Pubblicazioni recenti - cardiac hypertrophy

• Adenosine A receptor activation prevents DOCA-salt induced hypertensive cardiac remodeling via iBAT.
  Biochem Biophys Res Commun

  2020 Feb;():. doi: S0006-291X(20)30301-6.
  
  Zhou Yan-Ping, Ruan Cheng-Chao, Kong Ling-Ran, Gao Ping-Jin,
  
  Abstract
  
  Hypertensive cardiac remodeling is a constellation of abnormalities that includes cardiomyocyte hypertrophy and death and tissue fibrosis. Adenosine is a long-known vasodilator, through interacting with its four cell surface receptor subtypes in cardiovascular system. However, it is unclear that whether adenosine A receptor (AR) activation is involved in the cardiac remodeling in hypertension. WT mice were utilized to induce DOCA-salt sensitive hypertension and received AR agonist CGS21680 or antagonist KW6002 treatment. Cardiac functional phenotyping measurement by echocardiography showed that CGS21680 improved cardiac dysfunction in DOCA-salt mice. Moreover, CGS21680 reduced cardiomyocyte hypertrophy, cardiac inflammation and fibrosis. However, iBAT depletion surgery induces dramatic cardiac remodeling in DOCA-salt mice, and the protective function of CGS21680 was blocked without intact iBAT. Mechanistically, AR agonist CGS21680 increased iBAT-derived fibroblast growth factor 21 (FGF21). Our data suggest that activation of AR could be a potential therapeutic strategy in preventing heart damage in hypertension.
  
  Copyright © 2020 Elsevier Inc. All rights reserved.
  
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• LncRNA AK045171 protects the heart from cardiac hypertrophy by regulating the SP1/MG53 signalling pathway.
  Aging (Albany NY)

  2020 Feb;12():. doi: 10.18632/aging.102668.
  
  Xu Li, Wang Hongjiang, Jiang Feng, Sun Hao, Zhang Dapeng,
  
  Abstract
  
  Hearts often undergo abnormal remodelling and hypertrophic growth in response to pathological stress. Long non-coding RNAs (LncRNAs) can change cardiac function and participate in regulation of cardiac hypertrophy. The present study aims to identify the role of AK045171 in cardiac hypertrophy and the underlying mechanism in hypertrophic cascades. Mice with cardiac hypertrophy were established through transverse aortic constriction (TAC). Cardiac hypertrophy in cardiomyocytes was induced by angiotensin II (angII). The expression of AK045171 and its target gene SP1 was examined in cardiomyocytes transfected with miRNA. The AK045171 expression level was downregulated in mice after TAC surgery. Overexpression of AK045171 attenuated cardiac hypertrophy both in vitro and in vivo. The mechanism study indicated that AK045171 binds with SP1, which promotes transcription activation of MEG3. It is suggested that overexpression of AK045171 might have clinical potential to suppress cardiac hypertrophy and heart failure.
  
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• Suppression of store-operated calcium entry causes dilated cardiomyopathy of the heart.
  Biol Open

  2020 Feb;():. doi: bio.049999.
  
  Petersen Courtney E, Wolf Matthew J, Smyth Jeremy T,
  
  Abstract
  
  Store-operated Ca entry (SOCE) is an essential Ca signaling mechanism present in most animal cells. SOCE refers to Ca influx that is activated by depletion of sarco/endoplasmic reticulum (S/ER) Ca stores. The main components of SOCE are STIM and Orai. STIM proteins function as S/ER Ca sensors, and upon S/ER Ca depletion STIM rearranges to S/ER-plasma membrane junctions and activates Orai Ca influx channels. Studies have implicated SOCE in cardiac hypertrophy pathogenesis, but SOCE's role in normal heart physiology remains poorly understood. We therefore analyzed heart-specific SOCE function in , a powerful animal model of cardiac physiology. We show that heart-specific suppression of and in larvae and adults resulted in reduced contractility consistent with dilated cardiomyopathy. Myofibers were also highly disorganized in and RNAi hearts, reflecting possible decompensation or upregulated stress signaling. Furthermore, we show that reduced heart function due to SOCE suppression adversely affected animal viability, as heart specific and RNAi animals exhibited significant delays in post-embryonic development and adults died earlier than controls. Collectively, our results demonstrate that SOCE is essential for physiological heart function, and establish as an important model for understanding the role of SOCE in cardiac pathophysiology.
  
  © 2020. Published by The Company of Biologists Ltd.
  
