Abstract 107: RNA Seq Transcriptome Analysis Reveals Genes and Pathways Involved in the Cardiac Protection of VCP Against Pressure Overload

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Christiana Leimena ◽  
Xin Chen ◽  
Ning Zhou ◽  
Shaunrick Stoll ◽  
Charles Wang ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Transcriptome Analysis ◽  
Pressure Overload ◽  
Left Ventricular ◽  
P Value ◽  
Type I ◽  
Rna Seq ◽  
Cardiac Protection ◽  
Platelet Factor ◽  
Significant Difference

Aims: We previously showed that the valosin containing protein (VCP), a member of ATPases associated protein, protects the heart against pressure overload induced cardiac hypertrophy and dysfunction in transgenic (TG) mice. The mechanisms remain unknown. We hypothesize that VCP regulated alteration in transcriptome contributes to its cardio-protection by targeting cardiac cell growth and survival. Methods and results: Cardiac-specific VCPTG mice and their litter-matched wild type (WT) mice were subjected to transverse aortic constriction (TAC) for 2 and 5 weeks and compared to the sham mice. By using echocardiography and hemodynamic analysis, cardiac hypertrophy and dysfunction were confirmed in 2 weeks- and 5 weeks- TAC models respectively in WT but not in VCPTG mice. Total RNA was extracted from left ventricular tissues and gene expression was determined by RNA-Seq transcriptome analysis. Upon 2 weeks TAC, 690 differentially expressed genes were identified between VCPTG and WT (Fold Change ≥ 1.5, P value ≤ 0.05). Among these genes, VCPTG TAC mice, compared to WT TAC mice, showed significant activation of the genes linked to transcriptional factors, Protein Kinase CGMP-Dependent Type I ( Prkg1 ) and Kruppel Like factor 15 ( Klf15 ), the known repressors of cardiac hypertrophy under stress. On the contrary, there is significant increase in cardiac hypertrophy associated genes in WT TAC mice, such as myosin light chain 7 ( Myl7 ), periostin ( Postn ) and tropomyosin beta chain ( Tpm2) , and in fetal gene natriuretic peptide A ( Nppa) , but these alterations were not observed in VCPTG TAC mice, which may contribute to repression of cardiac hypertrophy in VCPTG mice. In addition, pro-apoptosis genes, such as platelet factor 4 ( Pf4), Pleckstrin homology like domain A1 ( Phlda1 ) and Radical S-Adenosyl Methionine Domain Containing 2 ( Rsad2 ), are significantly downregulated continually in 2 weeks through 5 weeks TAC in VCPTG mice, but not in WT TAC, which may contribute to the protection of cell survival in VCPTG mice. Conclusion: Significant difference of gene regulation exists between VCPTG and WT in the heart under the pressure overload which may be the mechanism of VCP mediated cardiac protection.

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.

Role of sarcoplasmic reticulum in loss of load-sensitive relaxation in pressure overload cardiac hypertrophy

1994 ◽  
Vol 266 (1) ◽  
pp. H68-H78 ◽  
Author(s):  
C. R. Cory ◽  
R. W. Grange ◽  
M. E. Houston
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cardiac Hypertrophy ◽  
Atpase Activity ◽  
Pressure Overload ◽  
Fold Increase ◽  
Left Ventricular ◽  
Isometric Tension ◽  
Tension Development ◽  
Sequestration Potential

