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Pubblicazioni recenti - cardiac hypertrophy
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Anti-hypertrophic effect of Na/H exchanger-1 inhibition is mediated by reduced cathepsin B.
Eur J Pharmacol2020 Aug;():173420. doi: S0014-2999(20)30512-4.
Riaz Sadaf, Abdulrahman Nabeel, Uddin Shahab, Jabeen Ayesha, Gadeau Alain P, Fliegel Larry, Mraiche Fatima,
Abstract
Previous studies have established the role of Na/H exchanger isoform-1 (NHE1) and cathepsin B (Cat B) in the development of cardiomyocyte hypertrophy (CH). Both NHE1 and Cat B are activated under acidic conditions suggesting that their activities might be interrelated. The inhibition of NHE1 has been demonstrated to reduce cardiac hypertrophy but the mechanism that contributes to the anti-hypertrophic effect of NHE1 inhibition still remains unclear. H9c2 cardiomyoblasts were stimulated with Angiotensin (Ang) II in the presence and absence of N-[2-methyl-4,5-bis(methylsulphonyl)-benzoyl]-guanidine, hydrochloride (EMD, EMD 87580), an NHE1 inhibitor or CA-074Me, a Cat B inhibitor, and various cardiac hypertrophic parameters, namely cell surface area, protein content and atrial natriuretic peptide (ANP) mRNA were analyzed. EMD significantly suppressed markers of cardiomyocyte hypertrophy and inhibited Ang II stimulated Cat B protein and gene expression. Cat B is located within the acidic environment of lysosomes. Cat B proteases are released into the cytoplasm upon disintegration of the lysosomes. EMD or CA-074Me prevented the dispersal of the lysosomes induced by Ang II and reduced the ratio of LC3-II to LC3-I, a marker of autophagy. Moreover, Cat B protein expression and MMP-9 activity in the extracellular space were significantly attenuated in the presence of EMD or CA-074Me. Our study demonstrates a novel mechanism for attenuation of the hypertrophic phenotype by NHE1 inhibition that is mediated by a regression in Cat B. The inhibition of Cat B via EMD or CA-074Me attenuates the autosomal-lysosomal pathway and MMP-9 activation.
Copyright © 2020. Published by Elsevier B.V.
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Potential effect of new (E)-4-hydroxy -N'-(1-(7-hydroxy-2-oxo-2H-chromen-3-yl) ethylidene) benzohydrazide against acute myocardial infarction: Hemodynamic, biochemical and histological studies.
Clin Exp Pharmacol Physiol2020 Aug;():. doi: 10.1111/1440-1681.13397.
Mnafgui Kais, Khdhiri Emna, Hajji Raouf, Feriani Anouar, da Silva Francisco Ivan, da Silva Santos Antônia Laíres, Tlili Abir, Mlayeh Souhail, Bouzidi Moncef, Ammar Houcine, Abid Souhir,
Abstract
This study aimed to explore the cardioprotective effect of new synthesized coumarin (E)-4-hydroxy-N'-(1-(7-hydroxy-2-oxo-2H-chromen-3-yl) ethylidene) benzohydrazide denoted (Hyd.Cou) against myocardial infarction disorders. Male Wistar rats were divided into four groups; Control, ISO, ISO+ Ac (Acenocoumarol) and ISO+ Hyd.Cou. Results showed that ISO group exhibited serious alteration in EGC pattern, significant heart hypertrophy (+33%), hemodynamic disturbance and increase in plasma rate of CK-MB, LDH and troponin-T by 44, 53, and 170%, respectively, as compared to Control. Moreover, isoproterenol induced a rise in plasma angiotensin-converting enzyme activity (ACE) by 49%, dyslipidemia, and increased Thiobarbituric acid-reactive substances (TBARS) by 117% associated with decrease in the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) by 46% and 58%, respectively in myocardium. Interestingly, the molecular docking calculation demonstrated strong interactions of Hyd.Cou with the receptors of the protein disulfide isomerase (PDI) which could highlight the antithrombotic effect. Moreover, Hyd.Cou improved plasma cardiac dysfunction biomarkers, mitigated the ventricle remodeling process and alleviated heart oxidative stress damage. Overall, Hyd.Cou prevented the heart from remodeling process through inhibition of ACE activity and oxidative stress improvement.
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Loss of APJ mediated ?-arrestin signalling improves high-fat diet induced metabolic dysfunction but does not alter cardiac function in mice.
Biochem J2020 Aug;():. doi: BCJ20200343.