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• Cardiac-specific inactivation of effects cardiac conduction abnormalities and cardiomyopathy-associated phenotypes.
  Am J Physiol Heart Circ Physiol

  2020 Feb;():. doi: 10.1152/ajpheart.00647.2019.
  
  Nam Jeong Min, Lim Ji Eun, Ha Tae Woong, Oh Bermseok, Kang Ji-One,
  
  Abstract
  
  A variant in the locus has been correlated with QRS duration in an electrocardiogram genomewide association study, and the deletion of has been implicated as a causal factor of the dilated cardiomyopathy that is linked to 1p36 deletion syndrome. We aimed to determine how a null mutation of affects cardiac function and study the underlying mechanism of the resulting phenotype in an appropriate mouse model. We used cardiac-specific conditional knockout mice to examine cardiac function by electrocardiography. QRS duration and QTc interval increased significantly in cardiac-specific knockout animals compared with wild-type mice. Further, we assessed cardiomyopathy-associated features by trichrome staining, densitometry, and hydroxyproline assay. -null hearts showed greater fibrosis and cardiomyocyte hypertrophy. By quantitative real-time PCR, -null hearts upregulated extracellular matrix-related genes (, ) and a-smooth muscle actin (), a myofibroblast marker. Moreover, TGF-b signaling was activated in -null hearts, as evidenced by increased transcript levels and phosphorylated Smad2. However, the inhibition of TGF-b receptor did not reverse the aberrations in conduction in cardiac-specific knockout mice. To determine the underlying mechanisms, we performed RNA-seq using mouse left ventricular tissue. By functional analysis, -null hearts experienced dysregulated expression of ion channel genes, including , , , and . Mice with -null hearts develop abnormalities in cardiac conduction and cardiomyopathy-associated phenotypes, including fibrosis and cellular hypertrophy. Further, the RNA-seq findings suggest that impairments in ion homeostasis (Ca, K, and Na) may at least partially underlie the abnormal conduction in cardiac-specific knockout mice.
  
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• Autonomic dysfunction in cardiac amyloidosis assessed by heart rate variability and heart rate turbulence.
  Ann Noninvasive Electrocardiol

  2020 Feb;():e12749. doi: 10.1111/anec.12749.
  
  Yamada Shinya, Yoshihisa Akiomi, Hijioka Naoko, Kamioka Masashi, Kaneshiro Takashi, Yokokawa Tetsuro, Misaka Tomofumi, Ishida Takafumi, Takeishi Yasuchika,
  
  Abstract
  
  BACKGROUND:
  Cardiac amyloidosis (CA) is characterized by left ventricular hypertrophy (LVH) and autonomic nervous imbalance due to amyloid infiltration. However, autonomic dysfunction is often seen in heart failure (HF) with LVH from other etiologies. We aimed to characterize autonomic dysfunction in CA from other etiologies of LVH.
  
  METHODS:
  Fifty-five HF patients with LVH (35 males, mean age 65 ± 16 years) were enrolled. LVH was defined as left ventricular mass index measured by echocardiography >95 g/m in women and 115 g/m in men. The etiology was as follows: amyloid light chain (AL)-CA, n = 14; hypertrophic cardiomyopathy, n = 21; and aortic stenosis (AS), n = 20. With the patient in a clinically stable condition, heart rate variability (HRV) and heart rate turbulence (HRT), which reflect autonomic dysfunction, were measured using Holter monitoring and compared among the three groups.
  
  RESULTS:
  Brain natriuretic peptide levels, LVH severity, left ventricular ejection fraction, and tissue Doppler index E/e' did not differ among the three groups. However, severe abnormalities of HRV and HRT were obtained in AL-CA. In the ROC analysis to identify AL-CA in HF with LVH, the best cutoff value for standard deviation of all R-R intervals, standard deviation of the 5-min mean R-R intervals, turbulence onset, and turbulence slope were 68.5 ms (AUC: 0.865), 58.5 ms (AUC: 0.834), 0.25% (AUC: 0.813), and 1.00 ms/RR (AUC 0.736), respectively.
  
  CONCLUSION:
  Autonomic dysfunction is a hallmark of AL-CA, and its noninvasive assessment by Holter monitoring may be a useful tool for differential diagnosis of HF with LVH.
  
  © 2020 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals, Inc.
  
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• Mechanical Regulation of Protein Translation in the Cardiovascular System.
  Front Cell Dev Biol

  2020 ;8():34. doi: 10.3389/fcell.2020.00034.
  
