scholarly journals Lack of Contribution of p66shc to Pressure Overload-Induced Right Heart Hypertrophy

2020 ◽  
Vol 21 (24) ◽  
pp. 9339
Author(s):  
Christine Hirschhäuser ◽  
Akylbek Sydykov ◽  
Annemarie Wolf ◽  
Azadeh Esfandiary ◽  
Julia Bornbaum ◽  
...  
Keyword(s):  
Pressure Overload ◽  
Left Ventricular ◽  
Sham Operation ◽  
Ros Production ◽  
Mitochondrial Ros ◽  
Ros Formation ◽  
Pulmonary Arterial ◽  
Genetic Deletion ◽  
And Function ◽  
The Impact

The leading cause of death in pulmonary arterial hypertension (PAH) is right ventricular (RV) failure (RVF). Reactive oxygen species (ROS) have been suggested to play a role in the development of RV hypertrophy (RVH) and the transition to RVF. The hydrogen peroxide-generating protein p66shc has been associated with left ventricular (LV) hypertrophy but its role in RVH is unclear. The purpose of this study was to determine whether genetic deletion of p66shc affects the development and/or progression of RVH and RVF in the pulmonary artery banding (PAB) model of RV pressure overload. The impact of p66shc on mitochondrial ROS formation, RV cardiomyocyte function, as well as on RV morphology and function were studied three weeks after PAB or sham operation. PAB in wild type mice did not affect mitochondrial ROS production or RV cardiomyocyte function, but induced RVH and impaired cardiac function. Genetic deletion of p66shc did also not alter basal mitochondrial ROS production or RV cardiomyocyte function, but impaired RV cardiomyocyte shortening was observed following PAB. The development of RVH and RVF following PAB was not affected by p66shc deletion. Thus, our data suggest that p66shc-derived ROS are not involved in the development and progression of RVH or RVF in PAH.

Pressure overload-induced LV hypertrophy and dysfunction in mice are exacerbated by congenital NOS3 deficiency

2004 ◽  
Vol 286 (3) ◽  
pp. H1070-H1075 ◽  
Author(s):  
Fumito Ichinose ◽  
Kenneth D. Bloch ◽  
Justina C. Wu ◽  
Ryuji Hataishi ◽  
H. Thomas Aretz ◽  
...  
Keyword(s):  
Wall Thickness ◽  
Maximum Rate ◽  
Pressure Overload ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Mouse Strains ◽  
Term Administration ◽  
And Function ◽  
The Impact ◽  
Fractional Shortening

To investigate the role of endothelial nitric oxide synthase (NOS3) in left ventricular (LV) remodeling induced by chronic pressure overload, the impact of transverse aortic constriction (TAC) on LV structure and function was compared in wild-type (WT) and NOS3-deficient (NOS3–/–) mice. Before TAC, LV wall thickness, mass, and fractional shortening were similar in the two mouse strains. Twenty-eight days after TAC, both WT and NOS3–/– mice had increased LV wall thickness and mass as well as decreased fractional shortening. Although the pressure gradient across the TAC was similar in both strains of mice 28 days after TAC, LV mass and posterior wall thickness were greater in NOS3–/– than in WT mice, whereas fractional shortening and the maximum rate of developed LV pressure were less. Diastolic function, as measured by the time constant of isovolumic relaxation and the maximum rate of LV pressure decay, was impaired to a greater extent in NOS3–/– than in WT mice. The degree of myocyte hypertrophy and LV fibrosis was greater in NOS3–/– than in WT mice at 28 days after TAC. Mortality was greater in NOS3–/– than in WT mice 28 days after TAC. Long-term administration of hydralazine normalized the blood pressure and prevented the LV dilation in NOS3–/– mice but did not prevent the LV hypertrophy, dysfunction, and fibrosis associated with NOS3 deficiency after TAC. These results suggest that the absence of NOS3 augments LV dysfunction and remodeling in a murine model of chronic pressure overload.

scholarly journals A short duration of high-fat diet induces insulin resistance and predisposes to adverse left ventricular remodeling after pressure overload

