Regulation of mRNA-expression of the sarcolemmal calmodulin-dependent calcium pump in cardiac hypertrophy

1998 ◽  
pp. 89-104
Author(s):  
B. Krain ◽  
A. Hammes ◽  
L. Neyses
Keyword(s):  
Cardiac Hypertrophy ◽  
Mrna Expression ◽  
Calcium Pump

P3486Experimental model for heart failure in rats: apelin-13/apj and bnp-45 gene expression analysis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H R Helmi ◽  
A P Sunjaya ◽  
D Limanan ◽  
A R Prijanti ◽  
S W A Jusman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Mrna Expression ◽  
Rat Model ◽  
Control Group ◽  
P Value ◽  
Sprague Dawley ◽  
Hypoxia Exposure ◽  
Systemic Hypoxia

Abstract Background Apelin, an adipokine peptide and its receptor has recently emerged as a key signaling pathway in maintaining cardiac performance at chronic pressure loads. Apelin has been linked to ventricular dysfunction and therefore maybe of pathophysiologic relevance as a candidate biomarker in HF patients. Purpose This study aims to investigate Apelin-13 gene expression and level, and Apelin receptor (APJ) level in a rat model of heart failure induced by chronic systemic hypoxia and their correlation to BNP-45 gene expression and level, the current gold standard biomarker for heart failure, and to cardiac histopathologic changes. The effect of chronic systemic hypoxia on cardiac hypertrophy, remodeling and heart failure parameters is also of interest. Methods Twenty-eight male Sprague-Dawley rats (8–12 weeks of age) were placed in special hypoxic chambers divided into 7 groups – a control group provided with normoxia (atmospheric O2 levels) and 6 exposure groups exposed to hypoxia (8% O2) for 6 hours, 1, 3, 5, 7 and 14 days respectively prior to measurement. Changes in the expression of Apelin and BNP-45 were measured using quantitative real-time PCR, whereas changes in Apelin-13, APJ and BNP-45 levels were measured using ELISA. Histopathology staining using Hematoxylin and Eosin was performed on cardiac tissues post-termination. Results Compared to control, BNP-45 mRNA expression in the hypoxic heart was only significantly different in day 14, whereas, Apelin mRNA expression had showed significantly higher values starting from day 7 onward. This is in line with the evidence of cardiac hypertrophy based on histopathologic examination present from day 7 onwards. BNP-45 and Apelin-13 levels were significantly higher compared to control from day 5 onwards with a peak on day 7. Although significantly higher than control, Apelin-13 and BNP-45 level decreases in day 14 as compared to day 7. Mean APJ levels showed a similar profile with Apelin-13 and BNP-45 levels with a peak in day 7 (4.619 ng/mL). The cardiac Apelin-13 level shows strong significant correlation with BNP-45 levels (r 0.823, p-value 0.0001). There was also a strong significant correlation between APJ receptor levels with Apelin-13 (r 0.9029, p-value 0.001) and BNP-45 (r 0.9062, p-value 0.0009) levels. Apelin-13, APJ and BNP-45 levels also showed strong significant positive correlation to the duration of hypoxia exposure. Conclusion Chronic (≥5 days) and not acute systemic hypoxia in an experimental rat model leads to increase in Apelin-13, APJ and BNP-45 levels. Apelin-13 and BNP-45 were found to significantly increase from 5 days onwards. Apelin mRNA expression was found to show significant increase earlier compared to BNP-45 mRNA expression. Hence, Apelin may serve as a new candidate biomarker for detection of HF due to oxidative stress compared to BNP-45. Exposure to chronic systemic hypoxia can serve as an easily replicable rat model for heart failure. Acknowledgement/Funding Department of Biochemistry and Molecular Biology, Faculty of Medicine, Tarumanagara University, Jakarta, Indonesia

Effects of triiodo-thyronine on angiotensin-induced cardiomyocyte hypertrophy: reversal of increased β-myosin heavy chain gene expression

2006 ◽  
Vol 84 (8-9) ◽  
pp. 935-941 ◽  
Author(s):  
Baohua Wang ◽  
Jingping Ouyang ◽  
Zhengyuan Xia
Keyword(s):  
Gene Expression ◽  
Angiotensin Ii ◽  
Thyroid Hormone ◽  
Cardiac Hypertrophy ◽  
Atpase Activity ◽  
Mrna Expression ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Ang Ii ◽  
Hypertrophic Growth