  Simpson Lisa J, Reader John S, Tzima Ellie,
  
  Abstract
  
  The cardiovascular system can sense and adapt to changes in mechanical stimuli by remodeling the physical properties of the heart and blood vessels in order to maintain homeostasis. Imbalances in mechanical forces and/or impaired sensing are now not only implicated but are, in some cases, considered to be drivers for the development and progression of cardiovascular disease. There is now growing evidence to highlight the role of mechanical forces in the regulation of protein translation pathways. The canonical mechanism of protein synthesis typically involves transcription and translation. Protein translation occurs globally throughout the cell to maintain general function but localized protein synthesis allows for precise spatiotemporal control of protein translation. This Review will cover studies on the role of biomechanical stress -induced translational control in the heart (often in the context of physiological and pathological hypertrophy). We will also discuss the much less studied effects of mechanical forces in regulating protein translation in the vasculature. Understanding how the mechanical environment influences protein translational mechanisms in the cardiovascular system, will help to inform disease pathogenesis and potential areas of therapeutic intervention.
  
  Copyright © 2020 Simpson, Reader and Tzima.
  
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• Fruit Rich in Polyphenols Attenuates Isoproterenol-Induced Cardiac Hypertrophy in Rats via Inhibition of Inflammation and Oxidative Stress.
  Oxid Med Cell Longev

  2020 ;2020():7147498. doi: 10.1155/2020/7147498.
  
  Kumari Sima, Katare Parmeshwar B, Elancheran R, Nizami Hina L, Paramesha Bugga, Arava Sudheer, Sarma Partha Pratim, Kumar Roshan, Mahajan Dinesh, Kumar Yashwant, Devi Rajlakshmi, Banerjee Sanjay K,
  
  Abstract
  
  Colla (Family: Musaceae), commonly known as banana and native to India and other parts of Asia, is very rich in nutritional value and has strong antioxidant potential. In the present study, we have developed (MB) fruit pulp powder and evaluated its cardioprotective effect in cardiac hypertrophy, which is often associated with inflammation and oxidative stress. An ultra-high-pressure liquid chromatography-mass spectrometer (UPLC-MS/MS) has been used for the detection and systematic characterization of the phenolic compounds present in fruit pulp. The cardioprotective effect of MB was evaluated in a rat model of isoproterenol- (ISO-) induced cardiac hypertrophy by subcutaneous administration of isoproterenol (5?mg/kg/day), delivered through an alzet minipump for 14 days. Oral administration of MB fruit pulp powder (200?mg/kg/day) significantly ( < 0.001) decreased heart weight/tail length ratio and cardiac hypertrophy markers like ANP, BNP, -MHC, and collagen-1 gene expression. MB also attenuated ISO-induced cardiac inflammation and oxidative stress. The data were further confirmed in H9c2 cells where the antihypertrophic and anti-inflammatory effect of the aqueous extract of MB was observed in the presence of ISO and lipopolysaccharide (LPS), respectively. This study strongly suggests that supplementation of dried fruit powder can be useful for the prevention of cardiac hypertrophy via the inhibition of inflammation and oxidative stress.
  
  Copyright © 2020 Sima Kumari et al.
  
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• Assessment of Short-term, Within Hospital Cardiovascular Complications After Renal Transplantation in Baqiyatallah Hospital.
  Mater Sociomed

  2019 Dec;31(4):241-245. doi: 10.5455/msm.2019.31.241-245.
  
  Ghahrodi Mohsen Sadeghi, Einollahi Behzad, Baharvand Amir, Javanbakht Mohammad,
  
  Abstract
  
  Introduction:
  Several studies have looked at cardiac complications in patients with end-stage renal disease (ESRD) after renal transplantation, but more attention has been paid to the long-term cardiovascular complications.
  
  Aim:
  The present study was designed to investigate the short-term cardiovascular complications of intrahospital hospitalization in post-renal transplant patients and related factors.
  
  Methods:
  In this retrospective cohort study, the medical records of all renal transplant patients in Baqiyatallah Hospital between 2015 and 2018 during the post-transplantation phase were investigated. Demographic data, transplantation type, cardiac risk factors, pre-operation cardiac consultation and para-clinical tests results were extracted from the patients' records. The frequency and factors influencing the need for re-visitation as well as its final diagnosis were analyzed.
  
  Results:
  A total of 982 patients with a mean age of 13.73 ± 45.33 years were studied (62.6% males). In 39.8% of patients, cardiology re-visitation was required; of these 391 visits, only 162 patients (41.4%) had heart problems. In multivariate analysis, patients' need for cardiac reconsideration was predicted by 7 variables; age, diabetes, history of CABG, ECG, echocardiography, angiography, and myocardial perfusion scan (R = 0.652, P <0.001). Furthermore, the five variables of first cardiology consultant, the first consultation physician, left ventricular hypertrophy, having history of angiography and myocardial perfusion scan, can predict the final diagnosis of cardiac problems in re-counseling (R = 0.188, P = 0.043).
  
