Mechanical modulation of cardiac function: role of the pericardium

2011 ◽  
pp. 281-289 ◽  
Author(s):  
John V. Tyberg
Keyword(s):  
Cardiac Function ◽  
Mechanical Modulation

scholarly journals Neutrophil Elastase Deficiency Ameliorates Myocardial Injury Post Myocardial Infarction in Mice

2021 ◽  
Vol 22 (2) ◽  
pp. 722
Author(s):  
Yukino Ogura ◽  
Kazuko Tajiri ◽  
Nobuyuki Murakoshi ◽  
DongZhu Xu ◽  
Saori Yonebayashi ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Neutrophil Elastase ◽  
Myocardial Injury ◽  
Flow Cytometric Analysis ◽  
Akt Signaling ◽  
Border Zone ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Deficient Mice

Neutrophils are recruited into the heart at an early stage following a myocardial infarction (MI). These secrete several proteases, one of them being neutrophil elastase (NE), which promotes inflammatory responses in several disease models. It has been shown that there is an increase in NE activity in patients with MI; however, the role of NE in MI remains unclear. Therefore, the present study aimed to investigate the role of NE in the pathogenesis of MI in mice. NE expression peaked on day 1 in the infarcted hearts. In addition, NE deficiency improved survival and cardiac function post-MI, limiting fibrosis in the noninfarcted myocardium. Sivelestat, an NE inhibitor, also improved survival and cardiac function post-MI. Flow cytometric analysis showed that the numbers of heart-infiltrating neutrophils and inflammatory macrophages (CD11b+F4/80+CD206low cells) were significantly lower in NE-deficient mice than in wild-type (WT) mice. At the border zone between intact and necrotic areas, the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells was lower in NE-deficient mice than in WT mice. Western blot analyses revealed that the expression levels of insulin receptor substrate 1 and phosphorylation of Akt were significantly upregulated in NE-knockout mouse hearts, indicating that NE deficiency might improve cardiac survival by upregulating insulin/Akt signaling post-MI. Thus, NE may enhance myocardial injury by inducing an excessive inflammatory response and suppressing Akt signaling in cardiomyocytes. Inhibition of NE might serve as a novel therapeutic target in the treatment of MI.

scholarly journals Inhibition of let-7c Regulates Cardiac Regeneration after Cryoinjury in Adult Zebrafish

2019 ◽  
Vol 6 (2) ◽  
pp. 16 ◽  
Author(s):  
Suneeta Narumanchi ◽  
Karri Kalervo ◽  
Sanni Perttunen ◽  
Hong Wang ◽  
Katariina Immonen ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Cardiac Regeneration ◽  
Nuclear Antigen ◽  
Heart Regeneration ◽  
Adult Zebrafish ◽  
Tissue Samples ◽  
Micro Rnas ◽  
Proliferating Cell ◽  
Zebrafish Heart

The let-7c family of micro-RNAs (miRNAs) is expressed during embryonic development and plays an important role in cell differentiation. We have investigated the role of let-7c in heart regeneration after injury in adult zebrafish. let-7c antagomir or scramble injections were given at one day after cryoinjury (1 dpi). Tissue samples were collected at 7 dpi, 14 dpi and 28 dpi and cardiac function was assessed before cryoinjury, 1 dpi, 7 dpi, 14 dpi and 28 dpi. Inhibition of let-7c increased the rate of fibrinolysis, increased the number of proliferating cell nuclear antigen (PCNA) positive cardiomyocytes at 7 dpi and increased the expression of the epicardial marker raldh2 at 7 dpi. Additionally, cardiac function measured with echocardiography recovered slightly more rapidly after inhibition of let-7c. These results reveal a beneficial role of let-7c inhibition in adult zebrafish heart regeneration.

Abstract P199: Mas Receptor Deficiency Regulates Obesity-Hypertension and Cardiac Function in Female and Male Mice

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Robin C Shoemaker ◽  
Yu Wang ◽  
Sean Thatcher ◽  
Lisa Cassis
Keyword(s):  
Blood Pressure ◽  
Sexual Dimorphism ◽  
Cardiac Function ◽  
Male Mice ◽  
Reduced Ejection Fraction ◽  
Obesity Hypertension ◽  
Obese Male ◽  
Deficient Mice ◽  
Cmr Imaging