Li Na, Ma Xiaochuan, Ban Ting, Xu Shaohua, Ma Yingli, Ason Brandon, Hu Liaoyuan A,
Abstract
Apelin receptor (APJ) is a G protein-coupled receptor that contributes to many physiological processes and is emerging as a therapeutic target to treat a variety of diseases. For most disease indications the role of G protein vs ?-arrestin signalling in mitigating disease pathophysiology remains poorly understood. This hinders the development of G protein biased APJ agonists, which have been proposed to have several advantages over balanced APJ signalling agonists. To elucidate the contribution of APJ ?-arrestin signalling, we generated a transgenic mouse harbouring a point mutation (APJ I107A) that maintains full G protein activity but fails to recruit ?-arrestin following receptor activation. APJ I107A mutant mice did not alter cardiac function at rest, following exercise challenge or in response to pressure overload induced cardiac hypertrophy. Additionally, APJ I107A mice have comparable body weights, plasma glucose and lipid levels to WT mice when fed a chow diet. However, APJ I107A mice showed significantly lower body weight, blood insulin levels, improved glucose tolerance and greater insulin sensitivity when fed a high fat diet. Furthermore, loss of APJ ?-arrestin signalling also affected fat composition and the expression of lipid metabolism related genes in adipose tissue from high-fat fed mice. Taken together, our results suggest that G protein biased APJ activation may be more effective for certain disease indications given that loss of APJ mediated ?-arrestin signalling appears to mitigate several aspects of diet induced metabolic dysfunction.
Copyright 2020 The Author(s).
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Impact of Long-Term Burden of Body Mass Index and Blood Pressure From Childhood on Adult Left Ventricular Structure and Function.
J Am Heart Assoc2020 Aug;():na. doi: 10.1161/JAHA.120.016405.
Liu Yang, Yan Yinkun, Jiang Tingbo, Li Shengxu, Guo Yajun, Fernandez Camilo, Barshop Rupert, Bazzano Lydia, He Jiang, Chen Wei,
Abstract
Background Data are limited regarding the relationship between the life-course burden of risk factors and adult cardiac function. This study sought to examine the impact of long-term burden of body mass index (BMI) and blood pressure (BP) levels on changes in adult left ventricular (LV) structure and function in a community-based cohort. Methods and Results The longitudinal study cohort consisted of 1108 adult patients (726 White; 41.9% men; mean age, 48.2 years in the last survey) who had been examined 4 to 16 times for BMI and BP and echocardiographic LV structure and function in adulthood, with a mean follow-up period of 38.8 years. The area under the curve was used as a measure of long-term burden of BMI and BP. Adult LV mass index was significantly associated with childhood and adulthood BMI and systolic BP (SBP), and their area under the curve values (?=0.07-0.37; <0.05 for all). Adult LV ejection fraction was negatively associated with childhood BMI (?=-0.08), adult BMI (?=-0.07) and BMI area under the curve (?=-0.07) (<0.05 for all); the effects of SBP measures were not significant. Adult E/A ratio was negatively associated with adulthood SBP (?=-0.13; <0.01) and total area under the curve of SBP (?=-0.13; <0.01). E/e' ratio was positively associated with BMI and SBP measures. The effects of diastolic BP measures were substantially similar to those of SBP measures. Participants with LV hypertrophy, eccentric hypertrophy, and concentric hypertrophy had significantly lower LV ejection fraction and higher E/e' ratio. Conclusions These observations provide strong evidence that early-life adiposity and BP levels and their life-course cumulative burdens are associated with subclinical changes in adult LV structure and function in the general population.
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The Changes of Heart miR-1 and miR-133 Expressions following Physiological Hypertrophy Due to Endurance Training.
Cell J2020 Jul;22(Suppl 1):133-140. doi: 10.22074/cellj.2020.7014.
Fathi Mohammad, Gharakhanlou Reza, Rezaei Razieh,
Abstract
Objective:
MicroRNAs (miRNAs) play a key role in the development of the heart. Recent studies have shown that miR- 1 and miR-133 are key regulators of cardiac hypertrophy. Therefore, we aimed to evaluate the effect of an endurance training (ET) program on the expressions of these miRNAs and their transcriptional network.
Materials and Methods:
In this experimental study, cardiac hypertrophy was induced by 14 weeks of ET for 1 hour per day, 6 days per week at 75% VO2 max). The rats (221 ± 23 g) in the experimental (n=7) and control (n=7) groups were anesthetized to evaluate heart morphology changes by echocardiography. Next, we evaluated expressions of miR-1 and miR-133, and heart and neural crest derivatives express 2 , , histone deacetylase 4 (Hdac4) and serum response factor () gene expressions by real-time polymerase chain reaction (PCR). Finally, the collected data were evaluated by the independent t test to determine differences between the groups.
Results:
The echocardiography result confirmed physiological hypertrophy in the experimental group that underwent ET as shown by the increased left ventricular weight/body surface area (LVW/BSA) (P=0.004), LVW/body weight (BW) (P=0.011), left ventricular diameter end-diastolic (LVDd) (P=0.003), and improvements in heart functional indexes such as fractional shortness (FS) (P=0.036) and stroke volume (SV) (P=0.002). There were significant increases in the expressions of miR-1 (P=0.001) and miR-133 (P=0.004). The expressions of , and genes significantly increased (P<0.001) in the experimental group Compared with the control group. The expression of did not significantly change.
Conclusion:
The expressions of miR-1 and miR-133 and their target genes appeared to be involved in physiological hypertrophy induced by ET in these rats.
Copyright© by Royan Institute. All rights reserved.