  Conclusion:
  Given the high prevalence of need for a patient's recurrent cardiac visit, it seems that risk assessment prior to kidney transplantation needs to be more accurate. It is recommended that elderly patients with abnormal findings in electrocardiography and echocardiography, having diabetes, having a history of negative coronary angiography or myocardial perfusion scan be more closely monitored for heart disease.
  
  © 2019 Mohsen Sadeghi Ghahrodi, Behzad Einollahi, Amir Baharvand, Mohammad Javanbakht.
  
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• Detection of Hypertrophic Cardiomyopathy Using a Convolutional Neural Network-Enabled Electrocardiogram.
  J Am Coll Cardiol

  2020 Feb;75(7):722-733. doi: S0735-1097(20)30003-6.
  
  Ko Wei-Yin, Siontis Konstantinos C, Attia Zachi I, Carter Rickey E, Kapa Suraj, Ommen Steve R, Demuth Steven J, Ackerman Michael J, Gersh Bernard J, Arruda-Olson Adelaide M, Geske Jeffrey B, Asirvatham Samuel J, Lopez-Jimenez Francisco, Nishimura Rick A, Friedman Paul A, Noseworthy Peter A,
  
  Abstract
  
  BACKGROUND:
  Hypertrophic cardiomyopathy (HCM) is an uncommon but important cause of sudden cardiac death.
  
  OBJECTIVES:
  This study sought to develop an artificial intelligence approach for the detection of HCM based on 12-lead electrocardiography (ECG).
  
  METHODS:
  A convolutional neural network (CNN) was trained and validated using digital 12-lead ECG from 2,448 patients with a verified HCM diagnosis and 51,153 non-HCM age- and sex-matched control subjects. The ability of the CNN to detect HCM was then tested on a different dataset of 612 HCM and 12,788 control subjects.
  
  RESULTS:
  In the combined datasets, mean age was 54.8 ± 15.9 years for the HCM group and 57.5 ± 15.5 years for the control group. After training and validation, the area under the curve (AUC) of the CNN in the validation dataset was 0.95 (95% confidence interval [CI]: 0.94 to 0.97) at the optimal probability threshold of 11% for having HCM. When applying this probability threshold to the testing dataset, the CNN's AUC was 0.96 (95% CI: 0.95 to 0.96) with sensitivity 87% and specificity 90%. In subgroup analyses, the AUC was 0.95 (95% CI: 0.94 to 0.97) among patients with left ventricular hypertrophy by ECG criteria and 0.95 (95% CI: 0.90 to 1.00) among patients with a normal ECG. The model performed particularly well in younger patients (sensitivity 95%, specificity 92%). In patients with HCM with and without sarcomeric mutations, the model-derived median probabilities for having HCM were 97% and 96%, respectively.
  
  CONCLUSIONS:
  ECG-based detection of HCM by an artificial intelligence algorithm can be achieved with high diagnostic performance, particularly in younger patients. This model requires further refinement and external validation, but it may hold promise for HCM screening.
  
  Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
  
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• Concurrent thoracic pathology identified with radiology in hyperthyroid cats referred for radioiodine therapy.
  J Feline Med Surg

  2020 Feb;():1098612X19900408. doi: 10.1177/1098612X19900408.
  
  Kormpou Foteini, Gil-Morales Claudia, Warren-Smith Chris, Hibbert Angie,
  
  Abstract
  
  OBJECTIVES:
  Radioiodine (RAI) treatment for hyperthyroidism is becoming increasingly available in the UK. Pretreatment assessment is commonly performed, as patient handling is limited once RAI has been administered. The aims of this study were to determine the prevalence of thoracic pathology using thoracic radiography in hyperthyroid cats referred for RAI treatment and to determine the value of this technique pretreatment.
  
  METHODS:
  The hospital databases were searched for hyperthyroid cats referred for RAI treatment at the Feline Centre, Langford Vets, between January 2012 and July 2016. Radiographs were reviewed by Diplomates of the European College of Veterinary Diagnostic Imaging at the time of treatment and each set of radiographs was subsequently reviewed by one radiologist for the study. Cardiorespiratory signs were recorded, if present, and any change in treatment plan or suitability for RAI treatment was documented.
  