Angiotensin-1-7 (Ang-(1-7)) counteracts angiotensin II through effects at Mas receptors (MasR). We demonstrated that sexual dimorphism of obesity-hypertension was associated with dysregulated production of Ang-(1-7). However, the role of MasR in sexual dimorphism of obesity-hypertension has not been examined. MasR deficient mice have also been reported to exhibit deficits in cardiac function. In this study, we hypothesized that deficiency of the MasR would differentially regulate obesity-hypertension in male versus ( vs ) female mice. In addition, we quantified effects of MasR deficiency on cardiac function in obese male mice. Male and female MasR +/+ and -/- mice were fed a low fat (LF, 10%kcal) or high fat (HF, 60% kcal) diet for 16 weeks, and blood pressure was quantified by radiotelemetry. As demonstrated previously, male MasR +/+ mice (24 hr diastolic blood pressure, DBP: LF, 90 ± 3; HF, 96 ± 2 mmHg; P<0.05), but not females (LF, 85 ± 1; HF, 85 ± 2 mmHg), developed hypertension in response to HF feeding. MasR deficiency converted female HF-fed mice to an obesity-hypertension phenotype (DBP: 92 ± 1 mmHg; P<0.05). Surprisingly, male HF-fed MasR -/- mice exhibited reduced DBP compared to HF-fed MasR +/+ males (90 ± 1 vs 96 ± 2 mmHg; P<0.05). To define mechanisms for reductions in DBP of HF-fed male MasR -/- mice, we performed cardiac magnetic resonance (CMR) imaging in both genotypes at 1 month of HF feeding. MasR -/- mice had significantly reduced ejection fraction (EF) compared to MasR +/+ mice at baseline (51.4 ± 2.5 vs 59.3 ± 2.1%; P<0.05) and after one month of HF-feeding (49.8 ± 2.4 vs 52.6 ± 1.9%; P<0.05). Further, CMR imaging demonstrated a thickening of the ventricle wall in MasR -/- mice with 1 month of HF-feeding. MasR +/+ , but not MasR -/- mice, exhibited diet-induced reductions in EF (by 16%; P<0.05) at 1 month of HF feeding, which were reversed by infusion of Ang-(1-7). These results demonstrate that MasR contributes to sexual dimorphism of obesity-hypertension. Ang-(1-7) protects females from obesity-hypertension through the MasR. In contrast, reductions in DBP in obese male mice with MasR deficiency may arise from deficits in cardiac function. These results suggest that MasR agonists may be effective therapies for obesity-associated cardiovascular conditions.

Abstract 314: BRaf Plays a Major Role in Gene Expression in Cardiomyocytes in Mouse Hearts in vivo

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Michelle A Hardyman ◽  
Stephen J Fuller ◽  
Daniel N Meijles ◽  
Kerry A Rostron ◽  
Sam J Leonard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cardiac Hypertrophy ◽  
Cardiac Function ◽  
Left Ventricular ◽  
Braf Mutations ◽  
Gene Markers ◽  
Lv Mass ◽  
Cardiac Volumes

Introduction: Raf kinases lie upstream of ERK1/2 with BRaf being the most highly expressed and having the highest basal activity. V600E BRaf mutations constitutively activate ERK1/2 and are common in cancer. The role of BRaf in the adult heart is yet to be established. ERK1/2 regulate cardiomyocyte gene expression, promoting cardiac hypertrophy and cardioprotection, but effects of ERK1/2 may depend on signal strength. Hypothesis: Our hypotheses are that BRaf is critical in regulating ERK1/2 signaling in cardiomyocytes and, whilst moderate ERK1/2 activity is beneficial, excessive ERK1/2 activity is detrimental to the heart. Methods: We generated heterozygote mice for tamoxifen- (Tam-) inducible cardiomyocyte-specific knockin of V600E in the endogenous BRaf gene. Mice (12 wks) received 2 injections of Tam or vehicle on consecutive days (n=4-10 per group). Kinase activities and mRNA expression were assessed by immunoblotting and qPCR. Echocardiography was performed (Vevo2100). M-mode images (short axis view) were analyzed; data for each mouse were normalized to the mean of 2 baseline controls. Results: V600E knockin did not affect overall BRaf or cRaf levels in mouse hearts, but significantly increased ERK1/2 activities within 48 h (1.51±0.05 fold). Concurrently, mRNAs for hypertrophic gene markers including BNP and immediate early genes (IEGs) increased signficantly. At 72 h, expression of BNP, Fosl1, Myc, Ereg and CTGF increased further, other IEGs (Jun, Fos, Egr1, Atf3) declined, and ANF was upregulated. In contrast, expression of α and β myosin heavy chain mRNAs was substantially downregulated (0.46/0.41±0.05 relative to controls). Within 72 h, left ventricular (LV) mass and diastolic LV wall thickness had increased (1.23±0.05 relative to controls), but cardiac function was severely compromised with significant decreases in ejection fraction and cardiac output (0.53/0.68±0.09 relative to controls) associated with increased LV internal diameters and cardiac volumes. Conclusions: Endogenous cardiomyocyte BRaf is sufficient to activate ERK1/2 in mouse hearts and induce cardiac hypertrophy associated with dynamic temporal changes in gene expression. However, excessive activation of ERK1/2 in isolation is detrimental to cardiac function.