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Alleviation of salt-induced exacerbation of cardiac, renal, and visceral fat pathology in rats with metabolic syndrome by surgical removal of subcutaneous fat.
Nutr Diabetes2020 08;10(1):28. doi: 10.1038/s41387-020-00132-1.
Aoyama Kiyoshi, Komatsu Yuki, Yoneda Mamoru, Nakano Shiho, Ashikawa Sao, Kawai Yumeno, Cui Xixi, Ikeda Katsuhide, Nagata Kohzo,
Abstract
OBJECTIVES:
Evidence suggests that visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) should be considered as distinct types of white fat. Although VAT plays a key role in metabolic syndrome (MetS), the role of subcutaneous adipose tissue (SAT) has been unclear. DahlS.Z-Lepr/Lepr (DS/obese) rats, an animal model of MetS, develop adipocyte hypertrophy and inflammation to similar extents in SAT and VAT. We have now investigated the effects of salt loading and SAT removal on cardiac, renal, and VAT pathology in DS/obese rats.
METHODS:
DS/obese rats were subjected to surgical removal of inguinal SAT or sham surgery at 8 weeks of age. They were provided with a 0.3% NaCl solution as drinking water or water alone for 4 weeks from 9 weeks of age.
RESULTS:
Salt loading exacerbated hypertension, insulin resistance, as well as left ventricular (LV) hypertrophy, inflammation, fibrosis, and diastolic dysfunction in DS/obese rats. It also reduced both SAT and VAT mass but aggravated inflammation only in VAT. Although SAT removal did not affect LV hypertrophy in salt-loaded DS/obese rats, it attenuated hypertension, insulin resistance, and LV injury as well as restored fat mass and alleviated inflammation and the downregulation of adiponectin gene expression in VAT. In addition, whereas salt loading worsened renal injury as well as upregulated the expression of renin-angiotensin-aldosterone system-related genes in the kidney, these effects were suppressed by removal of SAT.
CONCLUSIONS:
SAT removal attenuated salt-induced exacerbation of MetS and LV and renal pathology in DS/obese rats. These beneficial effects of SAT removal are likely attributable, at least in part, to inhibition of both VAT and systemic inflammation.
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Changes in left atrial function, left ventricle remodeling, and fibrosis after septal myectomy for obstructive hypertrophic cardiomyopathy.
J Thorac Cardiovasc Surg2020 Jul;():. doi: S0022-5223(20)31551-8.
Tang Bing, Song Yunhu, Yang Qiulan, Cui Hao, Ji Keshan, Zhao Shihua, Wang Shuiyun,
Abstract
BACKGROUND:
This study aimed to investigate the impact of septal myectomy on left atrial function, left ventricle remodeling, and fibrosis in patients with obstructive hypertrophic cardiomyopathy.
METHOD:
From May 2012 to September 2016, preoperative cardiac magnetic resonance imaging of 507 adult patients who underwent septal myectomy at Fuwai Hospital was retrospectively collected. Until October 2019, 57 patients were followed up with postoperative cardiac magnetic resonance imaging at 11.9 months (interquartile range, 6.4-25.3). Preoperative and postoperative left atrium and left ventricle changes, as well as late gadolinium enhancement as a surrogate of myocardial fibrosis, were analyzed.
RESULTS:
Patients with hypertrophic cardiomyopathy requiring myectomy showed increased left atrium volume, stroke volume, left ventricular ejection fraction, and left ventricle mass, as well as decreased left ventricle end-systolic volume. Echocardiography demonstrated that myectomy decreased the left ventricle outflow tract gradient, left atrium diameter, left ventricular ejection fraction, and posterior wall thickness. Postoperative cardiac magnetic resonance imaging showed that the minimal left atrium volume (P < .001), stroke volume (P = .009), left ventricle ejection fraction (P < .001), and left ventricle mass (166.9 [interquartile range, 135.8] vs 149.3 [interquartile range, 100.5] g, P < .001) decreased, whereas the left ventricle end-systolic volume (P = .001) and left atrium ejection fraction (37.9% ± 14.6% vs 47.8% ± 14%, P < .001) increased. However, left ventricle myocardial fibrosis, as detected by late gadolinium enhancement, still progressed after myectomy in patients with obstructive hypertrophic cardiomyopathy (15.2% ± 9.6% vs 18.6% [interquartile range, 21.6], P = .009).
CONCLUSIONS:
Septal myectomy alleviated left ventricle hypertrophy and reversed left atrium and left ventricle remodeling in patients with obstructive hypertrophic cardiomyopathy. Late gadolinium enhancement in the left ventricle increased despite myectomy in patients with obstructive hypertrophic cardiomyopathy.
Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
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The endocrinological component and signaling pathways associated to cardiac hypertrophy.
Mol Cell Endocrinol2020 Aug;():110972. doi: S0303-7207(20)30272-0.
