Please use this identifier to cite or link to this item: doi:10.22028/D291-37769
Title: SMAD3 contributes to ascending aortic dilatation independent of transforming growth factor-beta in bicuspid and unicuspid aortic valve disease
Author(s): Balint, Brittany
Federspiel, Jan
Kollmann, Catherine
Teping, Paul
Schwab, Tanja
Schäfers, Hans-Joachim
Language: English
Title: Scientific reports
Volume: 12
Issue: 1
Publisher/Platform: Springer Nature
Year of Publication: 2022
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: We sought to determine whether there are differences in transforming growth factor-beta (TGFß) signaling in aneurysms associated with bicuspid (BAV) and unicuspid (UAV) aortic valves versus normal aortic valves. Ascending aortic aneurysms are frequently associated with BAV and UAV. The mechanisms are not yet clearly defined, but similarities to transforming growth factor-beta TGFß vasculopathies (i.e. Marfan, Loeys-Dietz syndromes) are reported. Non-dilated (ND) and aneurysmal (D) ascending aortic tissue was collected intra-operatively from individuals with a TAV (N = 10ND, 10D), BAV (N = 7ND, 8D) or UAV (N = 7ND, 8D). TGFß signaling and aortic remodeling were assessed through immuno-assays and histological analyses. TGFß1 was increased in BAV/UAV-ND aortas versus TAV (P = 0.02 and 0.04, respectively). Interestingly, TGFß1 increased with dilatation in TAV (P = 0.03) and decreased in BAV/UAV (P = 0.001). In TAV, SMAD2 and SMAD3 phosphorylation (pSMAD2, pSMAD3) increased with dilatation (all P = 0.04) and with TGFß1 concentration (P = 0.04 and 0.03). No relationship between TGFß1 and pSMAD2 or pSMAD3 was observed for BAV/UAV (all P > 0.05). pSMAD3 increased with dilatation in BAV/UAV aortas (P = 0.01), whereas no relationship with pSMAD2 was observed (P = 0.56). Elastin breaks increased with dilatation in all groups (all P < 0.05). In TAV, elastin degradation correlated with TGFß1, pSMAD2 and pSMAD3 (all P < 0.05), whereas in BAV and UAV aortas, elastin degradation correlated only with pSMAD3 (P = 0.0007). TGFß signaling through SMAD2/SMAD3 contributes to aortic remodeling in TAV, whereas TGFß-independent activation of SMAD3 may underlie aneurysm formation in BAV/UAV aortas. Therefore, SMAD3 should be further investigated as a therapeutic target against ascending aortic dilatation in general, and particularly in BAV/UAV patients.
DOI of the first publication: 10.1038/s41598-022-19335-w
Link to this record: urn:nbn:de:bsz:291--ds-377692
hdl:20.500.11880/34165
http://dx.doi.org/10.22028/D291-37769
ISSN: 2045-2322
Date of registration: 2-Nov-2022
Faculty: M - Medizinische Fakultät
Department: M - Chirurgie
Professorship: M - Prof. Dr. Hans Joachim Schäfers
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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