Abstract 391: The Pathophysiological Role of MYBPHL in Dilated Cardiomyopathy

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
David Y Barefield ◽  
Megan J Puckelwartz ◽  
Lisa Dellefave-Castillo ◽  
Elizabeth M McNally
Keyword(s):  
Cardiac Function ◽  
Protein C ◽  
Stop Codon ◽  
Binding Protein ◽  
Premature Stop Codon ◽  
Myosin Binding Protein ◽  
Myosin Binding Protein C ◽  
Pathophysiological Role ◽  
Myosin Binding

Background: Cardiomyopathy is a leading cause of heart failure and is highly heritable. One common form of cardiomyopathy is dilated cardiomyopathy (DCM), which currently has over 70 identified genes that have been described as causative for the disease. Genetic testing for DCM employs gene panels and has a sensitivity of mutation detection less than 50%, indicating that additional genes contribute to DCM. Here, we employed whole genome sequencing (WGS) in a family with DCM and heart block who had previously undergone unrevealing genetic testing. We identified a premature stop codon in the MYBPHL gene, a gene that has not previously been linked to DCM as a likely cause of DCM in this family. Myosin binding protein H Like (MyBP-HL) is a muscle-expressed protein bearing structural similarity to myosin binding protein C (MyBP-C), which is commonly mutated gene in cardiomyopathies. Objective: Determine the physiological and pathophysiological role of Mybphl . Results: RNA-seq and qPCR from mouse hearts revealed that Mybphl is highly expressed in the right and left atria with lower expression in the ventricle and virtually no expression in skeletal muscle. As MyBP-HL shares a high homology with the myofilament proteins cardiac myosin binding protein-C and H, we investigated if MyBP-HL is also myofilament-associated. We determined that MyBP-HL protein is myofilament-associated in the atria although not clearly so in ventricle. To assess the requirement of MyBP-HL in cardiac function, we used a mouse model with an insertional disruption of the Mybphl gene. These mice have deficits in in vivo cardiac function, with reduced fractional shortening. In addition, ECG recordings from the Mybphl null mice show conduction system abnormalities affecting atrioventricular conduction. Conclusions: WGS identified a premature stop codon in MYBPHL in human DCM. A mouse model with a disrupted Mybphl gene showed similar pathophysiological features as the humans with reduced ventricular function and cardiac conduction system abnormalities. MyBP-HL is an important protein for normal cardiac function.

Abstract 791: A Critical Role for Bmper (BMP-binding Endothelial cell precursor-derived Regulator) in Cardiac Muscle Mass Regulation during Development and Pressure Overload Induced Hypertrophy

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Monte Willis ◽  
Rongqin Ren ◽  
Cam Patterson
Keyword(s):  
Cardiac Function ◽  
Cardiac Muscle ◽  
Muscle Mass ◽  
Cardiac Development ◽  
Critical Role ◽  
Pressure Overload ◽  
Posterior Wall ◽  
Fractional Shortening

