Volume Load-Induced Right Ventricular Failure in Rats Is Not Associated With Myocardial Fibrosis

Hagdorn, Quint A.J.; Kurakula, Kondababu; Koop, Anne-Marie C.; Bossers, Guido P L; Mavrogiannis, Emmanouil; Leusden, Tom van; Feen, Diederik E. van der; Boer, Rudolf A. de; Goumans, Marie–José; Berger, Rolf M. F.

doi:10.3389/fphys.2021.557514

Cited by 6 publications

(4 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also analyzed a potential association between SLIT3 expression and cardiac fibrosis in myocardial samples obtained from normal controls, patients with tetralogy of Fallot, where cardiac fibrosis is anticipated from the pressure overload, 32 and those with ventricular septal defect, where less cardiac fibrosis is anticipated from this volume overload defect. 33 We found that SLIT3 transcript levels were significantly correlated with COL1A1 transcript levels when considering all patient and control samples ( Figure S1B ). Furthermore, higher SLIT3 and COL1A1 transcript levels were found in myocardial samples taken from pressure overload defect patients ( Figure S1B ).…”

Section: Resultsmentioning

confidence: 82%

Stromal Cell-SLIT3/Cardiomyocyte-ROBO1 Axis Regulates Pressure Overload-Induced Cardiac Hypertrophy

Liu,

Li,

Wang

et al. 2024

Circulation Research

View full text Add to dashboard Cite

Recently shown to regulate cardiac development, the secreted axon guidance molecule SLIT3 maintains its expression in the postnatal heart. Despite its known expression in the cardiovascular system after birth, SLIT3 ’s relevance to cardiovascular function in the postnatal state remains unknown. As such, the objectives of this study were to determine the postnatal myocardial sources of SLIT3 and to evaluate its functional role in regulating the cardiac response to pressure overload stress. We first found that SLIT3 transcription was increased in myocardial tissue obtained from patients with congenital heart defects that caused ventricular pressure overload. Immunostaining of hearts from wild type and reporter mice revealed that SLIT3 is secreted by cardiac stromal cells, namely, fibroblasts and vascular mural cells, within the heart. Conditioned media from cardiac fibroblasts and vascular mural cells both stimulated cardiomyocyte hypertrophy in vitro, an effect that was partially inhibited by an anti- SLIT3 antibody. Also, the N-terminal, but not the C-terminal, fragment of SLIT3 and the forced overexpression of SLIT3 stimulated cardiomyocyte hypertrophy and the transcription of hypertrophy-related genes. We next determined that ROBO1 was the most highly expressed roundabout receptor in cardiomyocytes and that ROBO1 mediated SLIT3 ’s hypertrophic effects in vitro. In vivo, Tcf21+ fibroblast and Tbx18+ vascular mural cell–specific knockout of SLIT3 in mice resulted in decreased left ventricle hypertrophy and cardiac fibrosis after the transverse aortic constriction. Furthermore, α-MHC+ cardiomyocyte–specific deletion of ROBO1 also preserved left ventricle function and abrogated hypertrophy, but not fibrosis, after the transverse aortic constriction. Collectively, these results indicate a novel role for the SLIT3 - ROBO1 signaling axis in regulating postnatal cardiomyocyte hypertrophy induced by pressure overload.

show abstract

Section: Resultsmentioning

confidence: 82%

Stromal Cell-SLIT3/Cardiomyocyte-ROBO1 Axis Regulates Pressure Overload-Induced Cardiac Hypertrophy

Liu,

Li,

Wang

et al. 2024

Circulation Research

View full text Add to dashboard Cite

show abstract

“…These studies demonstrated that conventional parameters are susceptible to changes in loading conditions. Hagdorn et al reported that TAPSE remained unchanged in their chronic over-preloading rat model study, while Ees gradually decreased, revealing that TAPSE might miss RV dysfunction in chronic volume overloading conditions ( 8 ). Furthermore, we previously reported that TAPSE was not a significant predictor of mortality in a PH cohort because TAPSE can be pseudo-normalized by a lowered RV afterload in severe tricuspid regurgitation (TR) ( 17 ).…”

Section: Manuscriptmentioning

confidence: 99%

“…Conventional parameters such as tricuspid annular plane systolic excursion (TAPSE), systolic tissue Doppler velocity of the tricuspid annulus (RV S’), and RV fractional area change (FAC) have been currently used for RV function evaluation; however, these conventional parameters have several limitations, one of which is the load-dependency. Their values change depending on the hemodynamic load exerted on the RV, leading to inaccurate assessment of RV function ( 6 – 8 ). Since a diseased RV is consistently under complex loading conditions, load dependency is a significant issue that must be addressed.…”

Section: Introductionmentioning

confidence: 99%

Current trends and latest developments in echocardiographic assessment of right ventricular function: load dependency perspective