Thyroid hormone-induced cardiac hypertrophy is similar to that observed in physiological hypertrophy, which is associated with high cardiac contractility and increased α-myosin heavy chain (α-MHC, the high ATPase activity isoform) expression. In contrast, angiotensin II (Ang II) induces an increase in myocardial mass with a compromised contractility accompanied by a shift from α-MHC to the fetal isoform β-MHC (the low ATPase activity isoform), which is considered as a pathological hypertrophy and inevitably leads to the development of heart failure. The present study is designed to assess the effect of thyroid hormone on angiotensin II-induced hypertrophic growth of cardiomyocytes in vitro. Cardiomyocytes were prepared from hearts of neonatal Wistar rats. The effects of Ang II and 3,3′,5-triiodo-thyronine (T3) on incorporations of [3H]-thymine and [3H]-leucine, MHC isoform mRNA expression, PKC activity, and PKC isoform protein expression were studied. Ang II enhanced [3H]-leucine incorporation, β-MHC mRNA expression, PKC activity, and PKCε expression and inhibited α-MHC mRNA expression in cardiomyocytes. T3 treatment prevented Ang II-induced increases in PKC activity, PKCε, and β-MHC mRNA overexpression and favored α-MHC mRNA expression. Thyroid hormone appears to be able to reprogram gene expression in Ang II-induced cardiac hypertrophy, and a PKC signal pathway may be involved in such remodeling process.

scholarly journals Deletion of miRNA-22 Induces Cardiac Hypertrophy in Females but Attenuates Obesogenic Diet-Mediated Metabolic Disorders

2020 ◽  
Vol 54 (6) ◽  
pp. 1199-1217
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Cardiac Hypertrophy ◽  
Mrna Expression ◽  
Metabolic Disorders ◽  
Body Weight Gain ◽  
Expression Profiles ◽  
Left Ventricular ◽  
Sequencing Analysis ◽  
Obesogenic Diet

Background/Aims: Obesity is a risk factor associated with cardiometabolic complications. Recently, we reported that miRNA-22 deletion attenuated high-fat diet-induced adiposity and prevented dyslipidemia without affecting cardiac hypertrophy in male mice. In this study, we examined the impact of miRNA-22 in obesogenic diet-induced cardiovascular and metabolic disorders in females. Methods: Wild type (WT) and miRNA-22 knockout (miRNA-22 KO) females were fed a control or an obesogenic diet. Body weight gain, adiposity, glucose tolerance, insulin tolerance, and plasma levels of total cholesterol and triglycerides were measured. Cardiac and white adipose tissue remodeling was assessed by histological analyses. Echocardiography was used to evaluate cardiac function and morphology. RNA-sequencing analysis was employed to characterize mRNA expression profiles in female hearts. Results: Loss of miRNA-22 attenuated body weight gain, adiposity, and prevented obesogenic diet-induced insulin resistance and dyslipidemia in females. WT obese females developed cardiac hypertrophy. Interestingly, miRNA-22 KO females displayed cardiac hypertrophy without left ventricular dysfunction and myocardial fibrosis. Both miRNA-22 deletion and obesogenic diet changed mRNA expression profiles in female hearts. Enrichment analysis revealed that genes associated with regulation of the force of heart contraction, protein folding and fatty acid oxidation were enriched in hearts of WT obese females. In addition, genes related to thyroid hormone responses, heart growth and PI3K signaling were enriched in hearts of miRNA-22 KO females. Interestingly, miRNA-22 KO obese females exhibited reduced mRNA levels of Yap1, Egfr and Tgfbr1 compared to their respective controls. Conclusion: This study reveals that miRNA-22 deletion induces cardiac hypertrophy in females without affecting myocardial function. In addition, our findings suggest miRNA-22 as a potential therapeutic target to treat obesity-related metabolic disorders in females.

scholarly journals Thyroid Hormone-Induced Cardiac Mechano Growth Factor Expression Depends on Beating Activity

Endocrinology ◽  
2010 ◽  
Vol 151 (2) ◽  
pp. 830-838 ◽  
Author(s):  
Miriam van Dijk-Ottens ◽  
Ingrid H. C. Vos ◽  
Peter W. A. Cornelissen ◽  
Alain de Bruin ◽  
Maria E. Everts
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Thyroid Hormone ◽  
Cardiac Hypertrophy ◽  
Mrna Expression ◽  
Left Ventricular ◽  
Neonatal Rat ◽  
Rat Cardiomyocytes ◽  
Mechano Growth Factor ◽  
Physiological Cardiac Hypertrophy