  RESULTS:
  Two hundred and fifty-two cats were included in the study. Thoracic pathology was identified in 77% (n?=?194/252) of the cats, of which 59% (n?=?115/194) had pulmonary abnormalities with bronchial and bronchointerstitial patterns most frequently; 57% (n?=?111/194) had skeletal abnormalities and 43% (n?=?84/194) had cardiac abnormalities, with mild-to-moderate cardiomegaly most prevalent. Other abnormalities included sternal lymphadenomegaly (7%; n?=?13/194), mediastinal pathology (3%; n?=?5/194), oesophageal pathology (2%; n?=?4/194) and pleural space disease (0.5%; n?=?1/194).Twelve cases (6%) had a change in their treatment plan as a result of thoracic radiographic abnormalities, of which five subsequently underwent RAI treatment.
  
  CONCLUSIONS AND RELEVANCE:
  A low prevalence of significant thoracic pathology was identified on radiographs in hyperthyroid cats referred for RAI treatment. Incidental thoracic abnormalities were found much more commonly; hence, results of thoracic radiology need to be combined with the clinical picture, to decide whether further investigations or alterations to the treatment plan are required pre-RAI.
  
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• Myotubularin-related protein 14 suppresses cardiac hypertrophy by inhibiting Akt.
  Cell Death Dis

  2020 Feb;11(2):140. doi: 10.1038/s41419-020-2330-6.
  
  Zhang Jie-Lei, Zhang Dian-Hong, Li Ya-Peng, Wu Lei-Ming, Liang Cui, Yao Rui, Wang Zheng, Feng Sheng-Dong, Wang Zhong-Min, Zhang Yan-Zhou,
  
  Abstract
  
  Cardiac hypertrophy (CH) is an independent risk factor for many cardiovascular diseases, and is one of the primary causes of morbidity and mortality in elderly people. Pathological CH involves excessive protein synthesis, increased cardiomyocyte size, and ultimately the development of heart failure. Myotubularin-related protein 14 (MTMR14) is a member of the myotubularin (MTM)-related protein family, which is involved in apoptosis, aging, inflammation, and autophagy. However, its exact function in CH is still unclear. Herein, we investigated the roles of MTMR14 in CH. We show that MTMR14 expression was increased in hypertrophic mouse hearts. Mice deficient in heart MTMR14 exhibited an aggravated aortic-banding (AB)-induced CH phenotype. In contrast, MTMR14 overexpression prevented pressure overload-induced hypertrophy. At the molecular level, prevention of CH in the absence of MTMR14 involved elevations in Akt pathway components, which are key elements that regulate apoptosis and cell proliferation. These results demonstrate that MTMR14 is a new molecular target for the treatment of CH.
  
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• A case report on transient global ventricular wall thickening secondary to acute myocarditis: Focus on the unique role of cardiac MRI.
  Medicine (Baltimore)

  2020 Feb;99(8):e19223. doi: 10.1097/MD.0000000000019223.
  
  Xu Tiantian, Hu Hongjie,
  
  Abstract
  
  INTRODUCTION:
  Transient left ventricular wall thickening is known to develop in the acute phase of myocarditis, with several reports documenting this unusual mode of myocarditis. Diagnosing myocarditis can be challenging because symptoms, clinical exam findings, electrocardiogram results, biomarkers, and echocardiogram results are often non-specific. Therefore, cardiac magnetic resonance imaging has become the primary non-invasive imaging tool in patients with suspected myocarditis.
  
  PATIENT CONCERNS AND DIAGNOSIS:
  A 51-year-old male was referred to our hospital with a 20-day history of fever. Initial echocardiogram demonstrated diffuse concentric left ventricular hypertrophy with depressed left ventricular diastolic function, previously misdiagnosed as restrictive cardiomyopathy. Cardiac magnetic resonance imaging (MRI) showed global ventricular wall thickening, and the negative delayed enhancement made hypertrophic cardiomyopathy and myocardial amyloidosis less likely. This information, along with laboratory analyses, led to a diagnosis of acute myocarditis.
  
  INTERVENTIONS AND OUTCOMES:
  The patient underwent a treatment regimen, including a prescription of levofloxacin and other supporting treatments. During the period following, the patient experienced a few minor episodes of atypical chest pain with spontaneous remission. The patient was discharged after 8 days of hospitalization. A cardiac MRI evaluation was repeated after 17 months, this time showing that the wall thickness had returned to normal; the myocarditis resolved without sequela.
  