Takano Ana Paula Cremasco, Senger Nathalia, Barreto-Chaves Maria Luiza M,
Abstract
Although myocardial growth corresponds to an adaptive response to maintain cardiac contractile function, the cardiac hypertrophy is a condition that occurs in many cardiovascular diseases and typically precedes the onset of heart failure. Different endocrine factors such as thyroid hormones, insulin, insulin-like growth factor 1 (IGF-1), angiotensin II (Ang II), endothelin (ET-1), catecholamines, estrogen, among others represent important stimuli to cardiomyocyte hypertrophy. Thus, numerous endocrine disorders manifested as changes in the local environment or multiple organ systems are especially important in the context of progression from cardiac hypertrophy to heart failure. Based on that information, this review summarizes experimental findings regarding the influence of such hormones upon signalling pathways associated with cardiac hypertrophy. Understanding mechanisms through which hormones differentially regulate cardiac hypertrophy could open ways to obtain therapeutic approaches that contribute to prevent or delay the onset of heart failure related to endocrine diseases.
Copyright © 2020. Published by Elsevier B.V.
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Tale of fat and fib - cardiac lipoma managed with radiofrequency ablation: A case report.
World J Cardiol2020 Jun;12(6):285-290. doi: 10.4330/wjc.v12.i6.285.
Nalluru Swarna Sri, Nadadur Srinivas, Trivedi Nitin, Trivedi Sunita, Goyal Sanjeev,
Abstract
BACKGROUND:
Cardiac lipoma and lipomatous hypertrophy of interatrial septum (LHIS) are very rare disorders with distinct pathological features. While cardiac lipoma is a well-circumscribed encapsulated tumor of mature adipocytes, LHIS is due to entrapment of fat cells in the interatrial septum during embryogenesis. Although a biopsy is the definitive diagnostic test, these disorders can be differentiated by a cardiac magnetic resonance imaging (MRI). Treatment of LHIS is not warranted in asymptomatic patients. In symptomatic patients, surgical resection is the only recommended treatment, which has shown to improve good long-term prognosis.
CASE SUMMARY:
A 63-year-old Caucasian woman with past medical history significant for hypertension, hypothyroidism, right breast ductal cell carcinoma treated with mastectomy and breast implant, platelet granule disorder, asthma requiring chronic intermittent prednisone use, presented to the outpatient cardiology office with recent onset exertional dyspnea, palpitations, weight gain and weakness. Initial workup with electrocardiogram and holter monitor did not reveal significant findings. During the subsequent hospitalization for community acquired pneumonia, the patient developed symptomatic paroxysmal atrial fibrillation. Transthoracic echocardiogram showed a right ventricular mass. A biopsy was not pursued given the high risk of bleeding due to platelet granule disorder. Cardiac MRI showed characteristic features consistent with cardiac lipoma and LHIS. Prednisone was discontinued. Genetic testing for arrhythmogenic right ventricular dysplasia and 24-h urine cortisol test was negative. As multiple attempts at rhythm control failed with sotalol and flecainide, pulmonary vein isolation and right atrial isthmus radiofrequency ablation were done. She is in follow-up with symptomatic relief and no recurrence of atrial fibrillation for 10 mo.
CONCLUSION:
Benign fatty lesions in heart include solitary lipoma, lipomatous infiltration and lipomatous hypertrophy of interatrial septum. Although transvenous biopsy provides a definitive diagnosis, Cardiac MRI is superior to computed tomography and aids in differentiating benign from malignant lesions. Surgical excision of cardiac lipoma along with capsule and pedicle removal generally prevents recurrence, but with our patient's unusual tumor features and comorbidities proscribed a surgical approach. Symptom management with antiarrhythmics and ablation techniques were successfully utilized.
©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
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Long Noncoding RNA Rps4l Mediates the Proliferation of Hypoxic Pulmonary Artery Smooth Muscle Cells.
Hypertension2020 Aug;():HYPERTENSIONAHA12014644. doi: 10.1161/HYPERTENSIONAHA.120.14644.
Liu Ying, Zhang Hongyue, Li Yiying, Yan Lixin, Du Wei, Wang Siqi, Zheng Xiaodong, Zhang Min, Zhang Junting, Qi Jing, Sun Hanliang, Zhang Lixin, Li Guangqun, Zhu Daling,
Abstract
Pulmonary hypertension (PH) is a rare and fatal disorder involving the vascular remodeling of pulmonary arteries mediated by the enhanced proliferation of pulmonary artery smooth muscle cells (PASMCs). Long noncoding RNAs are a subclass of regulatory molecules with diverse cellular functions, but their role in PH remains largely unexplored. We aimed to identify and determine the functions of long noncoding RNAs involved in hypoxia-induced PH and PASMC proliferation. RNA sequencing in a hypoxic mouse model identified hypoxia-regulated long noncoding RNAs, including Rps4l. Rps4l expression was significantly reduced in PH-model mice and hypoxic PASMCs. The subcellular localization of Rps4l was detected by RNA fluorescence in situ hybridization and quantification of nuclear/cytoplasmic RNA. Rps4l overexpression rescued pulmonary arterial hypertension features, as demonstrated by right ventricle hypertrophy, right ventricular systolic pressure, hemodynamics, cardiac function, and vascular remodeling. At the cellular level, Rps4l overexpression weakened cell viability and proliferation and suppressed cell cycle progression. Potential Rps4l-binding proteins were identified via RNA pull-down followed by mass spectrometry, RNA immunoprecipitation, and microscale thermophoresis. These results indicated that Rps4l is associated with and affects the stabilization of ILF3 (interleukin enhancer-binding factor 3). Rps41 further regulates the levels of HIF-1? and consequently leads to hypoxia-induced PASMC proliferation and migration. Our results showed that in hypoxic PASMCs, Rps4l expression decreases due to regulation by hypoxia. This decrease affects the proliferation, migration, and cell cycle progression of PASMCs through ILF3/HIF-1?. These results provide a theoretical basis for further investigations into the pathological mechanism of hypoxic PH and may provide insight for the development of novel treatments.
