Claudin-5 levels are reduced in human end-stage cardiomyopathy

Mays, Tessily A.; Binkley, Philip F.; Lesinski, Amanda; Doshi, Amit A.; Quaile, Michael P.; Margulies, Kenneth B.; Janssen, Paul M. L.; Rafael‐Fortney, Jill A.

doi:10.1016/j.yjmcc.2008.04.005

Cited by 29 publications

(27 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, ephrin-B1 interacts specifically with claudin-5, which was found to be downregulated in dystrophic mice models or in human end-stage cardiomyopathy. 22,42 Given our results showing interactions between ephrin-B1 and claudin-5, one might expect similar dysregulation of ephrin-B1 in human cardiomyopathies. In line with this hypothesis, mouse model of DCM associated with claudin-5 downregulation demonstrated similar structural alterations of the lateral membrane as seen in the ephrin-B1 KO mice.…”

mentioning

confidence: 77%

Ephrin-B1 Is a Novel Specific Component of the Lateral Membrane of the Cardiomyocyte and Is Essential for the Stability of Cardiac Tissue Architecture Cohesion

Genet

Guilbeau‐Frugier

Honton

et al. 2012

Circulation Research

View full text Add to dashboard Cite

Rationale: Cardiac tissue cohesion relying on highly ordered cardiomyocytes (CM) interactions is critical because most cardiomyopathies are associated with tissue remodeling and architecture alterations.Objective: Eph/ephrin system constitutes a ubiquitous system coordinating cellular communications which recently emerged as a major regulator in adult organs. We examined if eph/ephrin could participate in cardiac tissue cyto-organization. Methods and Results:We reported the expression of cardiac ephrin-B1 in both endothelial cells and for the first time in CMs where ephrin-B1 localized specifically at the lateral membrane. Ephrin-B1 knock-out (KO) mice progressively developed cardiac tissue disorganization with loss of adult CM rod-shape and sarcomeric and intercalated disk structural disorganization confirmed in CM-specific ephrin-B1 KO mice. CMs lateral membrane exhibited abnormal structure by electron microscopy and notably increased stiffness by atomic force microscopy. In wild-type CMs, ephrin-B1 interacted with claudin-5/ZO-1 complex at the lateral membrane, whereas the complex disappeared in KO/CM-specific ephrin-B1 KO mice. Ephrin-B1 deficiency resulted in decreased mRNA expression of CM basement membrane components and disorganized fibrillar collagen matrix, independently of classical integrin/dystroglycan system. KO/CM-specific ephrin-B1 KO mice exhibited increased left ventricle diameter and delayed atrioventricular conduction. Under pressure overload stress, KO mice were prone to death and exhibited striking tissue disorganization. Finally, failing CMs displayed downregulated ephrin-B1/claudin-5 gene expression linearly related to the ejection fraction. Conclusions:Ephrin-B1 is necessary for cardiac tissue architecture cohesion by stabilizing the adult CM morphology through regulation of its lateral membrane. Because decreased ephrin-B1 is associated with molecular/functional cardiac defects, it could represent a new actor in the transition toward heart failure. (Circ Res. 2012;110:688-700.) Key Words: cardiomyocyte Ⅲ extracellular matrix Ⅲ lateral membrane Ⅲ cardiac tissue Ⅲ architecture Ⅲ heart failure T he heart constitutes a particular compact organ relying on strong tissue architecture cohesion and tight cellular interactions that ensure both mechanical and electrochemical coupling. Thus, most cardiopathies are associated with cardiac tissue remodeling and with alterations in architecture involved in disease progression toward heart failure (HF).Despite considerable advances in the field and development of effective drugs, HF still remains a prevalent condition associated with high morbidity and mortality rates. This could be in part explained by still imperfect knowledge of molecular basis at the origin of HF. In fact, to date, most research has focused on cardiomyocyte (CM) contractile dysfunction Original received December 15, 2011; revision received January 16, 2012; accepted January 25, 2012. In December 2011, the average time from submission to first decision for all original research pape...

show abstract

mentioning

confidence: 77%

Ephrin-B1 Is a Novel Specific Component of the Lateral Membrane of the Cardiomyocyte and Is Essential for the Stability of Cardiac Tissue Architecture Cohesion

Genet

Guilbeau‐Frugier

Honton

et al. 2012

Circulation Research

View full text Add to dashboard Cite

show abstract

“…On the other hand, alterations of a tight junction protein have been reported in human cardiomyopathy samples, and it has been suggested that reduction in claudin-5 may participate in the pathway to end-stage heart failure. [40]…”

