Lipopolysaccharide Stimulation of Human Aortic Valve Interstitial Cells Activates Inflammation and Osteogenesis

Babu, Ashok; Meng, Xianzhong; Zou, Ning; Yang, Xiao‐Ping; Wang, Maorong; Song, Yong; Cleveland, Joseph C.; Weyant, Michael J.; Banerjee, Anirban; Fullerton, David A.

doi:10.1016/j.athoracsur.2008.03.008

Cited by 55 publications

(52 citation statements)

References 22 publications

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“…These cells constitutively express cytokines such IL-6 and IL-8, as described [30], and also chemokines such as Gro, IL-8, MCP-1, and RANTES, and molecules involved in osteogenesis regulation, like OPG, TIMP1 and 2. Consistent with TLR-signalling data, TLR4 engagement, but not TLR2, promoted the expression of several chemokines, i.e., strong induction of IL-8, as described [30], and also Gro and Groα, and a lower induction of MCP-1, and cytokines such as VEGF and OPG, known to be involved in osteogenesis regulation [2]. Strikingly, TLR3 activation promotes a similar cytokine profile, even induced the expression of more cytokines than LPS, i.e., chemokines such as RANTES, GCP-2, and MIP-3α, and the cytokine IGFBP2.…”

Section: Discussionmentioning

confidence: 99%

Viral and bacterial patterns induce TLR-mediated sustained inflammation and calcification in aortic valve interstitial cells

López¹,

Fernández‐Pisonero

Dueñas

et al. 2012

International Journal of Cardiology

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Section: Discussionmentioning

confidence: 99%

Viral and bacterial patterns induce TLR-mediated sustained inflammation and calcification in aortic valve interstitial cells

López¹,

Fernández‐Pisonero

Dueñas

et al. 2012

International Journal of Cardiology

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“…Work from our laboratory has previously shown that when stimulated by mechanisms of inflammation acting through TLR4, adult AVICS demonstrate increased expression of proinflammatory genes and proteins [18]. In turn, we have also previously shown that such an inflammatory response is linked to mechanisms of osteogenesis [2, 3]; mechanisms of inflammation have been demonstrated to incite mechanisms of osteogenesis in human adult AVICs. Here, we present the similar finding that stimulation of TLR4 in human adult AVICs also induced the expression of proinflammatory and proosteogenic factors.…”

Section: Commentmentioning

confidence: 90%

Adult Aortic Valve Interstitial Cells Have Greater Responses to Toll-Like Receptor 4 Stimulation

Deng

Meng

Zeng

et al. 2015

The Annals of Thoracic Surgery

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Background Aortic 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). Methods AVICs 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. Results Toll-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 N-κβ phosphorylation and exaggerated the expression of the above markers in pediatric AVICs after TLR4 stimulation. Conclusions Adult 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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“…19 Moreover, studies indicate that TLRs may play a significant role in atherosclerosis. 20 Different molecules have been shown to stimulate TLRs including ox-LDL.…”

Section: Toll-like Receptors and Aortic Stenosismentioning

confidence: 99%

Increased Biglycan in Aortic Valve Stenosis Leads to the Overexpression of Phospholipid Transfer Protein via Toll-Like Receptor 2

Derbali

Bossé

Côté

et al. 2010

The American Journal of Pathology

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Aortic stenosis (AS) is the most common valvular heart disease, and it is suspected that atherosclerotic mechanisms are involved in the development of this disorder. Therefore, the retention of lipids within the aortic valve may play a role in the pathobiology of AS. In this study, a gene expression microarray experiment was conducted on human aortic valves with and without AS. The expression levels of transcripts encoding proteoglycans and enzymes involved in lipid retention were compared between the two groups. The microarray results were subsequently replicated in a cohort of 87 AS valves and 36 control valves. In addition, the interaction between proteoglycan and lipid-modifying enzyme was documented in isolated valve interstitial cells (VICs). The microarray results indicated that only biglycan (BGN) and phospholipid transfer protein (PLTP) were overexpressed in the AS valves. These results were then confirmed by quantitative PCR. The immunohistochemical analysis revealed a colocalization of BGN, PLTP, and Toll-like receptor-2 (TLR 2) in AS valves. In vitro, we showed that BGN induces the production of PLTP in VICs via the stimulation of TLR 2. Thus , increased accumulation of BGN in AS valves contributes to the production of PLTP via TLR 2. These results suggest that intricate links between valve matrix proteins , inflammation , and lipid retention are involved in the pathobiology

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Lipopolysaccharide Stimulation of Human Aortic Valve Interstitial Cells Activates Inflammation and Osteogenesis

Cited by 55 publications

References 22 publications

Viral and bacterial patterns induce TLR-mediated sustained inflammation and calcification in aortic valve interstitial cells

Viral and bacterial patterns induce TLR-mediated sustained inflammation and calcification in aortic valve interstitial cells

Adult Aortic Valve Interstitial Cells Have Greater Responses to Toll-Like Receptor 4 Stimulation

Increased Biglycan in Aortic Valve Stenosis Leads to the Overexpression of Phospholipid Transfer Protein via Toll-Like Receptor 2

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