The loss of load-sensitive relaxation observed in the pressure-overloaded heart may reflect a strategy of slowed cytosolic Ca2+ uptake to yield a prolongation of the active state of the muscle and a decrease in cellular energy expenditure. A decrease in the potential of the sarcoplasmic reticulum (SR) to resequester cytosolic Ca2+ during diastole could contribute to this attenuated load sensitivity. To test this hypothesis, both in vitro mechanical function of anterior papillary muscles and the SR Ca2+ sequestration potential of female guinea pig left ventricle were compared in cardiac hypertrophy (Hyp) and sham-operated (Sham) groups. Twenty-one days of pressure overload induced by coarctation of the suprarenal, subdiaphragmatic aorta resulted in a 36% increase in left ventricular mass in the Hyp. Peak isometric tension, the rate of isometric tension development, and the maximal rates of isometric and isotonic relaxation were significantly reduced in Hyp. Load-sensitive relaxation were significantly reduced in Hyp. Load-sensitive relaxation quantified by the ratio of a rapid loading to unloading force step in isotonically contracting papillary muscle was reduced 50% in Hyp muscles. Maximum activity of SR Ca(2+)-adenosinetriphosphatase (ATPase) measured under optimal conditions (37 degrees C; saturating Ca2+) was unaltered, but at low free Ca2+ concentrations (0.65 microM), it was decreased by 43% of the Sham response. Bivariate regression analysis revealed a significant (r = 0.84; P = 0.009) relationship between the decrease in SR Ca(2+)-ATPase activity and the loss of load-sensitive relaxation after aortic coarctation. Stimulation of the SR Ca(2+)-ATPase by the catalytic subunit of adenosine 3',5'-cyclic monophosphate-dependent protein kinase resulted in a 2.6-fold increase for Sham but only a 1.6-fold increase for Hyp. Semiquantitative Western blot radioimmunoassays revealed that the changes in SR Ca(2+)-ATPase activity were not due to decreases in the content of the Ca(2+)-ATPase protein or phospholamban. Our data directly implicate a role for decreased SR function in attenuated load sensitivity. A purposeful downregulation of SR Ca2+ uptake likely results from a qualitative rather than a quantitative change in the ATPase and possibly one of its key regulators, phospholamban.

scholarly journals Latihan Fisik Intesitas Submaksimal dan Kalsitonin Salmon Meningkatkan Kepadatan Tulang Tikus Masa Pertumbuhan

2018 ◽  
Author(s):  
Heru Syarli Lesmana ◽  
Gadis Meinar Sari ◽  
Choesnan Effendi ◽  
Shinta Arisant
Keyword(s):  
Bone Density ◽  
Salmon Calcitonin ◽  
Bone Matrix ◽  
Growth Period ◽  
Control Group ◽  
P Value ◽  
Type I ◽  
Femur Bone ◽  
Risk Increase ◽  
Significant Difference

Bone is a complex tissue consisting of cells and matrix. Mass and thick bone mass has a dynamic addition and subtraction through the process of remodeling (bone matrix absorbed and formed again). Bone is formatted by osteoblast cell and resorption by osteoclast cell. Osteoblasts produce a matrix of osteoid, which is composed mainly of type I collagen, and osteoclast removes bone tissue by removing its mineralized matrix and breaking up the organic bone. Bone remodeling purpose to defend shape and structure of bone. the purpose of this study is to prove that submaximal-intensity exercise and salmon calcitonin improve bone density in growing rat this research method uses design of the randomize posttest only control group design. We compered femur bone density in 24 male norvegicus rats aged 6 weeks that were divided into 4 groups: controls, calcitonin, exercise, combine. Exercise group swam 3 times a week in submaximal intensity, calcitonin group injected synthetic salmon calcitonin 2 iu /100 gram of rat weight every day and combine group did both of it. After 8 weeks, rat femur bone density measured using ultrasound. the result: there are significant differences in bone density between group 1 (control) and group 4 (combine) with p = 0.001, thus the p value &lt;0.05 indicates that there is a significant difference to the average density in both groups. While comparisons to other groups found no significant difference because the value of p&gt; 0.05. the benefits of this research are calcitonin salmon and submaximal-intensity exercise increase the density bone in the growth period. High bone density is mean the bone is strong and health, not porous and fragile so decrease bone fracture risk. increase the bone density in of growth period make the bone get the best mass, and avoid from early osteoporosis.

scholarly journals Leonurine Attenuates Pressure-Overload Cardiac Hypertrophy Induced By Abdominal Aortic Constriction In Rats

2021 ◽  
Author(s):  
Ding Xiaoli ◽  
Yuan Qingqing ◽  
Qian Haibing
Keyword(s):  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Pressure Overload ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Ang Ii ◽  
Aortic Constriction ◽  
Qrt Pcr ◽  
Abdominal Aortic