Section: Discussionmentioning

confidence: 99%

Cardiac functions assessment in children with celiac disease and its correlation with the degree of mucosal injury: Doppler tissue imaging study

Fathy¹,

Abo‐Haded²,

Al-Ahmadi³

et al. 2016

Saudi J Gastroenterol

View full text Add to dashboard Cite

Background/Aims:Celiac disease (CD)-associated cardiologic disorders is a growing concern. However, data regarding cardiac affection in children with CD are few. This study aimed at assessing the subclinical impact of CD on the global myocardial performance in Saudi children with CD using Doppler tissue imaging (DTI).Patients and Methods:Conventional two-dimensional echocardiography was performed among 20 Saudi children with CDas well as 20 age and sex-matched healthy controls. DTI were used to determine right ventricular (RV) and left ventricular (LV) Tei indexes. These findings were correlated with the Modified Marsh Classification of the histologic findings in CD.Results:LV and RV Tei indexes were significantly higher in children with CD than the control group (mean ± standard deviation: 0.47 ± 0.05 vs. 0.31 ± 0.18; P < 0.0005 and 0.51 ± 0.04 vs. 0.32 ± 0.05; P < 0.0001, respectively). RV Tei index was found to be positively correlated with the Modified Marsh Classification of CD (r = 0.7753, P < 0.0001). LV Tei index tended to be more affected in patients with more severe histologic findings, however, such relation did not reach statistical significance (r = 0.2479, P = 0.292). Fractional shortening did not correlate with the Modified Marsh Classification of histologic findings in CD patients (r= −0.11, P = 0.641).Conclusions:Subclinical myocardial dysfunction of both ventricles occurs in children with CD. The DTI method appears to be more sensitive than conventional two-dimensional echocardiography in the early detection of myocardial dysfunction in children with CD.

show abstract

“…Accordingly, the claudin-mediated sealing and/or molecular remodeling of the lateral region where cardiomyocytes are associated with the basal lamina or extracellular matrix is important for adaptation to mechanical stress. Indeed, changes in the expression of claudin 5 have been reported in the lateral membrane of cardiomyocytes in a dystrophic mouse with dilated cardiomyopathy (47,48).…”

Section: Discussionmentioning

confidence: 99%

Identification of Transcription Factor E3 (TFE3) as a Receptor-independent Activator of Gα16

Sato

Hiraoka

Suzuki

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Receptor-independent G-protein regulators provide diverse mechanisms for signal input to G-protein-based signaling systems, revealing unexpected functional roles for G-proteins. As part of a broader effort to identify disease-specific regulators for heterotrimeric G-proteins, we screened for such proteins in cardiac hypertrophy using a yeast-based functional screen of mammalian cDNAs as a discovery platform. We report the identification of three transcription factors belonging to the same family, transcription factor E3 (TFE3), microphthalmia-associated transcription factor, and transcription factor EB, as novel receptor-independent activators of G-protein signaling selective for G␣ 16 . TFE3 and G␣ 16 were both up-regulated in cardiac hypertrophy initiated by transverse aortic constriction. In protein interaction studies in vitro, TFE3 formed a complex with G␣ 16 but not with G␣ i3 or G␣ s . Although increased expression of TFE3 in heterologous systems had no influence on receptormediated G␣ 16 signaling at the plasma membrane, TFE3 actually translocated G␣ 16 to the nucleus, leading to the induction of claudin 14 expression, a key component of membrane structure in cardiomyocytes. The induction of claudin 14 was dependent on both the accumulation and activation of G␣ 16 by TFE3 in the nucleus. These findings indicate that TFE3 and G␣ 16 are up-regulated under pathologic conditions and are involved in a novel mechanism of transcriptional regulation via the relocalization and activation of G␣ 16 .

show abstract

Claudin-5 levels are reduced in human end-stage cardiomyopathy

Cited by 29 publications

References 32 publications

Ephrin-B1 Is a Novel Specific Component of the Lateral Membrane of the Cardiomyocyte and Is Essential for the Stability of Cardiac Tissue Architecture Cohesion

Ephrin-B1 Is a Novel Specific Component of the Lateral Membrane of the Cardiomyocyte and Is Essential for the Stability of Cardiac Tissue Architecture Cohesion

Cardiac functions assessment in children with celiac disease and its correlation with the degree of mucosal injury: Doppler tissue imaging study

Identification of Transcription Factor E3 (TFE3) as a Receptor-independent Activator of Gα16

Contact Info

Product

Resources

About