ArticleAmerican journal of physiology. Heart and circulatory physiology2014
Aortic valve sclerosis in mice deficient in endothelial nitric oxide synthase.
Article in American journal of physiology. Heart and circulatory physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 57 citations in OpenAlex.
- Deciphering the Enigma of Calcific Aortic Valve Disease: The Pivotal Role of Animal Models in Unraveling Pathogenesis and Advancing Therapeutic Strategies.Biomedicines · 2025Review
- Plasma-Derived Extracellular Vesicle-Propagated microRNA From Aortic Stenosis Patients Render Pro-Calcifying Effects on Valve Interstitial Cells.JACC. Basic to translational science · 2025Article
- Nutraceutical COMP-4 confers protection against endothelial dysfunction through the eNOS/iNOS-NO-cGMP pathway.PloS one · 2025Article
- The role of microRNAs in calcific aortic valve disease.Frontiers in cardiovascular medicine · 2025Review
- Diabetes and calcific aortic valve disease: implications of glucose-lowering medication as potential therapy.Frontiers in pharmacology · 2025Review
- Identification of congenital aortic valve malformations in juvenile natriuretic peptide receptor 2-deficient mice using high-frequency ultrasound.American journal of physiology. Heart and circulatory physiology · 2024Article
- Insulin and Insulin-Like Growth Factor 1 Signaling Preserves Sarcomere Integrity in the Adult Heart.Molecular and cellular biology · 2022Article
- Implication of Lipids in Calcified Aortic Valve Pathogenesis: Why Did Statins Fail?Journal of clinical medicine · 2022Review
- Role of oxidative stress in calcific aortic valve disease and its therapeutic implications.Cardiovascular research · 2022Review
- Calcific aortic valve disease: from molecular and cellular mechanisms to medical therapy.European heart journal · 2022Article
- Genetic and Developmental Contributors to Aortic Stenosis.Circulation research · 2021Review
- Inflammatory and Biomechanical Drivers of Endothelial-Interstitial Interactions in Calcific Aortic Valve Disease.Circulation research · 2021Review
- Optical coherence tomography and multiphoton microscopy offer new options for the quantification of fibrotic aortic valve disease in ApoEScientific reports · 2021Article
- Collagen networks within 3D PEG hydrogels support valvular interstitial cell matrix mineralization.Acta biomaterialia · 2021Article
- Article
- AMPK: Potential Therapeutic Target for Vascular Calcification.Frontiers in cardiovascular medicine · 2021Review
- NOTCH Signaling in Aortic Valve Development and Calcific Aortic Valve Disease.Frontiers in cardiovascular medicine · 2021Review
- Aortic Valve Stenosis and Mitochondrial Dysfunctions: Clinical and Molecular Perspectives.International journal of molecular sciences · 2020Review
- NFκB (Nuclear Factor κ-Light-Chain Enhancer of Activated B Cells) Activity Regulates Cell-Type-Specific and Context-Specific Susceptibility to Calcification in the Aortic Valve.Arteriosclerosis, thrombosis, and vascular biology · 2020Article
- Say NO to ROS: Their Roles in Embryonic Heart Development and Pathogenesis of Congenital Heart Defects in Maternal Diabetes.Antioxidants (Basel, Switzerland) · 2019Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Risk factors for fibrocalcific aortic valve disease (FCAVD) are associated with systemic decreases in bioavailability of endothelium-derived nitric oxide (EDNO). In patients with bicuspid aortic valve (BAV), vascular expression of endothelial nitric oxide synthase (eNOS) is decreased, and eNOS(-/-) mice have increased prevalence of BAV. The goal of this study was to test the hypotheses that EDNO attenuates profibrotic actions of valve interstitial cells (VICs) in vitro and that EDNO deficiency accelerates development of FCAVD in vivo. As a result of the study, coculture of VICs with aortic valve endothelial cells (vlvECs) significantly decreased VIC activation, a critical early phase of FCAVD. Inhibition of VIC activation by vlvECs was attenuated by N(G)-nitro-l-arginine methyl ester or indomethacin. Coculture with vlvECs attenuated VIC expression of matrix metalloproteinase-9, which depended on stiffness of the culture matrix. Coculture with vlvECs preferentially inhibited collagen-3, compared with collagen-1, gene expression. BAV occurred in 30% of eNOS(-/-) mice. At age 6 mo, collagen was increased in both bicuspid and trileaflet eNOS(-/-) aortic valves, compared with wild-type valves. At 18 mo, total collagen was similar in eNOS(-/-) and wild-type mice, but collagen-3 was preferentially increased in eNOS(-/-) mice. Calcification and apoptosis were significantly increased in BAV of eNOS(-/-) mice at ages 6 and 18 mo. Remarkably, these histological changes were not accompanied by physiologically significant valve stenosis or regurgitation. In conclusion, coculture with vlvECs inhibits specific profibrotic VIC processes. In vivo, eNOS deficiency produces fibrosis in both trileaflet and BAVs but produces calcification only in BAVs.
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