Abstract Background: Myocardial hypertrophy occurs in many cardiovascular diseases. Leonurine (Leo) is commonly used for cardiovascular and cerebrovascular diseases. However, whether it can prevent cardiac hypertrophy is not known. The aim of this study was to investigate the effect and mechanism of Leonurine (Leo) against pressure-overload cardiac hypertrophy induced by abdominal aortic constriction (AAC) in rats. Methods: To answer this question, we prove it in the following way: Cardiac function was evaluated by hemodynamic; the left ventricle enlargement was measured by heart weight index (HWI) and left ventricular mass index (LVWI); myocardial tissue changes and myocardial cell diameter (MD) were determined by Hematoxylin and eosin (HE) staining; theβ-myosin heavy chain(β-MHC)and atrial natriuretic factor (ANF), which are recognized as a marker of cardiac hypertrophy, were determined by Real-time quantitative PCR (qRT-PCR), then another gene phospholipase C (PLC), inositol triphosphate (IP3), which associated with RAS were determined by Western blot(WB). angiotensin II (Ang II), angiotensin II type 1 receptor (AT1R) were determined by ELISA, WB and qRT-PCR methods. Finally, we measured the level of Ca2+ by microplate method and the protooncogene c-fos and c-myc mRNA in left ventricular myocardium by qRT-PCR.Results: Compare with control group, Leonurine can improve systolic dysfunction; inhibit the increase of left cardiac; inhibit myocardial cells were abnormally large and restrain the changes of cardiac histopathology; decrease the expression of β-MHC, ANF, Ang II, AT1R, c-fos and c-myc mRNA and the protein levels of PLC, IP3, AngII and AT1R in left ventricular myocardium, in addition, the content of Ca2+ also decrease. Conclusion: Therefore, Leonurine can inhibit cardiac hypertrophy induced by AAC and its effects may be associated with RAS.

Abstract 478: FGF23 Expression in Cardiac Fibroblasts Is Augmented by S100/Calgranulins-Mediated Inflammation and Associated With Cardiac Hypertrophy, but Not in Angiotensin II-Induced Cardiac Hypertrophy

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Marion Hofmann Bowman ◽  
Brandon Gardner ◽  
Judy Earley ◽  
Debra L Rateri ◽  
Alan Daugherty ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Cardiac Fibroblasts ◽  
Left Ventricular ◽  
Heart Weight ◽  
Ang Ii ◽  
Wild Type ◽  
Wild Type Littermate ◽  
Transgenic Expression ◽  
Significant Difference

Background: Serum S100A12 and fibroblast growth factor (FGF) 23 are biomarkers for cardiovascular mortality in patients with chronic kidney disease (CKD) and are associated with left ventricular hypertrophy (LVH). FGF23 is induced in cultured cardiac fibroblasts in response to cytokines including IL-6, TNF-a, LPS and S100/calgranulins. Moreover, hBAC-S100 transgenic mice with CKD had increased FGF23 in valvular interstitial cells and exhibited LVH. The present study was designed to examine cardiac FGF23 expression in other murine models of LVH in the absence of CKD. Methods: Hearts from five groups of male mice were studied: (i) C57BL6/J with transgenic expression a bacterial artificial chromosome of the human S100/calgranulins (S1008/9 and S100A12, hBAC-S100), (ii) wild type littermates, (iii) LDLR-/- infused with saline (29 days, 0.9%), (iv) LDLR-/- infused with angiotensin (Ang) II (29 days, 1000 ng/kg/min), and (v) fibroblast specific depletion of angiotensin II type 1a receptor (AT1aR) (S100A4-Cre x AT1aR-/- x LDLR-/-) infused with AngII. Results: hBAC-S100, but not wild type littermate mice, developed significant LVH at 10 months by heart weight/body weight (5.9 ±1.1 mg/g vs. 4.2 ±0.8, p<0.04), decreased E/A ratio, and increased LVPW thickness, and associated with increased expression of FGF23 mRNA and protein in cardiac tissue lysates (2-4 fold increase). Similarly, Ang II induced significant LVH compared to saline infused LDLR-/- mice (6.1±1.3 vs. 3.6 ±0.9 mg/g, p<0.01), and associated with increased mRNA for hypertrophic genes (ANP, BNP, b-MHC, CTGF and Col1a1). However, there was no significant difference in FGF23 mRNA and protein between Ang II and saline infused mice. Cardiac hypertrophy was attenuated in AngII-infused mice with deficiency of AT1aR (S100A4-Cre+/-xAT1aRxLDLR-/-). In vitro, Ang II (100nM) did not induce FGF23 in valvular interstitial fibroblasts or myocytes. Summary: Transgenic expression of S100/calgranulins is sufficient to induce LVH in aged mice with normal renal function, and this is associated with FGF23 expression in cardiac interstitial fibroblasts. Future studies are needed to determine whether cardiac FGF23 promotes LVH in a paracrine manner. However, FGF23 does not play a role in Ang II-induced LVH.