2008 ◽  
Vol 295 (6) ◽  
pp. H2495-H2502 ◽  
Author(s):  
Michael J. Raher ◽  
Helene B. Thibault ◽  
Emmanuel S. Buys ◽  
Darshini Kuruppu ◽  
Nobuyuki Shimizu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Myocardial Perfusion ◽  
Short Duration ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Systemic Hypertension ◽  
High Fat ◽  
Lv Remodeling ◽  
And Function ◽  
The Impact

Insulin resistance is an increasingly prevalent condition in humans that frequently clusters with disorders characterized by left ventricular (LV) pressure overload, such as systemic hypertension. To investigate the impact of insulin resistance on LV remodeling and functional response to pressure overload, C57BL6 male mice were fed a high-fat (HFD) or a standard diet (SD) for 9 days and then underwent transverse aortic constriction (TAC). LV size and function were assessed in SD- and HFD-fed mice using serial echocardiography before and 7, 21, and 28 days after TAC. Serial echocardiography was also performed on nonoperated SD- and HFD-fed mice over a period of 6 wk. LV perfusion was assessed before and 7 and 28 days after TAC. Nine days of HFD induced systemic and myocardial insulin resistance (assessed by myocardial 18F-fluorodeoxyglucose uptake), and myocardial perfusion response to acetylcholine was impaired. High-fat feeding for 28 days did not change LV size and function in nonbanded mice; however, TAC induced greater hypertrophy, more marked LV systolic and diastolic dysfunction, and decreased survival in HFD-fed compared with SD-fed mice. Compared with SD-fed mice, myocardial perfusion reserve was decreased 7 days after TAC, and capillary density was decreased 28 days after TAC in HFD-fed mice. A short duration of HFD induces insulin resistance in mice. These metabolic changes are accompanied by increased LV remodeling and dysfunction after TAC, highlighting the impact of insulin resistance in the development of pressure-overload-induced heart failure.

Impact of mitral regurgitation on left ventricular anatomic and molecular remodeling and systolic function: implication for outcome

2009 ◽  
Vol 296 (6) ◽  
pp. H1727-H1732 ◽  
Author(s):  
Min Pu ◽  
Zhaohui Gao ◽  
Xueqian Zhang ◽  
Duanping Liao ◽  
Daniel K. Pu ◽  
...  
Keyword(s):  
Mitral Regurgitation ◽  
Time Course ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Sham Operation ◽  
Proportional Hazard ◽  
Long Term Outcome ◽  
Lv Remodeling ◽  
And Function ◽  
The Impact

The aim of the study was to assess the impact of mitral regurgitation (MR) on left ventricular (LV) anatomic and molecular remodeling and function and to determine whether early LV remodeling and function predict long-term outcome in experimental organic MR. A new rodent model of chronic MR was created. Twenty-eight rats had surgically induced MR, twelve rats had a sham operation, and twelve rats had no operation. LV diameters, volume, and mass and LV ejection fraction (LVEF) and LV fractional shortening (LVFS) were assessed using echocardiography in the early stage of MR (6 and 12 wk after induction of MR). LV hemodynamics was assessed invasively. Cardiac α- and β-myosin heavy chains and sarco(endo)plasmic reticulum Ca2+-ATPase 2 (SERCA2) were measured to assess molecular remodeling and contractility. Cox's proportional hazard ratios (HR) were used to identify outcome predictors. Early LV dilation was demonstrated in rats with MR when LVEF and LVFS were still normal. LV remodeling was associated with an increase in LV end-diastolic pressure and decrease in maximal change in pressure over time. Shifting of α- to β-myosin and reduced SERCA2 were observed in rats with MR. Cox's proportional hazard analysis showed that LV end-diastolic diameters (HR, 1.2–2.4; P = 0.007) and LV end-diastolic volume (HR, 1.1–1.4; P = 0.005) at 6 wk and LV mass index (HR, 1.1–2.0; P = 0.004) at 12 wk after induction of MR were significantly associated with 1-yr mortality. However, LVEF (HR, 0.7–6.8 for the 6 wk, P > 0.05; and HR, 0.4–3.2 for the 12 wk, P > 0.05) and LVFS (HR, 0.4–1.4 for the 6 wk; and 0.4–3.1 for the 12 wk, P > 0.05) did not predict late death. Chronic MR leads to LV anatomic and cellular remodeling and impaired contractility. The time course of LV remodeling and function changes in the rat model of MR is similar to humans. Prediction of outcome may be achieved by assessments of early LV remodeling.

