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Netherlands Heart Journal : Monthly... May 2018
PubMed: 29520618
DOI: 10.1007/s12471-018-1101-9 -
Netherlands Heart Journal : Monthly... May 2018
PubMed: 29520619
DOI: 10.1007/s12471-018-1102-8 -
Cardiovascular Research Jan 2022Angiotensin (Ang) II signalling has been suggested to promote cardiac fibrosis in inflammatory heart diseases; however, the underlying mechanisms remain obscure. Using...
AIMS
Angiotensin (Ang) II signalling has been suggested to promote cardiac fibrosis in inflammatory heart diseases; however, the underlying mechanisms remain obscure. Using Agtr1a-/- mice with genetic deletion of angiotensin receptor type 1 (ATR1) and the experimental autoimmune myocarditis (EAM) model, we aimed to elucidate the role of Ang II-ATR1 pathway in development of heart-specific autoimmunity and post-inflammatory fibrosis.
METHODS AND RESULTS
EAM was induced in wild-type (WT) and Agtr1a-/- mice by subcutaneous injections with alpha myosin heavy chain peptide emulsified in complete Freund's adjuvant. Agtr1a-/- mice developed myocarditis to a similar extent as WT controls at day 21 but showed reduced fibrosis and better systolic function at day 40. Crisscross bone marrow chimaera experiments proved that ATR1 signalling in the bone marrow compartment was critical for cardiac fibrosis. Heart infiltrating, bone-marrow-derived cells produced Ang II, but lack of ATR1 in these cells reduced transforming growth factor beta (TGF-β)-mediated fibrotic responses. At the molecular level, Agtr1a-/- heart-inflammatory cells showed impaired TGF-β-mediated phosphorylation of Smad2 and TAK1. In WT cells, TGF-β induced formation of RhoA-GTP and RhoA-A-kinase anchoring protein-Lbc (AKAP-Lbc) complex. In Agtr1a-/- cells, stabilization of RhoA-GTP and interaction of RhoA with AKAP-Lbc were largely impaired. Furthermore, in contrast to WT cells, Agtr1a-/- cells stimulated with TGF-β failed to activate canonical Wnt pathway indicated by suppressed activity of glycogen synthase kinase-3 (GSK-3)β and nuclear β-catenin translocation and showed reduced expression of Wnts. In line with these in vitro findings, β-catenin was detected in inflammatory regions of hearts of WT, but not Agtr1a-/- mice and expression of canonical Wnt1 and Wnt10b were lower in Agtr1a-/- hearts.
CONCLUSION
Ang II-ATR1 signalling is critical for development of post-inflammatory fibrotic remodelling and dilated cardiomyopathy. Our data underpin the importance of Ang II-ATR1 in effective TGF-β downstream signalling response including activation of profibrotic Wnt/β-catenin pathway.
Topics: Angiotensin II; Animals; Autoimmune Diseases; Autoimmunity; CD4-Positive T-Lymphocytes; Cell Proliferation; Cells, Cultured; Disease Models, Animal; Fibrosis; Inflammation Mediators; Lymphocyte Activation; Mice, Inbred BALB C; Mice, Knockout; Myocarditis; Myocytes, Cardiac; Receptor, Angiotensin, Type 1; Wnt Proteins; Wnt Signaling Pathway; Wnt1 Protein; beta Catenin; Mice
PubMed: 33576779
DOI: 10.1093/cvr/cvab039 -
Developmental Cell Nov 2023Despite their burden, most congenital defects remain poorly understood, due to lack of knowledge of embryological mechanisms. Here, we identify Greb1l mutants as a mouse...
Despite their burden, most congenital defects remain poorly understood, due to lack of knowledge of embryological mechanisms. Here, we identify Greb1l mutants as a mouse model of crisscross heart. Based on 3D quantifications of shape changes, we demonstrate that torsion of the atrioventricular canal occurs together with supero-inferior ventricles at E10.5, after heart looping. Mutants phenocopy partial deficiency in retinoic acid signaling, which reflect overlapping pathways in cardiac precursors. Spatiotemporal gene mapping and cross-correlated transcriptomic analyses further reveal the role of Greb1l in maintaining a pool of dorsal pericardial wall precursor cells during heart tube elongation, likely by controlling ribosome biogenesis and cell differentiation. Consequently, we observe growth arrest and malposition of the outflow tract, which are predictive of abnormal tube remodeling in mutants. Our work on a rare cardiac malformation opens novel perspectives on the origin of a broader spectrum of congenital defects associated with GREB1L in humans.