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Left Ventricular Mass Index Is Associated With Cognitive Function in Middle-Age: Bogalusa Heart Study.
Circ Cardiovasc Imaging2020 08;13(8):e010335. doi: 10.1161/CIRCIMAGING.119.010335.
Razavi Alexander C, Fernandez Camilo, He Jiang, Kelly Tanika N, Krousel-Wood Marie, Whelton Seamus P, Carmichael Owen T, Bazzano Lydia A,
Abstract
BACKGROUND:
Elevated cardiovascular disease risk factor burden is a recognized contributor to poorer cognitive function; however, the physiological mechanisms underlying this association are not well understood. We sought to assess the potential mediation effect of left ventricular (LV) remodeling on the association between lifetime systolic blood pressure and cognitive function in a community-based cohort of middle-aged adults.
METHODS:
Nine hundred sixty participants of the Bogalusa Heart Study (59.2% women, 33.8% black, aged 48.4±5.1 years) received 2-dimensional echocardiography to quantify relative wall thickness, LV mass, and diastolic and systolic LV function; and a standardized neurocognitive battery to assess memory, executive functioning, and language processing. Multivariable linear regression assessed the association of cardiac structure and function with a global composite cognitive function score, adjusting for traditional cardiovascular disease risk factors. Mediation analysis assessed the effect of LV mass index on the association between lifetime systolic blood pressure burden and cognitive function.
RESULTS:
There were 233 (24.3%) and 136 (14.2%) individuals with concentric LV remodeling and concentric LV hypertrophy, respectively. Each g/m increment in LV mass index was associated with a 0.03 standardized unit decrement in global cognitive function (=0.03). Individuals with concentric LV remodeling and isolated diastolic dysfunction had the poorest cognitive function, and a greater ratio between early mitral inflow velocity and early diastolic mitral annular velocity (E/e') was associated with poorer cognitive function, even after adjustment for LV mass index (B=-0.12; =0.03). A total of 18.8% of the association between lifetime systolic blood pressure burden and midlife cognitive function was accounted for by LV mass index.
CONCLUSIONS:
Cardiac remodeling partially mediates the association between lifespan systolic blood pressure burden and adult cognition in individuals without dementia or clinical cardiovascular disease. Slowing or reversing the progression of cardiac remodeling in middle-age may be a novel therapeutic approach to prevent cognitive decline.
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Cardiac arrhythmias in arterial hypertension.
J Clin Hypertens (Greenwich)2020 Aug;():. doi: 10.1111/jch.13989.
Varvarousis Dimitrios, Kallistratos Manolis, Poulimenos Leonidas, Triantafyllis Andreas, Tsinivizov Pavlos, Giannakopoulos Andreas, Kyfnidis Konstantinos, Manolis Athanasios,
Abstract
Patients with arterial hypertension frequently manifest various cardiac rhythm disturbances, ranging from bradyarrhythmias to supraventricular premature beats, atrial fibrillation, or other supraventricular and ventricular tachyarrhythmias. These cardiac arrhythmias may either cause symptoms or be completely asymptomatic, depending on the underlying cardiac function. Degenerative electrical disease and left ventricular hypertrophy constitute the principal pathophysiological mechanisms. This review summarizes all important existing evidence on cardiac arrhythmia manifestation in the setting of arterial hypertension, and it highlights known underlying pathophysiological mechanisms and therapeutic considerations.
© 2020 Wiley Periodicals LLC.
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Erratum to "Epigallocathechin-3 gallate inhibits cardiac hypertrophy through blocking reactive oxidative species-dependent and -independent signal pathways" [Free Radical Biol. Med. 40 (2006) 1756-1775].
Free Radic Biol Med2020 Aug;():. doi: S0891-5849(20)31151-5.
Li Hong-Liang, Huang Yue, Zhang Chan-Na, Liu Guang, Wei Yu-Sheng, Wang Ai-Bing, Liu Yu-Qing, Hui Rui-Tai, Wei Chiming, Williams G Metville, Liu De-Pei, Liang Chih-Chuan,
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Three Cases of Karoshi Without the Typical Pathomorphological Features of Cardiovascular/Cerebrovascular Disease.
Am J Forensic Med Pathol2020 Aug;():. doi: 10.1097/PAF.0000000000000600.