scholarly journals Prevalence of elongated styloid process in Saudi population of Aseer region

2013 ◽  
Vol 07 (04) ◽  
pp. 449-454 ◽  
Author(s):  
Mohammed Asif Shaik ◽  
Sultan Mohammed Kaleem ◽  
Abdul Wahab ◽  
Shahul Hameed ◽  
Keyword(s):  
Age Groups ◽  
Styloid Process ◽  
Frequent Pattern ◽  
P Value ◽  
Type I ◽  
Saudi Population ◽  
Radiographic Appearance ◽  
Panoramic Radiographs ◽  
Elongated Styloid Process ◽  
Significant Difference

ABSTRACT Objective: The study was performed to investigate the prevalence, morphology and calcification pattern of elongated styloid process in Saudi population of Aseer (Southern) region and its relation to gender and sub-age groups. Materials and Methods: This study was analyzed digital panoramic radiographs of 1,162 adults. Any radiograph with questionable styloid process was excluded from the study. The apparent length of the styloid process was measured by a single experienced dental and maxillofacial Radiologist. The elongated styloid process was classified with the radiographic appearance based on the morphology and calcification pattern. The data were analyzed by using Student′s t-test and Chi-square test with P value less than 0.05. Results: A total of 1,085 Digital panoramic radiographs showed elongated styloid process of which 686 (63.2%) were noticed in males and 399 (36.8%) were noticed in female patients. There was a statistical significant difference noticed in the mean difference of elongated styloid process between 20-29, 50-59 and 60 years and above sub-age groups. The elongated styloid process was more prevalent in elderly aged male patients (P < 0.05). Type I morphology with calcified out line (a) was the most frequent pattern of calcification noticed in the present study.Conclusion: The panoramic radiographs are economical, easily accessible and useful diagnostic tool for early detection of elongated styloid process with or without symptoms. However, studies with larger sample size would further help to assess the prevalence of this elongated styloid process in Saudi population of various other regions.

Cacao Bean Polyphenols Inhibit Cardiac Hypertrophy and Systolic Dysfunction in Pressure Overload-induced Heart Failure Model Mice

Planta Medica ◽  
2020 ◽  
Vol 86 (17) ◽  
pp. 1304-1312
Author(s):  
Nurmila Sari ◽  
Yasufumi Katanasaka ◽  
Hiroki Honda ◽  
Yusuke Miyazaki ◽  
Yoichi Sunagawa ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Gene Transcription ◽  
Binding Protein ◽  
Systolic Dysfunction ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Cardiomyocyte Hypertrophy ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal

AbstractPathological stresses such as pressure overload and myocardial infarction induce cardiac hypertrophy, which increases the risk of heart failure. Cacao bean polyphenols have recently gained considerable attention for their beneficial effects on cardiovascular diseases. This study investigated the effect of cacao bean polyphenols on the development of cardiac hypertrophy and heart failure. Cardiomyocytes from neonatal rats were pre-treated with cacao bean polyphenols and then stimulated with 30 µM phenylephrine. C57BL/6j male mice were subjected to sham or transverse aortic constriction surgery and then orally administered with vehicle or cacao bean polyphenols. Cardiac hypertrophy and function were examined by echocardiography. In cardiomyocytes, cacao bean polyphenols significantly suppressed phenylephrine-induced cardiomyocyte hypertrophy and hypertrophic gene transcription. Extracellular signal-regulated kinase 1/2 and GATA binding protein 4 phosphorylation induced by phenylephrine was inhibited by cacao bean polyphenols treatment in the cardiomyocytes. Cacao bean polyphenols treatment at 1200 mg/kg significantly ameliorated left ventricular posterior wall thickness, fractional shortening, hypertrophic gene transcription, cardiac hypertrophy, cardiac fibrosis, and extracellular signal-regulated kinase 1/2 phosphorylation induced by pressure overload. In conclusion, these findings suggest that cacao bean polyphenols prevent pressure overload-induced cardiac hypertrophy and systolic dysfunction by inhibiting the extracellular signal-regulated kinase 1/2-GATA binding protein 4 pathway in cardiomyocytes. Thus, cacao bean polyphenols may be useful for heart failure therapy in humans.