Topics: Humans; Animals; Mice; Crisscross Heart; Morphogenesis; Heart; Heart Ventricles; Stem Cells
PubMed: 37852253
DOI: 10.1016/j.devcel.2023.09.006 -
Annals of Pediatric Cardiology Jan 2014Crisscross heart is a rare congenital heart disease characterized by a twisted atrioventricular connection, as a result of rotation of the ventricular mass along its...
Crisscross heart is a rare congenital heart disease characterized by a twisted atrioventricular connection, as a result of rotation of the ventricular mass along its long axis. We report an asymptomatic 48-year-old woman referred to us for evaluation of a cardiac murmur. Further evaluation showed situs solitus, dextrocardia with normal atrioventricular and ventriculoarterial connection, and a crisscross relation of the atrioventricular valves. Unlike the usual case of crisscross heart, our patient had an intact ventricular septum.
PubMed: 24701094
DOI: 10.4103/0974-2069.126571 -
EuroIntervention : Journal of EuroPCR... May 2016
Topics: Cardiology; Committee Membership; Heart Defects, Congenital; Humans; Surveys and Questionnaires
PubMed: 27173857
DOI: 10.4244/EIJV12I1A4 -
JPMA. the Journal of the Pakistan... Jul 2022Crisscross heart (CCH) is a rare anomaly characterized by twisting of the inflow streams of right and left ventricles. The etiology of CCH is not known. Its frequency is...
Crisscross heart (CCH) is a rare anomaly characterized by twisting of the inflow streams of right and left ventricles. The etiology of CCH is not known. Its frequency is less than 8/10, 00,000 live births. Cyanosis is common in neonatal age, while shortness of breath is the main presenting complaint in older children. We present a case series of CCH with array of associations, diagnosed by echocardiography. CCH is a rare heart defect that can be diagnosed by echocardiography by a vigilant operator. Early diagnosis is the key to successful management resulting in increased survival rate, better outcomes and improved quality of life.
Topics: Child; Crisscross Heart; Echocardiography; Female; Heart Defects, Congenital; Heart Ventricles; Humans; Infant, Newborn; Quality of Life
PubMed: 36156574
DOI: 10.47391/JPMA.3162 -
Texas Heart Institute Journal 1988
Progress in the understanding of congenital heart disease: double-outlet right ventricle {S,D,L}, definition of ventriculoarterial discordance, definition of transposition of the great arteries, and the illusion of crisscross AV relations.
PubMed: 15227249
DOI: No ID Found -
BJR Case Reports Feb 2021A criss-cross heart is an uncommon congenital rotational anomaly. It accounts for less than 0.1% of all congenital heart defects. The anomaly is characterized by...
A criss-cross heart is an uncommon congenital rotational anomaly. It accounts for less than 0.1% of all congenital heart defects. The anomaly is characterized by crossing of the atrioventricular connections caused by rotation of the heart about its long axis. It is commonly associated with diverse cardiac defects. Cardiac CT imaging of criss-cross heart is sparse. We present a case of 1-year-old child with chief complaints of bluish discoloration of the body and fast breathing. Cardiac CT revealed atrial situs solitus, criss-cross-atrioventricular connections, atrioventricular discordance, double outlet right ventricle and dextro-malposed great arteries (Van Praagh S,D,D).
PubMed: 33614117
DOI: 10.1259/bjrcr.20200096 -
JACC. Case Reports May 2021Rare cardiac malpositions are faced with diagnostic challenges and may not follow set rules. The presence of more than one pathology simultaneously makes diagnosis...
Rare cardiac malpositions are faced with diagnostic challenges and may not follow set rules. The presence of more than one pathology simultaneously makes diagnosis challenging. The present case report describes antennal diagnosis topsy-turvy heart with crossed ventricular inlets. ().
PubMed: 34317612
DOI: 10.1016/j.jaccas.2020.12.040