ArticleThe Annals of thoracic surgery2015
Adult aortic valve interstitial cells have greater responses to toll-like receptor 4 stimulation.
Article in The Annals of thoracic surgery, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
5 citing papers in PubMed, 9 citations in OpenAlex.
- Self-eating and Heart: The Emerging Roles of Autophagy in Calcific Aortic Valve Disease.Aging and disease · 2021Review
- Collagen fiber regulation in human pediatric aortic valve development and disease.Scientific reports · 2021Article
- Deregulation of TLR4 signaling pathway characterizes Bicuspid Aortic valve syndrome.Scientific reports · 2019Article
- Toll-Like Receptors, Inflammation, and Calcific Aortic Valve Disease.Frontiers in physiology · 2018Review
- High mobility group box 1 induces calcification of aortic valve interstitial cells via toll-like receptor 4.Molecular medicine reports · 2017Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundAortic valve interstitial cells (AVICs) have been implicated in the pathogenesis of calcific aortic valve disease. Signal transducer and activator of transcription 3 (Stat3) possesses antiinflammatory effects. Given that calcification occurs in adult valves, we hypothesized that AVICs from adult valves more likely undergo a proosteogenic phenotypic change than those from pediatric valves and that may be related to different Stat3 activation in the response of those two age groups to toll-like receptor 4 (TLR4).
methodsAVICs from healthy human aortic valve tissues were treated with TLR4 agonist lipopolysaccharide. Cellular levels of TLR4, intercellular adhesion molecule 1, bone morphogenetic protein 2, and alkaline phosphatase, as well as phosphorylation of p-38 mitogen-activated protein kinase (MAPK), nuclear factor-κβ (NF-κβ), and Stat3, were analyzed.
resultsToll-like receptor 4 protein levels were comparable between adult and pediatric AVICs. Adult cells produce markedly higher levels of the above markers after TLR4 stimulation, which is negatively associated with phosphorylation of Stat3. Inhibition of Stat3 enhanced p-38 MAPK and NF-κβ phosphorylation and exaggerated the expression of the above markers in pediatric AVICs after TLR4 stimulation.
conclusionsAdult AVICs exhibit greater inflammatory and osteogenic responses to TLR4 stimulation. The enhanced responses in adult AVICs are at least partly due to lower levels of Stat3 activation in response to TLR4 stimulation relative to pediatric cells. Stat3 functions as a negative regulator of the TLR4 responses in human AVICs. The results suggest that Stat3 activation (tyrosine phosphorylation) may be protective and that TLR4 inhibition could be targeted pharmacologically to treat calcific aortic valve disease.
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