The mechano growth factor (MGF), a splice variant of the IGF-I gene, was first discovered in mechanically overloaded skeletal muscle and was shown to play an important role in proliferation of muscle stem cells. Since then, the presence and effects of MGF have been demonstrated in other tissues. MGF has been shown to act neuroprotectively during brain ischemia, and pretreatment with MGF before myocardial infarction improves cardiac function. Because MGF plays a permissive role in exercise-induced skeletal muscle hypertrophy, we hypothesize that MGF is commonly involved in cardiac hypertrophy. To investigate the regulation of MGF expression in heart, mice were treated with thyroid hormone (T3) for 12 d to induce physiological cardiac hypertrophy. MGF mRNA expression was specifically increased in midregions of the septum and left ventricular wall. Interestingly, MGF expression strongly correlated with the increased or decreased beating frequency of hyperthyroid and hypothyroid hearts. To further investigate the mechanically dependent induction of MGF, neonatal rat cardiomyocytes were isolated and exposed to T3. Upon T3 treatment, cardiomyocytes increased both contractile activity measured as beats per minute and MGF as well as IGF-IEa mRNA expression. Importantly, when cardiomyocytes were contractile arrested by KCl, simultaneous exposure to T3 prevented the up-regulation of MGF, whereas IGF-IEa was still induced. These studies demonstrated that MGF but not IGF-IEa expression is dependent on beating activity. These findings suggest that MGF is specifically stimulated by mechanical loading of the heart to mediate the hypertrophic response to thyroid hormone.

scholarly journals Physiological and pathological cardiac hypertrophy induce different molecular phenotypes in the rat

2001 ◽  
Vol 281 (6) ◽  
pp. R2029-R2036 ◽  
Author(s):  
Motoyuki Iemitsu ◽  
Takashi Miyauchi ◽  
Seiji Maeda ◽  
Satoshi Sakai ◽  
Tsutomu Kobayashi ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Mrna Expression ◽  
Adrenergic Receptor ◽  
Spontaneously Hypertensive Rat ◽  
Left Ventricular ◽  
Control Group ◽  
Trained Group ◽  
Pathological Cardiac Hypertrophy ◽  
Physiological Cardiac Hypertrophy ◽  
Molecular Phenotypes

Pressure overload, such as hypertension, to the heart causes pathological cardiac hypertrophy, whereas chronic exercise causes physiological cardiac hypertrophy, which is defined as athletic heart. There are differences in cardiac properties between these two types of hypertrophy. We investigated whether mRNA expression of various cardiovascular regulating factors differs in rat hearts that are physiologically and pathologically hypertrophied, because we hypothesized that these two types of cardiac hypertrophy induce different molecular phenotypes. We used the spontaneously hypertensive rat (SHR group; 19 wk old) as a model of pathological hypertrophy and swim-trained rats (trained group; 19 wk old, swim training for 15 wk) as a model of physiological hypertrophy. We also used sedentary Wistar-Kyoto rats as the control group (19 wk old). Left ventricular mass index for body weight was significantly higher in SHR and trained groups than in the control group. Expression of brain natriuretic peptide, angiotensin-converting enzyme, and endothelin-1 mRNA in the heart was significantly higher in the SHR group than in control and trained groups. Expression of adrenomedullin mRNA in the heart was significantly lower in the trained group than in control and SHR groups. Expression of β1-adrenergic receptor mRNA in the heart was significantly higher in SHR and trained groups than in the control group. Expression of β1-adrenergic receptor kinase mRNA, which inhibits β1-adrenergic receptor activity, in the heart was markedly higher in the SHR group than in control and trained groups. We demonstrated for the first time that the manner of mRNA expression of various cardiovascular regulating factors in the heart differs between physiological and pathological cardiac hypertrophy.

scholarly journals Diurnal profiling of neuroendocrine genes in murine heart, and shift in proopiomelanocortin gene expression with pressure-overload cardiac hypertrophy

2008 ◽  
Vol 41 (3) ◽  
pp. 117-124 ◽  
Author(s):  
Jennifer A Chalmers ◽  
Shuo-Yen J Lin ◽  
Tami A Martino ◽  
Sara Arab ◽  
Peter Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Cardiac Hypertrophy ◽  
Mrna Expression ◽  
Leptin Receptor ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Pressure Overload ◽  
Pcr Analysis