P4997Raf kinase inhibitor protein of the bone marrow contributes to cardiac fibrogenesis in pressure-overloaded myocardium

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Kazakov ◽  
R Hall ◽  
S N Weber ◽  
A Trouvain ◽  
F Lammert ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Kinase Inhibitor ◽  
Systolic Pressure ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Heart Weight ◽  
Sham Operation ◽  
Ros Production ◽  
Myocardial Remodeling ◽  
Inhibitor Protein

Abstract Background Raf Kinase Inhibitor Protein (RKIP) regulates myocardial remodeling under conditions of enhanced myocardial oxidative stress in pressure-overloaded left ventricle (LV) modulating myocardial production of reactive oxygen species (ROS). A second mode of action may be the mobilization of circulating fibroblasts (fibrocytes) from the bone-marrow (BM). However the underlying mechanisms are incompletely understood. Methods and results To further characterize the role of RKIP in BM cells for myocardial remodeling 10-week-old wild-type (WT) C57BL/6N mice were subjected to transplantation of bone marrow (BMT) from 10-week-old C57BL/6-RKIP-deficient (RKIP−/−) N or WT C57BL/6N mice expressing green fluorescent protein (GFP)+ ubiquitously. 28 days later, transverse aortic constriction (TAC, 360 μm) or SHAM-operation was performed. 5 weeks post TAC, LV systolic pressure (LVSP) and heart weight to tibia length ratio were significantly increased in both types of BMT, compared with corresponding SHAM. Increased afterload elicited myocardial fibrosis as assessed by picrosirius red staining (WT/WT SHAM 15±2.5%, WT/WT TAC 21.3±1.4%, p<0.05; RKIP−/−/WT SHAM 17±2%, RKIP−/−/WT TAC 18±3%, p=ns) and significantly increased the number of LV fibroblasts per mm2 estimated by immunostaining for intracellular fibronectin, which were further reduced by transplantation of RKIP−/−N BM (WT/WT SHAM 5499±313, WT/WT TAC 7493±741 per mm2, p<0.05; RKIP−/−/WT SHAM 5737±259, RKIP−/−/WT TAC 5282±551, per mm2, p=ns). Moreover, transplantation of RKIP−/−N BM significantly diminished the number of circulating BM-derived GFP+ fibroblasts in the peripheral blood and LV myocardium during pressure overload (WT/WT SHAM 961±129, WT/WT TAC 2326±273 per mm2, p<0.05; RKIP−/−/WT SHAM 1041±209, RKIP−/−/WT TAC 1518±107, per mm2, p=ns). The myocardial redox status was assessed by the co-immunostaining for ROS production marker 8-hydroxyguanosin (8-dOHG), cardiomyocyte marker α-sarcomeric actin and fibroblast marker intracellular fibronectin. Pressure overload during 5 weeks significantly increased the percentages of 8-dOHG+cardiomyocytes (WT/WT SHAM 34±9%, WT/WT TAC 63±6%, p<0.05; RKIP−/−/WT SHAM 29±6%, RKIP−/−/WT TAC 31±8%, p=ns) and 8-dOHG+fibroblasts (WT/WT SHAM 57±6%, WT/WT TAC 73±4%, p<0.05; RKIP−/−/WT SHAM 58±2%, RKIP−/−/WT TAC 58±7%, p=ns) in mice transplanted with WT BM but not with RKIP−/−N BM. Conclusions In pressure-overload induced enhanced myocardial ROS production, deficiency of RKIP-expression in the bone marrow abrogates left ventricular fibrosis by reduction of myocardial ROS production and mobilization of BM-derived fibroblasts. These findings suggest that the function of RKIP in the bone marrow may be important for maladaptive myocardial remodelling. Acknowledgement/Funding Deutsche Forschungsgemeinschaft: KA4024/3-1, SFB TRR219; Saarland University HOMFOR, Dr. Marija Orlovich foundation, Corona foundation s199/10060/2014

scholarly journals Pulmonary arterial banding in mice may be a suitable model for studies on ventricular mechanics in pediatric pulmonary arterial hypertension