  CONCLUSIONS:
  In summary, we report on a case of transient global ventricular wall thickening secondary to acute myocarditis, which rarely has been described previously. Our study demonstrates that transient ventricular wall thickening related to myocardial interstitial edema also can involve the right ventricular wall, a fact that is important in diagnosis and differential diagnosis. Cardiovascular magnetic resonance currently is considered the most comprehensive and accurate diagnostic tool in patients with suspected myocarditis.
  
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• TRPC Channels in Cardiac Plasticity.
  Cells

  2020 Feb;9(2):. doi: E454.
  
  Numaga-Tomita Takuro, Nishida Motohiro,
  
  Abstract
  
  The heart flexibly changes its structure in response to changing environments and oxygen/nutrition demands of the body. Increased and decreased mechanical loading induces hypertrophy and atrophy of cardiomyocytes, respectively. In physiological conditions, these structural changes of the heart are reversible. However, chronic stresses such as hypertension or cancer cachexia cause irreversible remodeling of the heart, leading to heart failure. Accumulating evidence indicates that calcium dyshomeostasis and aberrant reactive oxygen species production cause pathological heart remodeling. Canonical transient receptor potential (TRPC) is a nonselective cation channel subfamily whose multimodal activation or modulation of channel activity play important roles in a plethora of cellular physiology. Roles of TRPC channels in cardiac physiology have been reported in pathological cardiac remodeling. In this review, we summarize recent findings regarding the importance of TRPC channels in flexible cardiac remodeling (i.e., cardiac plasticity) in response to environmental stresses and discuss questions that should be addressed in the near future.
  
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• The Crosstalk between Cardiac Lipotoxicity and Mitochondrial Oxidative Stress in the Cardiac Alterations in Diet-Induced Obesity in Rats.
  Cells

  2020 Feb;9(2):. doi: E451.
  
  Jiménez-González Sara, Marín-Royo Gema, Jurado-López Raquel, Bartolomé María Visitación, Romero-Miranda Ana, Luaces María, Islas Fabián, Nieto María Luisa, Martínez-Martínez Ernesto, Cachofeiro Victoria,
  
  Abstract
  
  The impact of the mitochondria-targeted antioxidant MitoQ was evaluated in the cardiac alterations associated with obesity. Male Wistar rats were fed either a high fat diet (HFD, 35% fat) or a standard diet (CT, 3.5% fat) for 7 weeks and treated with MitoQ (200 µM). The effect of MitoQ (5 nM) in rat cardiac myoblasts treated for 24 h with palmitic acid (PA, 200 µM) was evaluated. MitoQ reduced cardiac oxidative stress and prevented the development of cardiac fibrosis, hypertrophy, myocardial -FDG uptake reduction, and mitochondrial lipid remodeling in HFD rats. It also ameliorated cardiac mitochondrial protein level changes observed in HFD: reductions in fumarate hydratase, complex I and II, as well as increases in mitofusin 1 (MFN1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha, and cyclophilin F (cycloF). In vitro, MitoQ prevented oxidative stress and ameliorated alterations in mitochondrial proteins observed in palmitic acid (PA)-stimulated cardiac myoblasts: increases in carnitine palmitoyltransferase 1A, cycloF, and cytochrome C. PA induced phosphorylation of extracellular signal-regulated kinases and nuclear factor-?B p65. Therefore, the data show the beneficial effects of MitoQ in the cardiac damage induced by obesity and suggests a crosstalk between lipotoxicity and mitochondrial oxidative stress in this damage.
  
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• Polyploidy in Cardiomyocytes: Roadblock to Heart Regeneration?
  Circ Res

  2020 Feb;126(4):552-565. doi: 10.1161/CIRCRESAHA.119.315408.
  
  Derks Wouter, Bergmann Olaf,
  
  Abstract
  
  The hallmark of most cardiac diseases is the progressive loss of cardiomyocytes. In the perinatal period, cardiomyocytes still proliferate, and the heart shows the capacity to regenerate upon injury. In the adult heart, however, the actual rate of cardiomyocyte renewal is too low to efficiently counteract substantial cell loss caused by cardiac injury. In mammals, cardiac growth by cell number expansion changes to growth by cardiomyocyte enlargement soon after birth, coinciding with a period in which most cardiomyocytes increase their DNA content by multinucleation and nuclear polyploidization. Although cardiomyocyte hypertrophy is often associated with these processes, whether polyploidy is a prerequisite or a consequence of hypertrophic growth is unclear. Both the benefits of cardiomyocyte enlargement over proliferative growth of the heart and the physiological role of polyploidy in cardiomyocytes are enigmatic. Interestingly, hearts in animal species with substantial cardiac regenerative capacity dominantly comprise diploid cardiomyocytes, raising the hypothesis that cardiomyocyte polyploidy poses a barrier for cardiomyocyte proliferation and subsequent heart regeneration. On the contrary, there is also evidence for self-duplication of multinucleated myocytes, suggesting a more complex picture of polyploidy in heart regeneration. Polyploidy is not restricted to the heart but also occurs in other cell types in the body. In this review, we explore the biological relevance of polyploidy in different species and tissues to acquire insight into its specific role in cardiomyocytes. Furthermore, we speculate about the physiological role of polyploidy in cardiomyocytes and how this might relate to renewal and regeneration.
  