Miao Qi, Li Jing, Pan Yu-Peng, Yu Yan-Geng, Zhang Fu, Xiao Ning, Li Dong-Ri,
Abstract
Karoshi is a term used to describe unexplained sudden death associated with overwork and has become a serious public health issue in China. Cases have occurred in physicians, university professors, engineers in high-tech companies, and blue-collar workers. The mechanisms associated with death by overwork are very complex. According to most researchers, karoshi is considered to be caused by an excessive workload that induces deterioration of underlying hypertension or atherosclerosis. These conditions inevitably lead to death from cardiovascular or cerebrovascular diseases. However, in our own experience, we have found that in some cases, the victims of karoshi were in a chronic state of overwork but without a history of cardiovascular or cerebrovascular diseases. In support of this, we have found that even autopsies have revealed few positive findings except for cardiac hypertrophy. In this article, we report 3 typical cases of karoshi but without the typical pathomorphological features of cardiovascular or cerebrovascular disease.
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Risk factors for fatal drowning in a Greek region: a retrospective case-control study.
Inj Prev2020 Aug;():. doi: injuryprev-2020-043788.
Kevrekidis Dimitrios Phaedon, Brousa Evdokia, Mastrogianni Orthodoxia, Orfanidis Amvrosios, Gika Helen G, Raikos Nikolaos,
Abstract
BACKGROUND:
Fatal drowning is one of the leading causes of unintentional injury mortality worldwide and a persistent public health concern in Greece. While several pathologic and sociodemographic contributing factors have been previously identified, these have not been extensively investigated in conjunction with the effects of psychoactive substances.
METHODS:
A retrospective case-control study of drowning deaths was conducted in the Greek regions of Northern Greece and Thessaly during a 10-year period. A regression model was constructed examining differences in detected substances, autopsy findings and sociodemographic characteristics between 240 victims of unintentional fatal submersion and 480 victims of other causes of sudden or violent death.
RESULTS:
The majority of victims were males (69.4%) and foreign nationality was associated with increased odds of drowning. Cardiomegaly and coronary bypass grafts were significantly more likely to have been recorded among drowning victims, while the frequency of other circulatory system disorders was also elevated. Several of these findings were potential arrhythmogenic substrates which could adversely interact with the diving reflex. Selective serotonin reuptake inhibitors (SSRIs) were the most commonly detected pharmacological group (9.0%), and along with tramadol, there was an increased likelihood of exposure to them. These drugs have been previously associated with QT prolongation and other adverse effects which may contribute to fatal outcomes in a seawater environment. In contrast, there was a decreased risk of exposure to dependence-inducing drugs and paracetamol.
CONCLUSIONS:
Male sex, older age, foreign nationality and cardiovascular disease predisposed individuals to an elevated risk of fatal submersion. SSRI antidepressants and tramadol may contribute to this outcome.
© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.
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?-adrenergic activation may promote myosin light chain kinase degradation through calpain in pressure overload-induced cardiac hypertrophy: ?-adrenergic activation results in MLCK degradation.
Biomed Pharmacother2020 Jul;129():110438. doi: S0753-3322(20)30631-4.
Wang Shun, Wang Haixiong, Su Xiaoling, Liu Beilei, Wang Le, Yan Hui, Mao Shuai, Huang He, Huang Congxin, Cheng Mian, Wu Gang,
Abstract
BACKGROUND:
?-adrenergic activation is able to exacerbate cardiac hypertrophy. Myosin light chain kinase (MLCK) and its phosphorylated substrate, phospho-myosin light chain 2 (p-MLC2), play vital roles in regulating cardiac hypertrophy. However, it is not yet clear whether there is a relationship between ?-adrenergic activation and MLCK in the progression of cardiac hypertrophy. Therefore, we explored this relationship and the underlying mechanisms in this work.
METHODS:
Cardiac hypertrophy and cardiomyocyte hypertrophy were induced by pressure overload and isoproterenol (ISO) stimulation, respectively. Echocardiography, histological analysis, immunofluorescence and qRT-PCR were used to confirm the successful establishment of the models. A ?-blocker (metoprolol) and a calpain inhibitor (calpeptin) were administered to inhibit ?-adrenergic activity in rats and calpain in cardiomyocytes, respectively. The protein expression levels of MLCK, myosin light chain 2 (MLC2), p-MLC2, myosin phosphatase 2 (MYPT2), calmodulin (CaM) and calpain were measured using western blotting. A cleavage assay was performed to assess the degradation of recombinant human MLCK by recombinant human calpain.
RESULTS:
The ?-blocker alleviated cardiac hypertrophy and dysfunction, increased MLCK and MLC2 phosphorylation and decreased calpain expression in pressure overload-induced cardiac hypertrophy. Additionally, the calpain inhibitor calpeptin attenuated cardiomyocyte hypertrophy, upregulated MLCK and p-MLC2 and reduced MLCK degradation in ISO-induced cardiomyocyte hypertrophy. Recombinant human calpain degraded recombinant human MLCK in vitro in concentration- and time-dependent manners, and this degradation was inhibited by the calpain inhibitor calpeptin.