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Melanie J. Dufva ◽  
Mario Boehm ◽  
Kenzo Ichimura ◽  
Uyen Truong ◽  
Xulei Qin ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Mouse Model ◽  
Arterial Hypertension ◽  
Myocardial Strain ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Suitable Model ◽  
Ventricular Mechanics ◽  
Pulmonary Arterial ◽  
The Impact

Abstract Background The role of interventricular mechanics in pediatric pulmonary arterial hypertension (PAH) and its relation to right ventricular (RV) dysfunction has been largely overlooked. Here, we characterize the impact of maintained pressure overload in the RV–pulmonary artery (PA) axis on myocardial strain and left ventricular (LV) mechanics in pediatric PAH patients in comparison to a preclinical PA-banding (PAB) mouse model. We hypothesize that the PAB mouse model mimics important aspects of interventricular mechanics of pediatric PAH and may be beneficial as a surrogate model for some longitudinal and interventional studies not possible in children. Methods Balanced steady-state free precession (bSSFP) cardiovascular magnetic resonance (CMR) images of 18 PAH and 17 healthy (control) pediatric subjects were retrospectively analyzed using CMR feature-tracking (FT) software to compute measurements of myocardial strain. Furthermore, myocardial tagged-CMR images were also analyzed for each subject using harmonic phase flow analysis to derive LV torsion rate. Within 48 h of CMR, PAH patients underwent right heart catheterization (RHC) for measurement of PA/RV pressures, and to compute RV end-systolic elastance (RV_Ees, a measure of load-independent contractility). Surgical PAB was performed on mice to induce RV pressure overload and myocardial remodeling. bSSFP-CMR, tagged CMR, and intra-cardiac catheterization were performed on 12 PAB and 9 control mice (Sham) 7 weeks after surgery with identical post-processing as in the aforementioned patient studies. RV_Ees was assessed via the single beat method. Results LV torsion rate was significantly reduced under hypertensive conditions in both PAB mice (p = 0.004) and pediatric PAH patients (p < 0.001). This decrease in LV torsion rate correlated significantly with a decrease in RV_Ees in PAB (r = 0.91, p = 0.05) and PAH subjects (r = 0.51, p = 0.04). In order to compare combined metrics of LV torsion rate and strain parameters principal component analysis (PCA) was used. PCA revealed grouping of PAH patients with PAB mice and control subjects with Sham mice. Similar to LV torsion rate, LV global peak circumferential, radial, and longitudinal strain were significantly (p < 0.05) reduced under hypertensive conditions in both PAB mice and children with PAH. Conclusions The PAB mouse model resembles PAH-associated myocardial mechanics and may provide a potential model to study mechanisms of RV/LV interdependency.

Bioengineered Cardiac Grafts

Circulation ◽  
2000 ◽  
Vol 102 (suppl_3) ◽  
Author(s):  
Jonathan Leor ◽  
Sharon Aboulafia-Etzion ◽  
Ayelet Dar ◽  
Lilia Shapiro ◽  
Israel M. Barbash ◽  
...  
Keyword(s):  
Cardiac Tissue ◽  
Left Ventricular ◽  
Cardiac Cells ◽  
Sham Operation ◽  
Complete Disappearance ◽  
3 Dimensional ◽  
Infarcted Myocardium ◽  
Lv Remodeling ◽  
And Function ◽  
Conducive Environment