Bone morphogenetic proteins (BMPs) of the TGF-beta superfamily, have been implicated in multiple processes during cardiac development. Our laboratory recently described an unprecedented role for Bmper in antagonizing BMP-2, BMP-4, and BMP-6. To determine the role of Bmper on cardiac development in vivo, we created Bmper null (Bmper −/−) mice by replacing exons 1 and 2 with GFP. Since Bmper −/− mice are perinatally lethal, we determined pre-natal cardiac function of Bmper −/− mice in utero just before birth. By echocardiography, E18.5 Bmper −/− embryos had decreased cardiac function (24.2 +/− 8.1% fractional shortening) compared to Bmper +/− and Bmper +/+ siblings (52.2 +/− 1.6% fractional shortening) (N=4/group). To further characterize the role of Bmper on cardiac function in adult mice, we performed echocardiography on 8-week old male and female Bmper +/− and littermate control Bmper +/+. Bmper +/− mice had an approximately 15% decrease in anterior and posterior wall thickness compared to sibling Bmper +/+ mice at baseline (n=10/group). Cross-sectional areas of Bmper +/− cardiomyocytes were approximately 20% less than wild type controls, indicating cardiomyocyte hypoplasia in adult Bmper +/− mice at baseline. Histologically, no significant differences were identified in representative H&E and trichrome stained adult Bmper +/− and Bmper +/+ cardiac sections at baseline. To determine the effects of Bmper expression on the development of cardiac hypertrophy, both Bmper +/− and Bmper +/+ sibling controls underwent transaortic constriction (TAC), followed by weekly echocardiography. While a deficit was identified in Bmper +/− mice at baseline, both anterior and posterior wall thicknesses increased after TAC, such that identical wall thicknesses were identified in Bmper +/− and Bmper +/+ mice 1–4 weeks after TAC. Notably, cardiac function (fractional shortening %) and histological evaluation revealed no differences between Bmper +/− and Bmper +/+ any time after TAC. These studies identify for the first time that Bmper expression plays a critical role in regulating cardiac muscle mass during development, and that Bmper regulates the development of hypertrophy in response to pressure overload in vivo.

scholarly journals Testosterone modulates cardiomyocyte Ca2+ handling and contractile function

2009 ◽  
pp. 293-297 ◽  
Author(s):  
CL Curl ◽  
LMD Delbridge ◽  
BJ Canny ◽  
IR Wendt
Keyword(s):  
Sex Differences ◽  
Cardiac Function ◽  
Time Course ◽  
Direct Evidence ◽  
Contractile Function ◽  
Testosterone Replacement

The extent to which sex differences in cardiac function may be attributed to the direct myocardial influence of testosterone is unclear. In this study the effects of gonadal testosterone withdrawal (GDX) and replacement (GDX+T) in rats, on cardiomyocyte shortening and intracellular Ca2+ handling was investigated (0.5 Hz, 25 o C). At all extracellular [Ca2+] tested (0.5-2.0 mM), the Ca2+ transient amplitude was significantly reduced (by ~ 50 %) in myocytes of GDX rats two weeks postgonadectomy. The time course of Ca2+ transient decay was significantly prolonged in GDX myocytes (tau, 455±80 ms) compared with intact (279±23 ms) and GDX+T (277±19 ms). Maximum shortening of GDX myocytes was markedly reduced (by more than 60 %) and relaxation significantly delayed (by more than 35 %) compared with intact and GDX+T groups. Thus testosterone replacement completely reversed the cardiomyocyte hypocontractility induced by gonadectomy. These results provide direct evidence for a role of testosterone in regulating functional Ca2+ handling and contractility in the heart.

scholarly journals Garcinoic Acid Improves Cardiac Function and Enhances Angiogenesis Following Myocardial Infarction

2021 ◽  
Author(s):  
Hongyao Hu ◽  
Wei Li ◽  
Yanzhao Wei ◽  
Hui Zhao ◽  
Zhenzhong Wu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Ventricular Remodeling ◽  
Vehicle Group ◽  
Potential Mechanism ◽  
Garcinia Kola ◽  
Angiogenic Proteins

Abstract Cardiac ischemia impairs angiogenesis in response to hypoxia, resulting in ventricular remodeling. Garcinoic acid (GA), the extraction from the plant garcinia kola, is validated to attenuate inflammatory response. However, the role of GA in heart failure (HF) and neovascularization after myocardial infarction (MI) is incompletely understood. The present study is striving to explore the role of GA and the potential mechanism of which in cardiac function after MI. SD rats were randomized into sham group, MI+vehicle group, and MI+GA group in vivo. Human umbilical endothelial cells (HUVECs) were cultured in vehicle or GA, and then additionally exposed to 2% hypoxia environment in vitro. MI rats displayed a dramatically reduced myocardial injury, cardiac function and vessel density in the peri-infarcted areas. GA delivery markedly improved cardiac performance and promoted angiogenesis. In addition, GA significantly enhanced tube formation in HUVECs under hypoxia condition. Furthermore, the expressions of pro-angiogenic factors HIF-1α, VEGF-A and bFGF, and pro-angiogenic proteins phospho-VEGFR2Tyr1175 and VEGFR2, as well as phosphorylation levels of Akt and eNOS were increased by GA treatment. In conclusion, GA preserved cardiac function after MI probably via promoting neovascularization. And the potential mechanism may be partially through upregulating the expressions of HIF-1α, VEGF-A, bFGF, phospho-VEGFR2Tyr1175 and VEGFR2 and activating the phosphorylations of Akt and eNOS.

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