CONCLUSION:
Our study suggested that ?-adrenergic activation may promote the degradation of MLCK through calpain in pressure overload-induced cardiac hypertrophy.
Copyright © 2020. Published by Elsevier Masson SAS.
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Acupuncture Reduces Hypertrophy and Cardiac Fibrosis, and Improves Heart Function in Mice with Diabetic Cardiomyopathy.
Cardiovasc Drugs Ther2020 Aug;():. doi: 10.1007/s10557-020-07043-4.
Ye Yumei, Birnbaum Yochai, Widen Steven G, Zhang Zhaohui, Zhu Shipeng, Bajaj Mandeep, Chen Huan,
Abstract
PURPOSE:
To assess the effects of electro-acupuncture (EA) on glycemic control, myocardial inflammation, and the progression of diabetic cardiomyopathy in mice with type 2 diabetes.
METHODS:
Db/Db mice received EA at PC6+ST36 (DM-Acu), non-acupoint simulation (DM-Sham), or no treatment (DM). EA was applied for 30 min per day, 5 days a week for 4 weeks. Heart function was assessed by echocardiography. Myocardium was assessed by RT-PCR, immunoblotting, and histology. Serum TNF-?, IL-1?, IL-1?, IL-6, and IL-8 were measured.
RESULTS:
DM-Acu, but not DM-Sham, reduced fasting blood glucose without affecting body weight. DM decreased systolic function. DM-Acu, but not DM-Sham, attenuated the decrease in systolic function. Heart weight was significantly smaller in the DM-Acu than in the DM and DM-Sham groups. Percent fibrosis and apoptosis were reduced in the DM-Acu, but not the DM-Sham, group. Serum levels of IL-1?, IL-1?, IL-6, IL-8, ICAM-1, MCP-1, and TNF-? were significantly lower in the DM-Acu than in the DM or DM-Sham groups. Protein levels of P-Akt and P-AMPK and mRNA levels of phosphoinositide-3-kinase regulatory subunit 6 (PIK3r6) were significantly higher in the DM-Acu group. Myocardial mRNA and protein levels of insulin-like growth factor 1 receptor (IGF1R) were significantly lower in the DM and DM-Sham groups compared with the DM-Acu group.
CONCLUSIONS:
EA reduced serum glucose; prevented DM-induced hypertrophy and deterioration of systolic function, inflammation, and fibrosis; and restored IGF1R, P-Akt, and P-AMPK levels in mice with type 2 diabetes mellitus.
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Subclinical Left Ventricular Dysfunction in Severe Obesity and Reverse Cardiac Remodeling after Bariatric Surgery.
J Cardiovasc Echogr;30(1):22-28. doi: 10.4103/jcecho.jcecho_50_19.
Frea Simone, Andreis Alessandro, Scarlatta Vittoria, Rovera Chiara, Vairo Alessandro, Pistone Erika, Anselmino Matteo, Golzio Pier Giorgio, Toppino Mauro, Giustetto Carla, Gaita Fiorenzo,
Abstract
Aim:
Obesity is associated with an increased cardiovascular risk. This study aimed to assess the role of echocardiography in the early detection of subclinical cardiac abnormalities in a cohort of obese patients with a preserved ejection fraction (EF) undergoing bariatric surgery.
Methods and Results:
Forty consecutive severely obese patients (body mass index?35 kg/m2) referring to our center for bariatric surgery were enrolled in this prospective cohort study. Despite a baseline EF of 61% ± 3%, almost half patients (43%) had a systolic dysfunction (SD) defined as global longitudinal strain (GLS)>-18%, and most of them (60%) had left ventricular hypertrophy (LVH) or concentric remodeling (CR). At 10-months after surgery, body weight decreased from 120 ± 15 kg to 83 ± 12 kg, body mass index from 44 ± 5 kg/m to 31 ± 5 kg/m (both < 0.001). Septal and left ventricular posterior wall thickness decreased respectively from 10 ± 1 mm to 9 ± 1 mm ( = 0.004) and from 10 ± 1 mm to 9 ± 1 mm ( = 0.007). All systolic parameters improved: EF from 61% ± 3% to 64% ± 3% ( = 0.002) and GLS from -17% ± 2% to -20% ± 1% ( < 0.001). Epicardial fat thickness reduction (from 4.7 ± 1 mm to 3.5 ± 0.7 mm, < 0.001) correlated with the reduction of left atrial area ( < 0.001 R = 0.35) and volume ( = 0.02 R = 0.25). Following bariatric surgery, we observed a reduced prevalence of LVH/CR (before 60%, after 22%, = 0.001) and a complete resolution of preclinical SD (before 43%, after 0%, < 0.001). Moreover, a postoperative reduction of at least 30 kg correlated with regression of septal hypertrophy ( < 0.001).
Conclusions:
Obese patients candidate to bariatric surgery have an high prevalence of preclinical SD and LVH/CR, early detectable with echocardiography. Bariatric surgery is associated with reverse cardiac remodeling; it might also have a preventive effect on atrial fibrillation occurrence by reducing its substrate.