Background —The myocardium is unable to regenerate because cardiomyocytes cannot replicate after injury. The heart is therefore an attractive target for tissue engineering to replace infarcted myocardium and enhance cardiac function. We tested the feasibility of bioengineering cardiac tissue within novel 3-dimensional (3D) scaffolds. Methods and Results —We isolated and grew fetal cardiac cells within 3D porous alginate scaffolds. The cell constructs were cultured for 4 days to evaluate viability and morphology before implantation. Light microscopy revealed that within 2 to 3 days in culture, the dissociated cardiac cells form distinctive, multicellular contracting aggregates within the scaffold pores. Seven days after myocardial infarction, rats were randomized to biograft implantation (n=6) or sham-operation (n=6) into the myocardial scar. Echocardiography study was performed before and 65±5 days after implantation to assess left ventricular (LV) remodeling and function. Hearts were harvested 9 weeks after implantation. Visual examination of the biograft revealed intensive neovascularization from the neighboring coronary network. Histological examination revealed the presence of myofibers embedded in collagen fibers and a large number of blood vessels. The specimens showed almost complete disappearance of the scaffold and good integration into the host. Although control animals developed significant LV dilatation accompanied by progressive deterioration in LV contractility, in the biograft-treated rats, attenuation of LV dilatation and no change in LV contractility were observed. Conclusions —Alginate scaffolds provide a conducive environment to facilitate the 3D culturing of cardiac cells. After implantation into the infarcted myocardium, the biografts stimulated intense neovascularization and attenuated LV dilatation and failure in experimental rats compared with controls. This strategy can be used for regeneration and healing of the infarcted myocardium.

Dose-dependent effect of ANG II-receptor antagonist on myocyte remodeling in rat cardiac hypertrophy

1997 ◽  
Vol 273 (4) ◽  
pp. H1824-H1831 ◽  
Author(s):  
Masakazu Obayashi ◽  
Masafumi Yano ◽  
Michihiro Kohno ◽  
Shigeki Kobayashi ◽  
Taketo Tanigawa ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Receptor Antagonist ◽  
Pressure Overload ◽  
Wall Stress ◽  
Treated Group ◽  
Left Ventricular ◽  
Abdominal Aortic ◽  
Significant Difference ◽  
And Function ◽  
Vehicle Treated Group

The goal of this study was to examine the effect of an angiotensin II type 1 (AT1)-receptor antagonist (TCV-116) on left ventricular (LV) geometry and function during the development of pressure-overload LV hypertrophy. A low (LD; 0.3 mg ⋅ kg−1 ⋅ day−1) or a high (HD; 3.0 mg ⋅ kg−1 ⋅ day−1) dose of TCV-116 was administered to abdominal aortic-banded rats over 4 wk, and hemodynamics and morphology were then evaluated. In both LD and HD groups, peak LV pressures were decreased to a similar extent compared with the vehicle-treated group but stayed at higher levels than in the sham-operated group. In the LD group, both end-diastolic wall thickness (3.08 ± 0.14 mm) and myocyte width (13.3 ± 0.1 μm) decreased compared with those in the vehicle-treated group (3.67 ± 0.19 mm and 15.3 ± 0.1 μm, respectively; both P < 0.05). In the HD group, myocyte length was further decreased (HD: 82.6 ± 2.6, LD: 94.1 ± 2.9 μm; P < 0.05) in association with a reduction in LV midwall radius (HD: 3.36 ± 0.12, LD: 3.60 ± 0.14 mm; P < 0.05) and peak midwall fiber stress (HD: 69 ± 8, LD: 83 ± 10 × 103dyn/cm2; P < 0.05). There was no significant difference in cardiac output among all groups. The AT1-receptor antagonist TCV-116 induced an inhibition of the development of pressure-overload hypertrophy. Morphologically, not only the width but also the length of myocytes was attenuated with TCV-116, leading to a reduction of midwall radius and hence wall stress, which in turn may contribute to a preservation of cardiac output.

Abstract P311: Blocking Succinate Release Enhances Mitochondrial Reactive Oxygen Species Generation And Worsens Ischemia-reperfusion Injury

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Alexander S Milliken ◽  
Sergiy M Nadtochiy ◽  
Paul S Brookes
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Reactive Oxygen Species Generation ◽  
Ros Generation ◽  
Ros Production ◽  
Succinate Oxidation ◽  
Fluorescence Measurements ◽  
Mitochondrial Ros ◽  
The Impact ◽  
Infarction Heart

