Bone regulatory factors NFATc1 and Osterix in human calcific aortic valves

Alexopoulos, A.H.; Bravou, Vasiliki; Peroukides, Stavros; Kaklamanis, Loukas; Varakis, John; Alexopoulos, Dimitrios; Papadaki, Helen

doi:10.1016/j.ijcard.2008.10.014

Cited by 61 publications

(57 citation statements)

References 45 publications

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“…High incidence of the B allele has been found in aortic stenosis and is related with reduced calcium absorption, bone resorption and increased expression of parathormone [3,13]. Runx2, also designated Cbfa1, belongs to the Runt domain family and is the master transcription factor for bone formation inducing transcription of osteoblast-related genes that enhance mineralization such as osteocalcin gene [24]. Trancriptional activity of Runx2 may be suppresed by Notch1 signaling.…”

Section: Bone Metabolismmentioning

confidence: 99%

“…6) [3,24]. Sox9, a critical regulator of both early and late stages of chondrogenesis, is overexpressed in stenotic aortic valves [24]. Several lines of evidence suggest an important role of the OPG (osteoprotegerin)/RANKL (receptor activator of nuclear factor NF-κB ligand)/RANK (receptor activator of nuclear factor NF-κB) axis in valve pathology [28,29].…”

Section: Bone Factorsmentioning

confidence: 99%

“…Angiogenesis may be implicated in calcification process by various ways including recruitment of inflammatory cells, transdifferentiation of pericytes of neovessel wall and secretion of cytokines from activated endothelial cells [24]. The whole process is related with increased levels of endothelial nitric oxide synthase, SPARC protein (secreted protein, acidic and rich in cysteine/osteonectin), VEGF and its receptors Flt-1 and Flk-1 [13].…”

Section: Neoangiosismentioning

confidence: 99%

“…In addition, recent research has shown that aortic VICs in areas containing calcific deposits showed significantly higher Osterix and NFATc1 nuclear immunolocalization compared to non-calcified fibrocellular regions. NFATc1 is a member of a multigene family of transcription factors that belong to the Rel group and control T lymphocyte activation and differentiation [24]. Therefore, inflammation and osteogenesis are indissolubly related.…”

Section: Inflammationmentioning

confidence: 99%

See 3 more Smart Citations

Pathophysiologic Mechanisms of Age – Related Aortic Valve Calcification

Alexopoulos¹,

Michelakakis²,

Papadaki³

2011

Aortic Stenosis - Etiology, Pathophysiology and Treatment

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Section: Bone Metabolismmentioning

confidence: 99%

Section: Bone Factorsmentioning

confidence: 99%

Section: Neoangiosismentioning

confidence: 99%

Section: Inflammationmentioning

confidence: 99%

See 2 more Smart Citations

Pathophysiologic Mechanisms of Age – Related Aortic Valve Calcification

Alexopoulos¹,

Michelakakis²,

Papadaki³

2011

Aortic Stenosis - Etiology, Pathophysiology and Treatment

Self Cite

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“…These cells can differentiate into osteoblast-like cells and thus contribute to valvular calcification (10,11). However, we previously observed that stimulation of Toll-like receptor (TLR) 2 or 4 in human AVICs induces osteogenic responses (12,13).…”

mentioning

confidence: 99%

IL-37 Suppresses MyD88-mediated Inflammatory Responses in Human Aortic Valve Interstitial Cells

Zhan¹,

Zeng²,

Song³

et al. 2017

Mol Med

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Calcific aortic valve disease (CAVD) is common among the elderly, and aortic valve interstitial cells (AVICs) exhibit unique inflammatory and osteogenic responses to proinflammatory stimulation, which plays an important role in valvular fibrosis and calcification. Thus, suppression of AVIC proinflammatory response may have therapeutic utility for the prevention of CAVD progression. Interleukin (IL)-37, an antiinflammatory cytokine, reduces tissue inflammation. This study aimed to test the hypothesis that IL-37 suppresses human AVIC inflammatory responses to Toll-like receptor (TLR) agonists. Human AVICs were exposed to Pam3CSK4, poly(I:C) and lipopolysaccharide in the presence and absence of recombinant human IL-37. Stimulation of TLR4 increased the production of intercellular adhesion molecule-1, IL-6, IL-8 and monocyte chemoattractant protein-1. Knockdown of myeloid differentiation factor 88 (MyD88) or TIR-domain-containing adaptor-inducing interferon-β differentially affected inflammatory mediator production following TLR4 stimulation. IL-37 reduced production of these inflammatory mediators induced by TLR4. Moreover, knockdown of IL-37 enhanced induction of these mediators by TLR4. IL-37 also suppressed inflammatory mediator production induced by the MyD88-dependent TLR2, but had no effect on the inflammatory responses to the TRIF-dependent TLR3. Furthermore, IL-37 inhibited NF-κB activation induced by TLR2 or TLR4 through a mechanism dependent of IL-18 receptor α-chain. Activation of TLR2, TLR3 or TLR4 upregulates the production of inflammatory mediators in human AVICs. IL-37 suppresses MyD88-mediated responses to reduce inflammatory mediator production following stimulation of TLR2 and TLR4. This antiinflammatory cytokine may be useful for suppression of aortic valve inflammation elicited by MyD88-dependent TLR signaling.

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Pathophysiology of Aortic Stenosis and Mitral Regurgitation

Perrucci

Zanobini

Gripari

et al. 2017

Comprehensive Physiology

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The global impact of the spectrum of valve diseases is a crucial, fast-growing, and underrecognized health problem. The most prevalent valve diseases, requiring surgical intervention, are represented by calcific and degenerative processes occurring in heart valves, in particular, aortic and mitral valve. Due to the increasing elderly population, these pathologies will gain weight in the global health burden. The two most common valve diseases are aortic valve stenosis (AVS) and mitral valve regurgitation (MR). AVS is the most commonly encountered valve disease nowadays and affects almost 5% of elderly population. In particular, AVS poses a great challenge due to the multiple comorbidities and frailty of this patient subset. MR is also a common valve pathology and has an estimated prevalence of 3% in the general population, affecting more than 176 million people worldwide. This review will focus on pathophysiological changes in both these valve diseases, starting from the description of the anatomical aspects of normal valve, highlighting all the main cellular and molecular features involved in the pathological progression and cardiac consequences. This review also evaluates the main approaches in clinical management of these valve diseases, taking into account of the main published clinical guidelines. © 2017 American Physiological Society. Compr Physiol 7:799-818, 2017.

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Bone regulatory factors NFATc1 and Osterix in human calcific aortic valves

Cited by 61 publications

References 45 publications

Pathophysiologic Mechanisms of Age – Related Aortic Valve Calcification

Pathophysiologic Mechanisms of Age – Related Aortic Valve Calcification

IL-37 Suppresses MyD88-mediated Inflammatory Responses in Human Aortic Valve Interstitial Cells

Pathophysiology of Aortic Stenosis and Mitral Regurgitation

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