenitor Cells"],"prefix":"10.3390","volume":"22","author":[{"given":"Nadia","family":"Meyer","sequence":"first","affiliation":[{"name":"Gynecology Research Unit, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Brodowski","sequence":"additional","affiliation":[{"name":"Gynecology Research Unit, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany"},{"name":"Department of Obstetrics and Gynecology, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantin","family":"von Kaisenberg","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5996-2373","authenticated-orcid":false,"given":"Bianca","family":"Schr\u00f6der-Heurich","sequence":"additional","affiliation":[{"name":"Gynecology Research Unit, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1924-5695","authenticated-orcid":false,"given":"Frauke","family":"von Versen-H\u00f6ynck","sequence":"additional","affiliation":[{"name":"Gynecology Research Unit, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany"},{"name":"Department of Obstetrics and Gynecology, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Waller, D.G., and Sampson, A.P. 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