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• Association of Urine Albumin/Creatinine Ratio below 30?mg/g and Left Ventricular Hypertrophy in Patients with Type 2 Diabetes.
  Biomed Res Int

  2020 ;2020():5240153. doi: 10.1155/2020/5240153.
  
  Xie Xiangkun, Peng Zhengliang, Li Hanlin, Li Dan, Tu Yan, Bai Yujia, Huang Xingfu, Lai Wenyan, Zhan Qiong, Zeng Qingchun, Xu Dingli,
  
  Abstract
  
  Several studies show that even a level of urine albumin/creatinine ratio (UACR) within the normal range (below 30?mg/g) increases the risk of cardiovascular diseases. We speculate that mildly increased UACR is related to left ventricular hypertrophy (LVH) in patients with type 2 diabetes mellitus (T2DM). In this retrospective study, 317 patients with diabetes with normal UACR, of whom 62 had LVH, were included. The associations between UACR and laboratory indicators, as well as LVH, were examined using multivariate linear regression and logistic regression, respectively. The diagnostic efficiency and the optimal cutoff point of UACR for LVH were evaluated using the area under the receiver operating characteristic curve (AUC) and Youden index. Our results showed that patients with LVH had significantly higher UACR than those without LVH ( < 0.001). The prevalence of LVH presented an upward trend with the elevation of UACR. UACR was independently and positively associated with hemoglobin A1c ( < 0.001). UACR can differentiate LVH (AUC?=?0.682, 95% CI (0.602-0.760), < 0.001). The optimal cutoff point determined with the Youden index was UACR?=?10.2?mg/g. When categorized by this cutoff point, the odds ratio (OR) for LVH in patients in the higher UACR group (10.2-30?mg/g) was 3.104 (95% CI: 1.557-6.188, =0.001) compared with patients in the lower UACR group (<10.2?mg/g). When UACR was analyzed as a continuous variable, every double of increased UACR, the OR for LVH was 1.511 (95% CI: 1.047-2.180, =0.028). Overall, UACR below 30?mg/g is associated with LVH in patients with T2DM. The optimal cutoff value of UACR for identifying LVH in diabetes is 10?mg/g.
  
  Copyright © 2020 Xiangkun Xie et al.
  
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• HuR (Human Antigen R) Regulates the Contraction of Vascular Smooth Muscle and Maintains Blood Pressure.
  Arterioscler Thromb Vasc Biol

  2020 Feb;():ATVBAHA119313897. doi: 10.1161/ATVBAHA.119.313897.
  
  Liu Shanshan, Jiang Xiuxin, Lu Hanlin, Xing Mengdan, Qiao Yanning, Zhang Cheng, Zhang Wencheng,
  
  Abstract
  
  OBJECTIVE:
  HuR (human antigen R)-an RNA-binding protein-is involved in regulating mRNA stability by binding adenylate-uridylate-rich elements. This study explores the role of HuR in the regulation of smooth muscle contraction and blood pressure. Approach and Results: Vascular HuR (smooth muscle-specific HuR knockout) mice were generated by crossbreeding HuR mice with ?-SMA (?-smooth muscle actin)-Cre mice. As compared with CTR (control) mice, HuR mice showed hypertension and cardiac hypertrophy. HuR levels were decreased in aortas from hypertensive patients and SHRs (spontaneously hypertensive rats), and overexpression of HuR could lower the blood pressure of SHRs. Contractile response to vasoconstrictors was increased in mesenteric artery segments isolated from HuR mice. The functional abnormalities in HuR mice were attributed to decreased mRNA and protein levels of RGS (regulator of G-protein signaling) protein(s) RGS2, RGS4, and RGS5, which resulted in increased intracellular calcium increase. Consistently, the degree of intracellular calcium ion increase in HuR-deficient smooth muscle cells was reduced by overexpression of RGS2, RGS4, or RGS5. Finally, administration of RGS2 and RGS5 reversed the elevated blood pressure in HuR mice.
  
