1. Characterization of the sex-specific pattern of angiogenesis and lymphangiogenesis in aortic stenosis.
- Author
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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, and Jover García, Eva
- Subjects
NEOVASCULARIZATION ,AORTIC stenosis - 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). [ABSTRACT FROM AUTHOR]
- Published
- 2023
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