Neuroendocrine peptides express biologic activity relevant to the cardiovascular system, including regulating heart rate and blood pressure, though little is known about the mechanisms involved. Here, we investigated neuroendocrine gene expression underlying diurnal physiology of the heart. We first used microarray and RT-PCR analysis and demonstrate the simultaneous expression of neuroendocrine genes in normal murine heart, including POMC, GnRH, neuropeptide Y, leptin receptor, GH-releasing hormone, cocaine- and amphetamine-regulated transcript, proglucagon, and galanin. We examined diurnal gene expression profiles, with cosinar bioinformatics to evaluate statistically significant rhythms. The POMC gene exhibits a day/night, circadian or diurnal, pattern of expression in heart, and we postulated that this may be important to cardiac growth and renewal. POMC diurnal gene rhythmicity is altered in pressure-overload cardiac hypertrophy, when compared with control heart, and levels increased at the dark-to-light transition times. These findings are also consistent with the proposal that neuropeptides mediate adverse remodeling processes, such as occur in pathologic hypertrophy. To investigate cellular responses, we screened three cell lines representing fibroblasts, cardiac myocytes, and vascular smooth muscle cells (NIH3T3, heart line 1, and mouse vascular smooth muscle cell line 1 (Movas-1) respectively). POMC mRNA expression is the most notable in Movas-1 cells and, furthermore, exhibits rhythmicity with culture synchronization. Taken together, these results highlight the diverse neuroendocrine mRNA expression profiles in cardiovasculature, and provide a novel model vascular culture system to research the role these neuropeptides play in organ health, integrity, and disease.

Brain natriuretic peptide appears to act locally as an antifibrotic factor in the heart

2001 ◽  
Vol 79 (8) ◽  
pp. 723-729 ◽  
Author(s):  
Yoshihiro Ogawa ◽  
Naohisa Tamura ◽  
Hideki Chusho ◽  
Kazuwa Nakao
Keyword(s):  
Cardiac Hypertrophy ◽  
Mrna Expression ◽  
Natriuretic Peptide ◽  
Guanylyl Cyclase ◽  
Cardiac Fibrosis ◽  
Cardiac Myocyte ◽  
Transforming Growth Factor ◽  
Systemic Hypertension ◽  
Receptor Subtype ◽  
Electron Microscopic

In addition to cardiac myocyte hypertrophy, proliferation and increased extracellular matrix production of cardiac fibroblasts occur in response to cardiac overload. This remodeling of the cardiac interstitium is a major determinant of pathologic hypertrophy leading to ventricular dysfunction and heart failure. Atrial and brain natriuretic peptides (ANP and BNP) are cardiac hormones produced primarily by the atrium and ventricle, respectively. Plasma ANP and BNP concentrations are elevated in patients with hypertension, cardiac hypertrophy, and acute myocardial infarction, suggesting their pathophysiologic roles in these disorders. ANP and BNP exhibit diuretic, natriuretic, and vasodilatory activities via a guanylyl cyclase-coupled natriuretic peptide receptor subtype (guanylyl cyclase-A or GC-A). Here we report the generation of mice with targeted disruption of BNP (BNP–/– mice). We observed focal fibrotic lesions in ventricles from BNP–/– mice with a remarkable increase in ventricular mRNA expression of ANP, angiotensin converting enzyme (ACE), transforming growth factor (TGF)-β3, and pro-α1(I) collagen [Col α1(I)], which are implicated in the generation and progression of ventricular fibrosis. Electron microscopic examination revealed supercontraction of sarcomeres and disorganized myofibrils in some ventricular myocytes from BNP–/– mice. No signs of cardiac hypertrophy and systemic hypertension were noted in BNP–/– mice. In response to acute cardiac pressure overload induced by aortic constriction, massive fibrotic lesions were found in all the BNP–/– mice examined, accompanied by further increase of mRNA expression of TGF-β3 and Col α1(I). We postulate that BNP acts as a cardiocyte-derived antifibrotic factor in the ventricle.Key words: atrial natriuretic peptide, brain natiuretic peptide, cardiac fibrosis, guanylyl cyclase.

scholarly journals The Role of Beta-carotene Metabolism in Maternal Cardiac Remodeling: Findings in Mice Lacking Beta-carotene 9′,10′-oxygenase (BCO2) (FS06-04-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Chelsee Holloway ◽  
You-Kyung Kim ◽  
Loredana Quadro
Keyword(s):  
Vitamin A ◽  
Cardiac Hypertrophy ◽  
Mrna Expression ◽  
Active Form ◽  
Beta Carotene ◽  
Regulatory Genes ◽  
Chow Diet ◽  
Mrna Levels ◽  
Β Carotene