Succinate is a metabolite that plays a central role in ischemia-reperfusion (IR) injury,which is relevant to myocardial infarction (heart attack) and stroke. Succinateaccumulates during ischemia and is rapidly consumed at reperfusion driving reactiveoxygen species (ROS) generation at complex-I (Cx-I) and III of the mitochondrial electrontransport chain. This ROS production triggers cell-death, leading to tissue necrosis.Although succinate oxidation has been extensively studied and exploited as a noveltherapeutic target, only 1/3 of the succinate accumulated in ischemia is oxidized atreperfusion, with the remaining 2/3 being released from the cell via monocarboxylatetransporter 1 (MCT1). Extracellular succinate is thought to be pro-inflammatory, and ithas been proposed that preventing succinate release may be therapeutically beneficial.To determine the impact of preventing succinate release on IR injury, we comparedfunctional recovery (i.e. rate x pressure product, RPP) and infarction (i.e. tissue necrosis)of Langendorff perfused mouse hearts treated with an MCT1 inhibitor, AR-C155858,versus vehicle control. This revealed that succinate retention worsens IR injury (i.e.increased infarction and decreased functional recovery) likely due to increased ROS. Totest this hypothesis, we utilized a Langendorff apparatus positioned within aspectrofluorimeter, which permits real-time fluorescence measurements in beatingmouse hearts. Using the mitochondria targeted superoxide probe, MitoSOX red tomeasure ROS production at reperfusion + AR-C155858, demonstrated that succinateretention leads to enhanced mitochondrial ROS generation at the onset of reperfusion.Overall, these results suggest that inhibiting succinate release in the context of IR injurymay not be a viable therapeutic approach, regardless of any downstream anti-inflammatory effects.

Abstract 89: 17beta-Estradiol-activated Estrogen Receptors Attenuate Cardiac Fibrosis Through Inhibition of Collagen I and III Expression in Female Hearts

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Elke Dworatzek ◽  
Shokoufeh Mahmoodzadeh ◽  
Christina Westphal ◽  
Daniela Fliegner ◽  
Vera Regitz-Zagrosek
Keyword(s):  
Estrogen Receptors ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Collagen I ◽  
Sham Operation ◽  
Female Rat ◽  
Female Mice ◽  
Gene And Protein Expression

Objectives: Female pressure-overloaded hearts show less fibrosis compared with males. 17β-Estradiol (E2) attenuates cardiac fibrosis in female mice. Whether this is mediated by direct E2-effects on collagen synthesis is still unknown. Therefore, we investigated the role of E2 and estrogen receptors (ER) on collagen I and III expression and analyzed involved mechanisms. Methods: Female C57BL/6J mice (7 weeks) underwent sham operation, ovariectomy (OVX), OVX with E2-supplementation (390mg E2-containing pellets) or placebo. After 2 weeks, animals underwent transverse aortic constriction (TAC) or sham surgery. Mice were sacrificed after 9 weeks. Collagen amount, collagen I and III protein in left ventricular tissue were detected by Sirius Red and antibody staining, respectively. Gene and protein expression were determined by quantitative Real-Time PCR and Western blot. Adult female rat cardiac fibroblasts were treated with E2 (10 -8 M), vehicle, ERα- and β-agonists (10 -7 M) for 24h or pre-treated with PD98059 for 1h. ER binding to the collagen I and III promoter was analyzed by chromatin immunoprecipitation assays. Findings: In female OVX mice, undergoing TAC surgery, E2-supplementation significantly reduced collagen deposition, collagen I and III mRNA and protein levels in comparison with mice without E2. In female rat cardiac fibroblasts, E2 significantly down-regulated collagen I and III mRNA and protein level. Specific ER-agonist-treatment showed that E2-mediated regulation of collagen I and III expression was mediated via activation of ERα, but not ERβ. Further, upon E2-treatment, ERα was phosphorylated at Ser118, which occurred by E2-induced activation of ERK1/2 signaling. Furthermore, we could show that ERα and ERβ bind to two putative half-palindromic estrogen response elements within the collagen I and III promoter in female cardiac fibroblasts. Conclusion: E2 inhibits cardiac collagen I and III mRNA and protein in female mice under pressure overload. Data from rat female cardiac fibroblasts suggest that this is mediated via E2-activated ERK1/2 signaling and ERα, which binds with ERβ to the collagen I and III promoter. Understanding of how E2/ER attenuate collagen I and III expression in pathological hypertrophy may improve therapy.

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