Copyright: © 2020 Journal of Cardiovascular Echography.
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Echocardiographic Changes in Chronic Kidney Disease Patients on Maintenance Hemodialysis.
Cureus2020 Jul;12(7):e8969. doi: 10.7759/cureus.8969.
Jameel Farah Anum, Junejo Abdul Mannan, Khan Qurat Ul Ain, Date Sudeep, Faraz Ahmad, Rizvi Syed Hasan Mustafa, Ahmad Fatima, Tahir Muhammad,
Abstract
Introduction Chronic kidney disease (CKD) carries a significant association with cardiac diseases, which suggests a minor reduction in the glomerular filtration rate (GFR) can act as an independent risk factor for causing cardiovascular abnormalities. Patients of CKD having cardiovascular disease (CVD) had three to thirty times higher risk of mortality as compared to the general population. In addition, mortality among cardiovascular patients has been found to be twofold higher in CKD stage 2 patients and three-fold higher in patients with stage 3 CKD, when collated to patients with normal renal function. Furthermore, cardiomyopathy among hemodialysis (HD) is due to the presence of coronary artery obstruction, reduction in coronary reserves, and left ventricular (LV) physiological-structural abnormalities secondary volume and pressure overload. Echocardiography is a gold standard diagnostic modality for the identification of cardiac structural and functional abnormalities. Therefore, the evaluation of echocardiographic parameters in patients of CKD can help to determine the risk and prognosis of CVD in patients of CKD. In the present study, we evaluated the echocardiographic findings in patients of CKD on maintenance hemodialysis. Methods This cross-sectional study was conducted in the nephrology unit of Jinnah Postgraduate Medical Center between March 2019 to October 2019. A total of 100 patients who were on maintenance for more than one year were included in the analysis. Two-dimensional transthoracic echocardiography was done in each patient for the determination of cardiac structural and functional parameters such as LV hypertrophy, LV systolic dysfunction, and LV diastolic dysfunction. Results The mean age of the patients was 46.9±12.8 years. There was male dominance with male/female ratio 63/37. There were 39% hypertensive and 62% anemic patients. LV dysfunction was diagnosed in 31% of patients, LV diastolic dysfunction in 47% patients, and left ventricular hypertrophy (LVH) in 55% of patients. LVH was found in 74.3% hypertensive patients versus only 42.6% non-hypertensive patients (p-value 0.001). LV systolic dysfunction was also high in hypertensive patients, 46.1% versus 21.3% patients in non-hypertensive patients (p-value 0.008). Conclusion There is a high frequency of cardiac functional and structural abnormalities in CKD patients on HD especially in patients having concomitant hypertension. LVH is the most common structural defect and LV diastolic dysfunction is the most common functional cardiac defect in CKD patients on hemodialysis.
Copyright © 2020, Jameel et al.
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p300 in Cardiac Development and Accelerated Cardiac Aging.
Aging Dis2020 Jul;11(4):916-926. doi: 10.14336/AD.2020.0401.
Ghosh Asish K,
Abstract
The heart is the first functional organ that develops during embryonic development. While a heartbeat indicates life, cessation of a heartbeat signals the end of life. Heart disease, due either to congenital defects or to acquired dysfunctions in adulthood, remains the leading cause of death worldwide. Epigenetics plays a key role in both embryonic heart development and heart disease in adults. Stress-induced vascular injury activates pathways involved in pathogenesis of accelerated cardiac aging that includes cellular dysfunction, pathological cardiac hypertrophy, diabetic cardiomyopathy, cardiac matrix remodeling, cardiac dysfunction and heart failure. Acetyltransferase p300 (p300), a major epigenetic regulator, plays a pivotal role in heart development during embryogenesis, as deficiency or abnormal expression of p300 leads to embryonic death at early gestation periods due to deformation of the heart and neural tube. Acetyltransferase p300 controls heart development through histone acetylation-mediated chromatin remodeling and transcriptional regulation of genes required for cardiac development. In adult hearts, p300 is differentially expressed in different chambers and epigenetically controls cardiac gene expression. Deregulation of p300, in response to prohypertrophic and profibrogenic stress signals, is associated with increased recruitment of p300 to several genes including transcription factors, increased acetylation of specific lysines in histones and transcription factors, altered chromatin organization, and increased hypertrophic and fibrogenic gene expression. Cardiac hypertrophy and myocardial fibrogenesis are common pathological manifestations of several stress-induced accelerated cardiac aging-related pathologies, including high blood pressure-induced or environmentally induced cardiac hypertrophy, myocardial infarction, diabetes-induced cardiomyopathy, and heart failure. Numerous studies using cellular and animal models clearly indicate that pharmacologic or genetic normalization of p300 activity has the potential to prevent or halt the progression of cardiac aging pathologies. Based on these preclinical studies, development of safe, non-toxic, small molecule inhibitors/epidrugs targeting p300 is an ideal approach to control accelerated cardiac aging-related deaths worldwide.
Copyright: © 2020 Ghosh et al.
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