Abstract Objectives High intake of fruits and vegetables, main vitamin A sources, is associated with improved cardiac function. β-carotene, the most abundant dietary precursor of vitamin A, is cleaved by β-carotene 15,15′-oxygenase (BCO1) and β-carotene 9′,10′-oxygenase (BCO2). However, BCO2 is the only β-carotene cleavage enzyme expressed in adult hearts. Cardiac mRNA levels of Bco2 are elevated at mid-gestation in wild-type (WT) mice when the heart is hypertrophic. In the absence of BCO2 (Bco2-/- mice) the maternal heart fails to enlarge. Therefore, we aim to elucidate the role of BCO2 in maternal cardiac hypertrophy and to determine if metabolic pathways in the heart are disrupted by loss of BCO2. We hypothesize that BCO2 contributes to maternal cardiac hypertrophy by affecting homeostasis of RA, the active form of vitamin A. Methods Age matched WT and Bco2-/- (KO) mice raised on a chow diet were sacrificed at 14.5 days pregnant. Cardiac mRNA and protein expression of retinoid and lipid regulatory genes were measured. HPLC and LC/MS detected cardiac retinoids (vitamin A and its derivatives) levels. Results Pregnancy (mid-gestation) is associated with cardiac RA deficiency in WT dams. KO mice already showed cardiac RA deficiency pre-pregnancy. KO female mice have reduced PDK4 mRNA expression and enhanced PDH activity (phosphorylation) in the heart, that is reversed earlier, at mid-gestation. KO mice have increased cardiac Glut1 mRNA expression and reduced triglyceride levels. Lipid regulatory genes such as Pgc1a and Scd1 are increased at mid-pregnancy in the heart of WT dams but not in KO mothers. Conclusions Our data indicates that RA may be involved in modulating the cardiac hypertrophy of pregnancy. Dysregulation of RA homeostasis in the heart of KO females results in metabolic adaptations that makes the heart of the non-pregnant females preferentially dependent on glucose as an energy source. During pregnancy retinoic deficiency in the KO heart may induce an earlier attenuation of PDH activity, facilitating utilization of fat over glucose as energy substrate. These and other findings support the hypothesis of a crucial role of BCO2 in regulating heart hypertrophy, at least in females. Funding Sources NIH/NHLBI F31.

Dyrk1A-ASF-CaMKIIδ Signaling Is Involved in Valsartan Inhibition of Cardiac Hypertrophy in Renovascular Hypertensive Rats

Cardiology ◽  
2015 ◽  
Vol 133 (3) ◽  
pp. 198-204 ◽  
Author(s):  
Jian Yao ◽  
Xiaotong Qin ◽  
Jianhua Zhu ◽  
Hongzhuan Sheng
Keyword(s):  
Alternative Splicing ◽  
Cardiac Hypertrophy ◽  
Protein Expression ◽  
Mrna Expression ◽  
Systolic Function ◽  
Left Ventricular ◽  
Parameter Analysis ◽  
Hypertensive Rats ◽  
Dual Specificity ◽  
Dependent Protein

Objectives: It is known that the expression, activity and alternative splicing of Ca2+/calmodulin-dependent protein kinase IIδ (CaMKIIδ) are dysregulated in the cardiac remodeling process. Recently, we found a further signaling pathway, by which dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) regulates the alternative splicing of CaMKIIδ via the alternative splicing factor (ASF), i.e. Dyrk1A-ASF-CaMKIIδ. In this study, we aimed to investigate whether Dyrk1A-ASF-CaMKIIδ signaling was involved in valsartan inhibition of cardiac hypertrophy in renovascular hypertensive rats. Methods: Rats were subjected to two kidney-one clip (2K1C) surgery and then treated with valsartan (30 mg/kg/day) for 8 weeks. Hypertrophic parameter analysis was then performed. Western blot analysis was used to determine the protein expression of Dyrk1A and ASF and RT-PCR was used to analyze the alternative splicing of CaMKIIδ in the left ventricular (LV) sample. Results: Valsartan attenuated cardiac hypertrophy in 2K1C rats but without impairment of cardiac systolic function. Increased protein expression of Dyrk1A and decreased protein expression of ASF were observed in the LV sample of 2K1C rats. Treatment of 2K1C rats with valsartan reversed the changes in Dyrk1A and ASF expression in the LV sample. Valsartan adjusted the 2K1C-induced imbalance in alternative splicing of CaMKIIδ by upregulating the mRNA expression of CaMKIIδC and downregulating the mRNA expression of CaMKIIδA and CaMKIIδB. Conclusions: Valsartan inhibition of cardiac hypertrophy in renovascular hypertensive rats was mediated, at least partly, by Dyrk1A-ASF-CaMKIIδ signaling.

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