High-mobility group box-1 protein induces osteogenic phenotype changes in aortic valve interstitial cells

Wang, Bo; Li, Fēi; Zhang, Chao; Wei, Guangxia; Liao, Pingping; Dong, Nianguo

doi:10.1016/j.jtcvs.2015.09.077

Cited by 30 publications

(31 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Passmore et al [26] demonstrated that osteopontin altered endothelial and VIC behavior in calcific AV stenosis through HMGB1 regulation. Our previous work also suggested that HMGB1 induced high production of pro-inflammatory cytokines and promoted the osteoblastic differentiation and calcification of VICs [7]. In this study, we further supported the role of HMGB1 in CAVD by demonstrating that HMGB1 could also induce myofibroblastic transition of VICs.…”

Section: Discussionsupporting

confidence: 84%

“…We found that the expression of IL-18 and HMGB1 was markedly increased in calcific AVs compared to normal ones (fig. 1a, b, d) [7]. Transition from VICs to myofibroblasts is a critical step in valvular pathology [11].…”

Section: Resultsmentioning

confidence: 99%

“…High mobility group box 1 protein (HMGB1), one of the most important damage-associated molecular patterns, is released from cells following the formation and activation of inflammasome [6]. In our previous study, HMGB1 was demonstrated to promote the osteogenic differentiation and calcification of VICs [7]. However, it is unknown whether IL-18 and HMGB1 contribute to VIC myofibroblastic transition.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Role of High Mobility Group Box 1 Protein in Interleukin-18-Induced Myofibroblastic Transition of Valvular Interstitial Cells

Wang

Wei²,

Liu³

et al. 2016

Cardiology

Self Cite

View full text Add to dashboard Cite

Background: Increased levels of interleukin-18 (IL-18) and high mobility group box 1 protein (HMGB1) have been reported in patients with calcific aortic valve disease (CAVD). However, the role of IL-18 and HMGB1 in the modulation of the valvular interstitial cell (VIC) phenotype remains unclear. We hypothesized that HMGB1 mediates IL-18-induced myofibroblastic transition of VICs. Methods: The expression of IL-18, HMGB1 and α-smooth muscle actin (α-SMA) in human aortic valves was evaluated by immunohistochemical staining, real-time polymerase chain reaction and immunoblotting. Plasma concentrations of IL-18 and HMGB1 were measured using the ELISA kit. Cultured human aortic VICs were used as an in vitro model. Results: Immunohistochemistry and immunoblotting revealed increased levels of IL-18, HMGB1 and α-SMA in calcific valves. Circulating IL-18 and HMGB1 levels were also higher in CAVD patients. In vitro, IL-18 induced upregulation of HMGB1 and α-SMA in VICs. Moreover, IL-18 induced secretion of HMGB1 to the extracellular space and activation of nuclear factor kappa-B (NF-κB). Blockade of NF-κB abrogated the upregulation and release of HMGB1 induced by IL-18. Whereas HMGB1 inhibition attenuated the IL-18-induced expression of α-SMA, HMGB1 enhanced the effect of IL-18. Conclusions: We demonstrated for the first time that both tissue and plasma levels of IL-18 and HMGB1 were increased in patients with CAVD. Mechanically, HMGB1 mediated IL-18-induced VIC myofibroblastic transition.

show abstract

Section: Discussionsupporting

confidence: 84%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Role of High Mobility Group Box 1 Protein in Interleukin-18-Induced Myofibroblastic Transition of Valvular Interstitial Cells

Wang

Wei²,

Liu³

et al. 2016

Cardiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recently, it was demonstrated that HMGB1 can trigger the differentiation of mesenchymal stem cells into osteoblasts, which may provide a theoretical basis for improving clinical treatments for fractures [63, 64]. Wang et al observed that HMGB1 promotes osteoblastic differentiation and calcification of aortic valve interstitial cells (VICs) through TLR4-JNK-NF-κB signaling [65]. …”

Section: Possible Mechanisms By Which Hmgb1 Promotes Cardiovascular Cmentioning

confidence: 99%

Roles of High Mobility Group Box 1 in Cardiovascular Calcification

Chen¹,

Wang²,

Chen³

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Calcific disease of the cardiovascular system, including atherosclerotic calcification, medial calcification in diabetes and calcific aortic valve disease, is an important risk factor for many adverse cardiovascular events such as ischemic cardiac events and subsequent mortality. Although cardiovascular calcification has long been considered to be a passive degenerative occurrence, it is now recognized as an active and highly regulated process that involves osteochondrogenic differentiation, apoptosis and extracellular vesicle release. Nonetheless, despite numerous studies on the pathogenesis of cardiovascular calcification, the underlying mechanisms remain poorly understood. High mobility group box 1 (HMGB1), a nuclear protein bound to chromatin in almost all eukaryotic cells, acts as a damage-associated molecular pattern (DAMP) when released into the extracellular space upon cell activation, injury or death. Moreover, HMGB1 also functions as a bone-active cytokine participating in bone remodeling and ectopic calcification pathogenesis. However, studies on the roles of HMGB1 in promoting cardiovascular calcification are limited to date, and the mechanisms involved are still unclear. In this review, we summarize recent studies investigating the mechanism of cardiovascular calcification and discuss multiple roles of HMGB1 in its development.

show abstract

“…Valves extracted during operation for aortic dissection. 35,37 These valves are perhaps closest to normal as long as the underlying predisposing cause of dissection is presumed not to affect the aortic valve. One problem is to obtain the valves: these are acute patients admitted at any time of the day or night.…”

mentioning

confidence: 99%

Valve Interstitial Cells: The Key to Understanding the Pathophysiology of Heart Valve Calcification

Rutkovskiy

Malashicheva

Sullivan

et al. 2017

JAHA

243

207

View full text Add to dashboard Cite

High-mobility group box-1 protein induces osteogenic phenotype changes in aortic valve interstitial cells

Abstract: The HMGB1 protein may promote osteoblastic differentiation and calcification of VICs, through the TLR4-JNK-NF-κB signaling pathway.

Cited by 30 publications

References 34 publications

The Role of High Mobility Group Box 1 Protein in Interleukin-18-Induced Myofibroblastic Transition of Valvular Interstitial Cells

The Role of High Mobility Group Box 1 Protein in Interleukin-18-Induced Myofibroblastic Transition of Valvular Interstitial Cells

Roles of High Mobility Group Box 1 in Cardiovascular Calcification

Valve Interstitial Cells: The Key to Understanding the Pathophysiology of Heart Valve Calcification

Contact Info

Product

Resources

About