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Cardiac hypertrophy

Joseph B Fisher, Audrey Horst, Tina Wan, Min-Su Kim, John Auchampach, John Lough
Tat-interactive protein 60 (Tip60), encoded by the Kat5 gene, is a member of the MYST family of acetyltransferases. Cancer biology studies have shown that Tip60 induces the DNA damage response, apoptosis, and cell-cycle inhibition. Although Tip60 is expressed in the myocardium, its role in cardiomyocytes (CMs) is unclear. Earlier studies here showed that application of cardiac stress to globally targeted Kat5+/-haploinsufficient mice resulted in inhibition of apoptosis and activation of the CM cell-cycle, despite only modest reduction of Tip60 protein levels...
2016: PloS One
Arne O Melleby, Mari E Strand, Andreas Romaine, Kate M Herum, Biljana Skrbic, Christen P Dahl, Ivar Sjaastad, Arnt E Fiane, Jorge Filmus, Geir Christensen, Ida G Lunde
Pressure overload is a frequent cause of heart failure. Heart failure affects millions of patients worldwide and is a major cause of morbidity and mortality. Cell surface proteoglycans are emerging as molecular players in cardiac remodeling, and increased knowledge about their regulation and function is needed for improved understanding of cardiac pathogenesis. Here we investigated glypicans (GPC1-6), a family of evolutionary conserved heparan sulfate proteoglycans anchored to the extracellular leaflet of the cell membrane, in experimental and clinical heart failure, and explored the function of glypican-6 in cardiac cells in vitro...
2016: PloS One
Irfan Sahin, Baris Gungor, Berk Ozkaynak, Fatih Uzun, Suat Hayri Küçük, Ilhan Iker Avci, Ender Ozal, Burak Ayça, Sukru Cetın, Ertugrul Okuyan, Mustafa Hakan Dinckal
BACKGROUND: Correlation of increased copeptin levels with various cardiovascular diseases has been described. The clinical use of copeptin levels in patients with hypertrophic cardiomyopathy (HCM) has not been investigated before. HYPOTHESIS: In this study, we aimed to investigate the prognostic value of copeptin levels in patients with hypertrophic cardiomyopathy (HCM). METHODS: HCM was defined as presence of left ventricular wall thickness ≥15 mm in a subject without any concomitant disease that may cause left ventricular hypertrophy...
October 21, 2016: Clinical Cardiology
Alexander Bernt, Ashraf Y Rangrez, Matthias Eden, Andreas Jungmann, Sylvia Katz, Claudia Rohr, Oliver J Müller, Hugo A Katus, Samuel T Sossalla, Tatjana Williams, Oliver Ritter, Derk Frank, Norbert Frey
The objective of this study was to identify unknown modulators of Calcineurin (Cn)-NFAT signaling. Measurement of NFAT reporter driven luciferase activity was therefore utilized to screen a human cardiac cDNA-library (~10(7) primary clones) in C2C12 cells through serial dilutions until single clones could be identified. This extensive screening strategy culminated in the identification of SUMO2 as a most efficient Cn-NFAT activator. SUMO2-mediated activation of Cn-NFAT signaling in cardiomyocytes translated into a hypertrophic phenotype...
October 21, 2016: Scientific Reports
Vikrant Rai, Poonam Sharma, Swati Agrawal, Devendra K Agrawal
Heart disease causing cardiac cell death due to ischemia-reperfusion injury is a major cause of morbidity and mortality in the United States. Coronary heart disease and cardiomyopathies are the major cause for congestive heart failure, and thrombosis of the coronary arteries is the most common cause of myocardial infarction. Cardiac injury is followed by post-injury cardiac remodeling or fibrosis. Cardiac fibrosis is characterized by net accumulation of extracellular matrix proteins in the cardiac interstitium and results in both systolic and diastolic dysfunctions...
October 20, 2016: Molecular and Cellular Biochemistry
Xianxiu Wan, Jian-Jun Wen, Sue-Jie Koo, Lisa Yi Liang, Nisha Jain Garg
Chronic chagasic cardiomyopathy (CCM) is presented by increased oxidative/inflammatory stress and decreased mitochondrial bioenergetics. SIRT1 senses the redox changes and integrates mitochondrial metabolism and inflammation; and SIRT1 deficiency may be a major determinant in CCM. To test this, C57BL/6 mice were infected with Trypanosoma cruzi (Tc), treated with SIRT1 agonists (resveratrol or SRT1720), and monitored during chronic phase (~150 days post-infection). Resveratrol treatment was partially beneficial in controlling the pathologic processes in Chagas disease...
