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- Title
Characterization of the sex-specific pattern of angiogenesis and lymphangiogenesis in aortic stenosis.
- Authors
Matilla Cuenca, Lara; Martín-Núñez, Ernesto; Zubillaga, Mattie Garaikoetxea; Navarro, Adela; Vico, Julieta Anabela; Arrieta, Vanessa; Zubillaga, Amaia; Garcia-Peña, Amaia; Fernández-Celis, Amaya; Gainza, Alicia; Álvarez, Virginia; Sádaba, Rafael; López-Andrés, Natalia; Jover García, Eva
- Abstract
Background: The pathophysiological role of angiogenesis and lymphangiogenesis in aortic stenosis (AS) remains unknown. Valve avascularity is seemly abrogated in AS and neovascularization is wellcorrelated with the disease(1,2). We study sex-related differences in angiogenesis and lymphangiogenesis in aortic valves (AVs) and valve interstitial cells (VICs) from AS patients. Methods: 226 patients recruited (60.6% men) with severe AS undergoing surgical valve replacement. Results: The density of total neovessels was higher in AVs from men versus women's. Small and medium neovessels were more abundant in men's AVs. Male AVs exhibited enhanced CD31 and VE-cadherin expressions. Levels of the pro-angiogenic markers [vascular endothelial growth factor (VEGF)-A, VEGF receptor (VEGFR)1, VEGFR2, insulin-like growth factor-binding protein-2 (IGFBP-2), interleukin (IL)-8, chemerin and fibroblast growth factor (FGF)-7] were increased in men's AVs. Transforming growth factor-β expression was higher in male AVs. Expression of antiangiogenic molecules [thrombospondin (Tsp)-1, endostatin and CD36] was upregulated in male AVs, although the levels of Tsp-2, IL-4, IL-12p70 and chondromodulin-1 were similar between sexes. The number of lymphatic vessels and the expression of the lymphangiogenic markers Lyve-1 and D2-40 was enhanced in men's AV also VEGF-C, VEGF-D and VEGFR3. VICs isolated from men's AVs secreted higher amounts of pro-angiogenic (VEGF-A, VEGFR1, IGFBP-2 and FGF-7) and pro-lymphangiogenic factors (VEGF-C, VEGFD and VEGFR3) than women's without changes in antiangiogenic markers. Conclusions: We show that aberrant angiogenic and lymphangiogenic cues are over-represented in male AVs. VICs are a relevant source of multiple morphogens involved in angiogenesis and lymphangiogenesis likely endowing the AV of men with the predominant calcific AS phenotypes (3,4).
- Subjects
NEOVASCULARIZATION; AORTIC stenosis
- Publication
Artery Research, 2023, Vol 29, Issue 1, pS10
- ISSN
1872-9312
- Publication type
Article
- DOI
10.1007/s44200-022-00028-8