Contractile function in chronic gradually developing subcoronary aortic stenosis

1981 ◽  
Vol 240 (1) ◽  
pp. H80-H84
Author(s):  
B. A. Carabello ◽  
R. Mee ◽  
J. J. Collins ◽  
R. A. Kloner ◽  
D. Levin ◽  
...  
Keyword(s):  
Aortic Stenosis ◽  
Cardiac Hypertrophy ◽  
Cardiac Muscle ◽  
Animal Studies ◽  
Contractile Function ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Stroke Work ◽  
Group A ◽  
Group B

Whether hypertrophied cardiac muscle functions normally or abnormally is a point of controversy in the literature. Most animal studies showing depressed performance of hypertrophied cardiac muscle have used experimental methods in which hypertrophy was produced by acutely imposing a pressure overload on the left or right ventricle, which may cause myocardial injury. To assess the possibility that chronic, slowly developing hypertrophy is associated with normal myocardial function, we developed an experimental model in which increased afterload is imposed gradually on the left ventricle in the dog. A snug band was placed around the aorta beneath the left coronary artery in puppies without producing a stenosis. As the puppies grew, relative aortic stenosis developed as increased cardiac output flowed across that fixed outflow area. One group (group A) of six puppies was banded early, whereas a second group (group B, five puppies) was banded late and served as controls. Left ventricular weight (g) to body weight (kg) ratio remained normal in group B animals (3.9 +/- 0.14), whereas this ratio was increased to 5.3 +/- 0.24 (P < 0.001) in group A animals indicating development of moderate cardiac hypertrophy. Ejection fraction, dP/dt, Vcf, and stroke work per gram of myocardium were virtually identical in both groups. We conclude that moderate, gradually developing cardiac hypertrophy as produced by this model is associated with normal myocardial contractile performance.

scholarly journals Evaluation of left ventricular systolic function by Myocardial Deformation Imaging in asymptomatic HIV patients

2019 ◽  
Vol 16 (2) ◽  
pp. 11-15
Author(s):  
Kunjang Sherpa ◽  
Ram Kishor Sah ◽  
Arun Maskey ◽  
Rabi Malla ◽  
Deewakar Sharma ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Transthoracic Echocardiography ◽  
Global Longitudinal Strain ◽  
Strain Imaging ◽  
Left Ventricular ◽  
Cd4 Count ◽  
P Value ◽  
Hiv Patients ◽  
Significant Difference ◽  
Healthy Control

Background and Aims: Despite improvements in clinical care, evidence from both industrialized and developing countries indicates that the prevalence of subclinical cardiac dysfunction in individuals with well-controlled HIV infection may approach 50% and represent a newly recognized comorbid condition. The aim of our study was to reveal abnormalities in cardiac function using conventional transthoracic echocardiography and left ventricular strain imaging in HIV infected patients without cardiovascular disease. Methods: This was a hospital based, single center descriptive cross-sectional comparative study conducted in National Academy of Medical Sciences (NAMS), Bir Hospital which included HIV patients with baseline examination including a patient medical history, clinical examination, baseline CD4 count, viral load and a standardized transthoracic echocardiography and strain imaging examination and the findings were compared among age and sex frequency matched healthy adult population. Results: Our study enrolled 142 patients out of which 95 HIV positive patients (mean age 36.7±9.2 years with 58% female) and 47 healthy control (mean age 33.7±8 years with 57.4% female). The median duration of HIV diagnosis was 7 years (IQR 2, 10) and median CD4 count was 464 cells/mm3 (IQR 259,750). There was no significant difference in conventional echocardiographic parameters between two groups except for transmitral E velocity that was lower in HIV group (P value of 0.001). The HIV population has lower mean global longitudinal strain (GLS) value of -19.92% ± 2.54 SD compared to the healthy control population with mean of -21.39% ± 1.54 SD(P value of 0.001) and patients with CD4 count less than 300 cell/mm3 had GLS value significantly lower than -18% (P value of 0.05). Conclusion: HIV infected population without established cardiovascular disease have subclinical left ventricular dysfunction revealed by GLS imaging technique.

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