October 2016: PLoS Pathogens
Ruijie Liu, Hadi Khalil, Suh-Chin J Lin, Michelle A Sargent, Allen J York, Jeffery D Molkentin
Nemo-like kinase (NLK) is an evolutionary conserved serine/threonine protein kinase implicated in development, proliferation and apoptosis regulation. Here we identified NLK as a gene product induced in the hearts of mice subjected to pressure overload or myocardial infarction injury, suggesting a potential regulatory role with pathological stimulation to this organ. To examine the potential functional consequences of increased NLK levels, cardiac-specific transgenic mice with inducible expression of this gene product were generated, as well as cardiac-specific Nlk gene-deleted mice...
2016: PloS One
Elizabeth J Bhoj, Zhenming Yu, Qiaoning Guan, Rebecca Ahrens-Nicklas, Kajia Cao, Minjie Luo, Tanya Tischler, Matthew A Deardorff, Elaine Zackai, Avni B Santani
INTRODUCTION: RASopathies include disorders generally characterized by developmental delay, specific heart defects, short stature, cardiac hypertrophy, and facial dysmorphisms. Next-generation sequencing (NGS)-based panels have widespread acceptance as a diagnostic tool for RASopathies. MATERIALS AND METHODS: The first 126 patients evaluated by clinical examination and the NGS RASopathy panel at the Children's Hospital of Philadelphia were enrolled. We calculated diagnosis rate, correlated reported clinical findings with positive or negative test results, and identified final molecular diagnoses in 28/96 patients who tested negative for RASopathies...
October 20, 2016: Genetics in Medicine: Official Journal of the American College of Medical Genetics
Rosita Zakeri, Gilles Moulay, Qiang Chai, Ozgur Ogut, Saad Hussain, Hiroyuki Takahama, Tong Lu, Xiao-Li Wang, Wolfgang A Linke, Hon-Chi Lee, Margaret M Redfield
BACKGROUND: Left atrial (LA) compliance and contractility influence left ventricular stroke volume. We hypothesized that diminished LA compliance and contractile function occur early during the development of heart failure with preserved ejection fraction (HFpEF) and impair overall cardiac performance. METHODS AND RESULTS: Cardiac magnetic resonance imaging, echocardiography, left ventricular and LA pressure-volume studies, and tissue analyses were performed in a model of early HFpEF (elderly dogs, renal wrap-induced hypertension, exogenous aldosterone; n=9) and young control dogs (sham surgery; n=13)...
October 2016: Circulation. Heart Failure
Catarina Francisco, João Sérgio Neves, Inês Falcão-Pires, Adelino Leite-Moreira
Adiponectin is the most abundant adipokine and exhibits anti-inflammatory, antiatherogenic and antidiabetic properties. Unlike other adipokines, it inversely correlates with body weight and obesity-linked cardiovascular complications. Diastolic dysfunction is the main mechanism responsible for approximately half of all heart failure cases, the so-called heart failure with preserved ejection fraction (HFpEF), but therapeutic strategies specifically directed towards these patients are still lacking. In the last years, a link between adiponectin and diastolic dysfunction has been suggested...
October 18, 2016: Cardiovascular Drugs and Therapy
Attila Oláh, Dalma Kellermayer, Csaba Mátyás, Balázs Tamás Németh, Árpád Lux, Lilla Szabó, Marianna Török, Mihály Ruppert, Anna Meltzer, Alex Ali Sayour, Kálmán Benke, István Hartyánszky, Béla Merkely, Tamás Radovits
PURPOSE: Long-term exercise training is associated with characteristic cardiac adaptation, termed athlete's heart. Our research group previously characterized in vivo left ventricular (LV) function of exercise-induced cardiac hypertrophy in detail in a rat model, however the effect of detraining on LV function is still unclear. We aimed at evaluating the reversibility of functional alterations of athlete's heart after detraining. METHODS: Rats (n=16) were divided into detrained exercised (DEx) and detrained control (DCo) groups...
October 14, 2016: Medicine and Science in Sports and Exercise
Yuichi Takashi, Yuka Kinoshita, Michiko Hori, Nobuaki Ito, Manabu Taguchi, Seiji Fukumoto
PURPOSE: Fibroblast growth factor 23 (FGF23) is a hormone regulating phosphate metabolism. Excessive actions of FGF23 cause several types of FGF23-related hypophosphatemic rickets/osteomalacia. Recently, it was reported that FGF23 levels were independently correlated with left ventricular hypertrophy (LVH) in patients with chronic kidney disease (CKD). In addition, FGF23 was also shown to cause cardiac hypertrophy directly acting on cardiomyocytes. However, there is no study indicating the correlation between FGF23 and LVH in adult patients with FGF23-related hypophosphatemic rickets/osteomalacia...
