References of "Hulin, Alexia"
     in
Bookmark and Share    
See detailContribution of macrophages to myxomatous valve disease
Hulin, Alexia ULg; Potter, Sarah; Kim, Andrew et al

Poster (2017)

Detailed reference viewed: 9 (0 ULg)
Full Text
Peer Reviewed
See detailLoss of Axin2 results in impaired heart valve maturation and subsequent myxomatous valve disease.
Hulin, Alexia ULg; Moore, Vicky; James, Jeanne M. et al

in Cardiovascular Research (2017), 113(1), 40-51

AIMS: Myxomatous valve disease (MVD) is the most common aetiology of primary mitral regurgitation. Recent studies suggest that defects in heart valve development can lead to heart valve disease in adults ... [more ▼]

AIMS: Myxomatous valve disease (MVD) is the most common aetiology of primary mitral regurgitation. Recent studies suggest that defects in heart valve development can lead to heart valve disease in adults. Wnt/beta-catenin signalling is active during heart valve development and has been reported in human MVD. The consequences of increased Wnt/beta-catenin signalling due to Axin2 deficiency in postnatal valve remodelling and pathogenesis of MVD were determined. METHODS AND RESULTS: To investigate the role of Wnt/beta-catenin signalling, we analysed heart valves from mice deficient in Axin2 (KO), a negative regulator of Wnt/beta-catenin signalling. Axin2 KO mice display enlarged mitral and aortic valves (AoV) after birth with increased Wnt/beta-catenin signalling and cell proliferation, whereas Sox9 expression and collagen deposition are decreased. At 2 months in Axin2 KO mice, the valve extracellular matrix (ECM) is stratified but distal AoV leaflets remain thickened and develop aortic insufficiency. Progressive myxomatous degeneration is apparent at 4 months with extensive ECM remodelling and focal aggrecan-rich areas, along with increased BMP signalling. Infiltration of inflammatory cells is also observed in Axin2 KO AoV prior to ECM remodelling. Overall, these features are consistent with the progression of human MVD. Finally, Axin2 expression is decreased and Wnt/beta-catenin signalling is increased in myxomatous mitral valves in a murine model of Marfan syndrome, supporting the importance of Wnt/beta-catenin signalling in the development of MVD. CONCLUSIONS: Altogether, these data indicate that Axin2 limits Wnt/beta-catenin signalling after birth and allows proper heart valve maturation. Moreover, dysregulation of Wnt/beta-catenin signalling resulting from loss of Axin2 leads to progressive MVD. [less ▲]

Detailed reference viewed: 9 (0 ULg)
See detailLoss of Axin2 leads to Myxomatous Valve Disease
Hulin, Alexia ULg; Yutzey, Katherine

Poster (2016)

Detailed reference viewed: 8 (0 ULg)
See detailLoss of axin2 in murine aortic valves leads to myxomatous disease
Hulin, Alexia ULg; Alfieri, Christina M.; Yutzey, Katherine E.

Poster (2015)

Detailed reference viewed: 6 (0 ULg)
See detailChondrogenic Pathways Involved In The Development of Myxomatous Valve Disease
Hulin, Alexia ULg; Cheek, Jonathan D.; Alfieri, Christina M. et al

Poster (2014)

Detailed reference viewed: 6 (0 ULg)
Full Text
Peer Reviewed
See detailLoss of beta-catenin promotes chondrogenic differentiation of aortic valve interstitial cells.
Fang, Ming; Alfieri, Christina M.; Hulin, Alexia ULg et al

in Arteriosclerosis, thrombosis, and vascular biology (2014), 34(12), 2601-8

OBJECTIVE: The Wnt/beta-catenin signaling pathway has been implicated in human heart valve disease and is required for early heart valve formation in mouse and zebrafish. However, the specific functions ... [more ▼]

OBJECTIVE: The Wnt/beta-catenin signaling pathway has been implicated in human heart valve disease and is required for early heart valve formation in mouse and zebrafish. However, the specific functions of Wnt/beta-catenin signaling activity in heart valve maturation and maintenance in adults have not been determined previously. APPROACH AND RESULTS: Here, we show that Wnt/beta-catenin signaling inhibits Sox9 nuclear localization and proteoglycan expression in cultured chicken embryo aortic valves. Loss of beta-catenin in vivo in mice, using Periostin(Postn)Cre-mediated tissue-restricted loss of beta-catenin (Ctnnb1) in valvular interstitial cells, leads to the formation of aberrant chondrogenic nodules and induction of chondrogenic gene expression in adult aortic valves. These nodular cells strongly express nuclear Sox9 and Sox9 downstream chondrogenic extracellular matrix genes, including Aggrecan, Col2a1, and Col10a1. Excessive chondrogenic proteoglycan accumulation and disruption of stratified extracellular matrix maintenance in the aortic valve leaflets are characteristics of myxomatous valve disease. Both in vitro and in vivo data demonstrate that the loss of Wnt/beta-catenin signaling leads to increased nuclear expression of Sox9 concomitant with induced expression of chondrogenic extracellular matrix proteins. CONCLUSIONS: beta-Catenin limits Sox9 nuclear localization and inhibits chondrogenic differentiation during valve development and in adult aortic valve homeostasis. [less ▲]