  CONCLUSIONS:
  Our findings indicate that HuR regulates vascular smooth muscle contraction and maintains blood pressure by modulating RGS expression.
  
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• P-TEFb as A Promising Therapeutic Target.
  Molecules

  2020 Feb;25(4):. doi: E838.
  
  Fujinaga Koh,
  
  Abstract
  
  The positive transcription elongation factor b (P-TEFb) was first identified as a general factor that stimulates transcription elongation by RNA polymerase II (RNAPII), but soon afterwards it turned out to be an essential cellular co-factor of human immunodeficiency virus (HIV) transcription mediated by viral Tat proteins. Studies on the mechanisms of Tat-dependent HIV transcription have led to radical advances in our knowledge regarding the mechanism of eukaryotic transcription, including the discoveries that P-TEFb-mediated elongation control of cellular transcription is a main regulatory step of gene expression in eukaryotes, and deregulation of P-TEFb activity plays critical roles in many human diseases and conditions in addition to HIV/AIDS. P-TEFb is now recognized as an attractive and promising therapeutic target for inflammation/autoimmune diseases, cardiac hypertrophy, cancer, infectious diseases, etc. In this review article, I will summarize our knowledge about basic P-TEFb functions, the regulatory mechanism of P-TEFb-dependent transcription, P-TEFb's involvement in biological processes and diseases, and current approaches to manipulating P-TEFb functions for the treatment of these diseases.
  
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• Multiple Roles of sFRP2 in Cardiac Development and Cardiovascular Disease.
  Int J Biol Sci

  2020 ;16(5):730-738. doi: 10.7150/ijbs.40923.
  
  Wu Yu, Liu Xinyue, Zheng Haoxiao, Zhu Hailan, Mai Weiyi, Huang Xiaohui, Huang Yuli,
  
  Abstract
  
  The Wnt signaling pathway plays important roles in organ development and disease processes. Secreted frizzled-related protein 2 (sFRP2), a vital molecule of Wnt signaling, can regulate cardiac development and cardiovascular disease. Recent studies have suggested that sFRP2 is not only an antagonist of the canonical Wnt signaling pathway, but also has a more complex relationship in myocardial fibrosis, angiogenesis, cardiac hypertrophy and cardiac regeneration. Here, we review the role of sFRP2 and Wnt signaling in cardiac development and cardiovascular disease.
  
  © The author(s).
  
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• Fibroblast growth factor-inducible 14 mediates macrophage infiltration in heart to promote pressure overload-induced cardiac dysfunction.
  Life Sci

  2020 Feb;():117440. doi: S0024-3205(20)30188-0.
  
  Unudurthi Sathya D, Nassal Drew M, Patel Nehal J, Thomas Evelyn, Yu Jane, Pierson Curtis G, Bansal Shyam S, Mohler Peter J, Hund Thomas J,
  
  Abstract
  
  AIMS:
  Heart failure (HF) is characterized by compromised cardiac structure and function. Previous work has identified a link between upregulation of pro-inflammatory cytokines and HF. Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a pro-inflammatory cytokine, which binds to fibroblast growth factor inducible 14 (Fn14), a ubiquitously expressed cell-surface receptor. The objective of this study was to investigate the role of TWEAK/Fn14 pathway in promoting cardiac inflammation under non ischemic stress conditions.
  
  MAIN METHODS:
  Wild type (WT) and Fn14 knock out (Fn14) mice were subjected to pressure overload [transaortic constriction (TAC)] for 1 or 6?weeks. A subset of WT TAC animals were treated with the Fn14 antagonist L524-0366. Cardiac function was measured by echocardiography. Cardiac fibrosis and macrophage infiltration were quantified using immunohistochemistry and flow cytometry, respectively. Cardiac fibroblasts were isolated for quantifying TWEAK-induced chemokine release.
  
  KEY FINDINGS:
  Fn14 mice displayed improved cardiac function, reduced fibrosis and lower macrophage infiltration in heart compared to WT following TAC. L524-0366 mitigated maladaptive remodeling with TAC. TWEAK induced secretion of the pro-inflammatory chemokine, monocyte chemoattractant protein 1 from WT but not Fn14 fibroblasts in vitro, in part through activation of non-canonical NF-?B signaling. Finally, Fn14 expression was increased in mouse following TAC and in human failing hearts.
  
  SIGNIFICANCE:
  Our findings support an important role for the TWEAK/Fn14 promoting macrophage infiltration and fibrosis in heart under non-ischemic stress, with potential for therapeutic intervention to improve cardiac function in the setting of HF.
  
  Copyright © 2020. Published by Elsevier Inc.
  
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