Nonaka,

Rätsep,

Obonyo

et al. 2024

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Right ventricle (RV) failure is a common complication of many cardiopulmonary diseases. Since it has a significant adverse impact on prognosis, precise determination of RV function is crucial to guide clinical management. However, accurate assessment of RV function remains challenging owing to the difficulties in acquiring its intricate pathophysiology and imaging its complex anatomical structure. In addition, there is historical attention focused exclusively on the left ventricle assessment, which has led to overshadowing and delayed development of RV evaluation. Echocardiography is the first-line and non-invasive bedside clinical tool for assessing RV function. Tricuspid annular plane systolic excursion (TAPSE), RV systolic tissue Doppler velocity of the tricuspid annulus (RV S'), and RV fractional area change (RV FAC) are conventional standard indices routinely used for RV function assessment, but accuracy has been subject to several limitations, such as load-dependency, angle-dependency, and localized regional assessment. Particularly, load dependency is a vexing issue, as the failing RV is always in a complex loading condition, which alters the values of echocardiographic parameters and confuses clinicians. Recently, novel echocardiographic methods for improved RV assessment have been developed. Specifically, “strain”, “RV-pulmonary arterial (PA) coupling”, and “RV myocardial work” are newly applied methods for RV function assessment, a few of which are designed to surmount the load dependency by taking into account the afterload on RV. In this narrative review, we summarize the latest data on these novel RV echocardiographic parameters and highlight their strengths and limitations. Since load independency is one of the primary advantages of these, we particularly emphasize this aspect.

show abstract

“…Myocardial fibrosis is a manifestation of an adaptive response by the heart to pressure overload. Accordingly, fibroblasts undergo differentiation into myofibroblasts to counter this imposed stress that suppresses cardiac function (Hagdorn et al, 2021). This shift is reflective of a healthy myocardium response in which some of the fibroblast markers that include α‐smooth muscle actin (α‐SMA), collagen I, and collagen III, are not expressed (Czubryt & Hale, 2021; Gritsenko et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Apigenin inhibits isoproterenol‐induced myocardial fibrosis and Smad pathway in mice by regulating oxidative stress and miR‐122‐5p/155‐5p expressions

Wang

Zhang

Niu

et al. 2022

Drug Development Research

View full text Add to dashboard Cite

Apigenin, a flavonoid isolated from Apium graveolens, is an effective natural active ingredient that inhibits transforming growth factor-β1 (TGF-β1)-induced cardiac fibroblasts (CFs) differentiation and collagen synthesis. However, its effects on isoproterenolinduced myocardial fibrosis in mice remain unknown. This study aimed to examine the effect of apigenin in the prevention of myocardial fibrosis. A mouse model of myocardial fibrosis induced by isoproterenol was established, and the mice were given apigenin 75-300 mg/kg orally for 40 days. The results showed that the heart weight coefficient, myocardial hydroxyproline, collagen accumulation, and malondialdehyde levels in the apigenin-treated groups were significantly reduced. In contrast, the activity of myocardial superoxide dismutase and glutathione peroxidase were significantly enhanced. The results of real-time quantitative polymerase chain reaction and western blot assays showed that apigenin could significantly upregulate the expressions of myocardial microRNA-122-5p (miR-122-5p), c-Ski, and Smad7 and downregulate the expressions of myocardial miR-155-5p, α-smooth muscle actin, collagen I/III, NF-κB, TGF-β1, hypoxia-inducible factor-1α (HIF-1α), Smad2/3, and p-Smad2/3. In vitro, the differentiation and extracellular matrix production, as well as TGF-β1/Smads axis, were further reduced after treatment of miR-122-5p mimic or miR-155-5p inhibitor-transfected and TGF-β1-stimulated CFs with apigenin. These results suggested that apigenin increased the expression of miR-122-5p and decreased the expression of miR-155-5p, which subsequently downregulated and upregulated the target genes HIF-1α and c-Ski, respectively. Furthermore, apigenin administration downregulated TGF-β1-induced Smad2/3 and upregulated Smad7. In addition, it reduced the NF-κB/TGF-β1 signaling pathway axis by increasing antioxidant ability to exert the antifibrotic effects.

show abstract

Volume Load-Induced Right Ventricular Failure in Rats Is Not Associated With Myocardial Fibrosis

Cited by 6 publications

References 48 publications

Stromal Cell-SLIT3/Cardiomyocyte-ROBO1 Axis Regulates Pressure Overload-Induced Cardiac Hypertrophy

Stromal Cell-SLIT3/Cardiomyocyte-ROBO1 Axis Regulates Pressure Overload-Induced Cardiac Hypertrophy

Current trends and latest developments in echocardiographic assessment of right ventricular function: load dependency perspective

Apigenin inhibits isoproterenol‐induced myocardial fibrosis and Smad pathway in mice by regulating oxidative stress and miR‐122‐5p/155‐5p expressions

Contact Info

Product

Resources

About