Detailed reference viewed: 13 (0 ULg)
Full Text
Peer Reviewed
See detailEmerging pathogenic mechanisms in human myxomatous mitral valve: lessons from past and novel data.
Hulin, Alexia ULg; Deroanne, Christophe ULg; Lambert, Charles ULg et al

in Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology (2013), 22(4), 245-50

INTRODUCTION: Myxomatous mitral valve is one of the most common heart valves diseases in human and has been well characterized at a functional and morphological level. Diseased valves are thickened as a ... [more ▼]

INTRODUCTION: Myxomatous mitral valve is one of the most common heart valves diseases in human and has been well characterized at a functional and morphological level. Diseased valves are thickened as a result of extracellular matrix remodeling and proteoglycans accumulation accompanied by the disruption of the stratified structures of the leaflets. METHODS: Global transcriptomic analysis was used as a start-up to investigate potential pathogenic mechanisms involved in the development of the human idiopathic myxomatous mitral valve, which have been elusive for many years. RESULTS: These prospective analyses have highlighted the potential role of apparently unrelated molecules in myxomatous mitral valve such as members of the transforming growth factor-beta superfamily, aggrecanases of the "a disintegrin and metalloprotease with thrombospondin repeats I" family, and a weakening of the protection against oxidative stress. We have integrated, in this review, recent transcriptomic data from our laboratory [A. Hulin, C.F. Deroanne, C.A. Lambert, B. Dumont, V. Castronovo, J.O. Defraigne, et al. Metallothionein-dependent up-regulation of TGF-beta2 participates in the remodelling of the myxomatous mitral valve. Cardiovasc Res 2012;93:480-489] and from the publication of Sainger et al. [R. Sainger, J.B. Grau, E. Branchetti, P. Poggio, W.F. Seefried, B.C. Field, et al. Human myxomatous mitral valve prolapse: role of bone morphogenetic protein 4 in valvular interstitial cell activation. J Cell Physiol 2012;227:2595-2604] with existing literature and information issued from the study of monogenic syndromes and animal models. CONCLUSION: Understanding cellular alterations and molecular mechanisms involved in myxomatous mitral valve should help at identifying relevant targets for future effective pharmacological therapy to prevent or reduce its progression. [less ▲]

Detailed reference viewed: 13 (0 ULg)
Full Text
Peer Reviewed
See detailTgfbeta-Smad and MAPK signaling mediate scleraxis and proteoglycan expression in heart valves.
Barnette, Damien N.; Hulin, Alexia ULg; Ahmed, A. S. Ishtiaq et al

in Journal of Molecular and Cellular Cardiology (2013), 65

Mature heart valves are complex structures consisting of three highly organized extracellular matrix layers primarily composed of collagens, proteoglycans and elastin. Collectively, these diverse matrix ... [more ▼]

Mature heart valves are complex structures consisting of three highly organized extracellular matrix layers primarily composed of collagens, proteoglycans and elastin. Collectively, these diverse matrix components provide all the necessary biomechanical properties for valve function throughout life. In contrast to healthy valves, myxomatous valve disease is the most common cause of mitral valve prolapse in the human population and is characterized by an abnormal abundance of proteoglycans within the valve tri-laminar structure. Despite the clinical significance, the etiology of this phenotype is not known. Scleraxis (Scx) is a basic-helix-loop-helix transcription factor that we previously showed to be required for establishing heart valve structure during remodeling stages of valvulogenesis. In this study, we report that remodeling heart valves from Scx null mice express decreased levels of proteoglycans, particularly chondroitin sulfate proteoglycans (CSPGs), while overexpression in embryonic avian valve precursor cells and adult porcine valve interstitial cells increases CSPGs. Using these systems we further identify that Scx is positively regulated by canonical Tgfbeta2 signaling during this process and this is attenuated by MAPK activity. Finally, we show that Scx is increased in myxomatous valves from human patients and mouse models, and overexpression in human mitral valve interstitial cells modestly increases proteoglycan expression consistent with myxomatous mitral valve phenotypes. Together, these studies identify an important role for Scx in regulating proteoglycans in embryonic and mature valve cells and suggest that imbalanced regulation could influence myxomatous pathogenesis. [less ▲]

Detailed reference viewed: 12 (0 ULg)