October 18, 2016: Endocrine Research
Svetlana Villevalde, Zhanna Kovbalava
OBJECTIVE: Microalbuminuria (MAU) and glomerular filtration rate (GFR) are the signs of subclinical kidney damage, independently predict cardiovascular morbidity and mortality. The aim of the study was to investigate the relative role of MAU, cardiac and vascular ultrasonography, carotid-femoral pulse wave velocity (PWV) for the detection of hypertensive target organ damage (TOD) and risk stratification. DESIGN AND METHOD: In 576 non-diabetic hypertensive patients without established cardiovascular or renal disease (291 male, 53...
September 2016: Journal of Hypertension
Trefor Morgan
Central Systolic Blood Pressure is lower than brachial artery blood Pressure due to reflected waves and greater augmentation at the periphery. The relationship is not consistent during life and alters with aging of the blood vessels. Increasing stiffness means that a greater component of the reflected waves returns to the central aorta during systolic contraction causing more amplification and a higher systolic blood pressure. Diastolic blood pressure on the other hand is always higher in the aorta than at the periphery allowing blood flow...
September 2016: Journal of Hypertension
Qiongying Wang, Peng Chang, Han Xu, Feng Bai, Jing Yu
OBJECTIVE: Hypertension induced hypertrophy and diastolic dysfunction and is associated with cardiac oxidation and reduced NO production. We hypothesized that tetrahydrobiopterin (BH4) can regulate the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway and reverse cardiac hypertrophy and diastolic dysfunction in spontaneously hypertensive rats. DESIGN AND METHOD: Ten-week-old male spontaneously hypertensive rats (SHR) and age-matched normotensive control Wistar-Kyoto (WKY) rats were divided into five groups, WKY,WKY + BH4, SHR, SHR + BH4 and SHR + VAL...
September 2016: Journal of Hypertension
Sheila Patel, Elena Velkoska, Louise Burrell
OBJECTIVE: Left ventricular hypertrophy (LVH) is prevalent in chronic kidney disease (CKD) and a major cause of cardiovascular morbidity and mortality. Treatment of LVH in CKD is based on blood pressure control. The Kruppel like factor 15 (KLF15) is expressed in the heart and acts as a repressor of cardiac hypertrophy and fibrosis. The role of cardiac KLF15 in the development of LVH in rats with CKD secondary to subtotal nephrectomy (STNx) or the effects of ACE inhibition on KLF15 levels has not been addressed previously...
September 2016: Journal of Hypertension
Tomonori Sugiura, Hiroyuki Takase, Shunsuke Murai, Sumiyo Yamashiya, Nobuyuki Ohte, Yasuaki Dohi
OBJECTIVE: The heart is one of the target organs of hypertension. Cardiac muscle responds to an increase in afterload by developing hypertrophy. In the process of developing hypertension, the heart is exposed to a transiently, but frequent, increase in afterload. The present study was designed to test the hypothesis that left ventricular hypertrophy assessed by electrocardiography (ECG) predicts future development of hypertension. DESIGN AND METHOD: Normotensive subjects who visited our hospital for a physical check-up (n = 5770; age, 52...
September 2016: Journal of Hypertension
Manan Pareek, Mette Lundgren Nielsen, Margrét Leósdóttir, Peter M Nilsson, Michael Hecht Olsen
OBJECTIVE: To explore the independent prognostic value of left ventricular (LV) mass, diastolic function, and fasting plasma glucose (FPG) for the prediction of incident cardiac events in a random population sample. DESIGN AND METHOD: 415 women and 999 men aged 56-79 years, included between 2002-2006, underwent echocardiography based on groups defined by FPG, i.e. normal (NFG): FPG ≤ 6.0 mmol/L; impaired (IFG): FPG 6.1-6.9 mmol/L; and diabetes mellitus (DM): FPG ≥ 7...
September 2016: Journal of Hypertension
Hyun Ju Yoon
OBJECTIVE: The aim of this study was to investigate the impact of diastolic functional recovery on pre-discharge echocardiography on future adverse events in the patients with hypertensive heart failure (HHF). DESIGN AND METHOD: A total of 136 hospitalized patients with HHF were divided into 2 groups according to the change of diastolic function on pre-discharge echocardiography; the improving group (n = 65, 47.9 ± 14.4years, 49 males) vs non-improving group (n = 71, 52...
September 2016: Journal of Hypertension
Koki Takane, Yu Hasegawa, Lin Bowen, Takashi Yokoo, Shokei Kim-Mitsuyama
OBJECTIVE: Increasing evidences suggest that patients with Alzheimer's disease (AD) show not only cognitive impairment but also physical disorder including cardiac dysfunction and sarcopenia. In this study, we investigated whether central angiotensin II, inducer of oxidative stress, led to the organ dysfunction in a mouse model of AD. DESIGN AND METHOD: 5XFAD which is an animal model of AD and C57BL/6 (WT) were each assigned to 1) normal saline and 2) angiotensin II (20 mg/kg/h) groups...
September 2016: Journal of Hypertension
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