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1.
J Cardiovasc Magn Reson ; 22(1): 63, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32892751

RESUMO

BACKGROUND: Myocardial native T1 and T2 relaxation time mapping are sensitive to pathological increase of myocardial water content (e.g. myocardial edema). However, the influence of physiological hydration changes as a possible confounder of relaxation time assessment has not been studied. The purpose of this study was to evaluate, whether changes in myocardial water content due to dehydration and hydration might alter myocardial relaxation times in healthy subjects. METHODS: A total of 36 cardiovascular magnetic resonance (CMR) scans were performed in 12 healthy subjects (5 men, 25.8 ± 3.2 years). Subjects underwent three successive CMR scans: (1) baseline scan, (2) dehydration scan after 12 h of fasting (no food or water), (3) hydration scan after hydration. CMR scans were performed for the assessment of myocardial native T1 and T2 relaxation times and cardiac function. For multiple comparisons, repeated measures ANOVA or the Friedman test was used. RESULTS: There was no change in systolic blood pressure or left ventricular ejection fraction between CMR scans (P > 0.05, respectively). T1 relaxation times were significantly reduced with dehydration (987 ± 27 ms [baseline] vs. 968 ± 29 ms [dehydration] vs. 986 ± 28 ms [hydration]; P = 0.006). Similar results were observed for T2 relaxation times (52.9 ± 1.8 ms [baseline] vs. 51.5 ± 2.0 ms [dehydration] vs. 52.2 ± 1.9 ms [hydration]; P = 0.020). CONCLUSIONS: Dehydration may lead to significant alterations in relaxation times and thereby may influence precise, repeatable and comparable assessment of native T1 and T2 relaxation times. Hydration status should be recognized as new potential confounder of native T1 and T2 relaxation time assessment in clinical routine.


Assuntos
Composição Corporal , Coração/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Estado de Hidratação do Organismo , Função Ventricular Esquerda , Equilíbrio Hidroeletrolítico , Adulto , Desidratação , Diástole , Feminino , Voluntários Saudáveis , Coração/fisiologia , Humanos , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , Adulto Jovem
2.
Life Sci ; 259: 118377, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32898526

RESUMO

The endothelium is the innermost vascular lining performing significant roles all over the human body while maintaining the blood pressure at physiological levels. Malfunction of endothelium is thus recognized as a biomarker linked with many vascular diseases including but not limited to atherosclerosis, hypertension and thrombosis. Alternatively, prevention of endothelial malfunctioning or regulating the functions of its associated physiological partners like endothelial nitric oxide synthase can prevent the associated vascular disorders which account for the highest death toll worldwide. While many anti-hypertensive drugs are available commercially, a comprehensive description of the key physiological roles of the endothelium and its regulation by endothelial nitric oxide synthase or vice versa is the need of the hour to understand its contribution in vascular homeostasis. This, in turn, will help in designing new therapeutics targeting endothelial nitric oxide synthase or its interacting partners present in the cellular pool. This review describes the central role of vascular endothelium in the regulation of endothelial nitric oxide synthase while outlining the emerging drug targets present in the vasculature with potential to treat vascular disorders including hypertension.


Assuntos
Pressão Sanguínea/fisiologia , Endotélio Vascular/fisiologia , Coração/fisiologia , Óxido Nítrico Sintase Tipo III/metabolismo , Animais , Endotélio Vascular/metabolismo , Humanos
3.
Nat Commun ; 11(1): 4283, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32883967

RESUMO

Our understanding of the spatiotemporal regulation of cardiogenesis is hindered by the difficulties in modeling this complex organ currently by in vitro models. Here we develop a method to generate heart organoids from mouse embryonic stem cell-derived embryoid bodies. Consecutive morphological changes proceed in a self-organizing manner in the presence of the laminin-entactin (LN/ET) complex and fibroblast growth factor 4 (FGF4), and the resulting in vitro heart organoid possesses atrium- and ventricle-like parts containing cardiac muscle, conducting tissues, smooth muscle and endothelial cells that exhibited myocardial contraction and action potentials. The heart organoids exhibit ultrastructural, histochemical and gene expression characteristics of considerable similarity to those of developmental hearts in vivo. Our results demonstrate that this method not only provides a biomimetic model of the developing heart-like structure with simplified differentiation protocol, but also represents a promising research tool with a broad range of applications, including drug testing.


Assuntos
Matriz Extracelular/metabolismo , Fator 4 de Crescimento de Fibroblastos/metabolismo , Coração , Células-Tronco Embrionárias Murinas/metabolismo , Organoides , Potenciais de Ação , Diamino Aminoácidos/metabolismo , Animais , Biomimética/métodos , Diferenciação Celular , Linhagem Celular , Células Endoteliais , Coração/crescimento & desenvolvimento , Coração/fisiologia , Glicoproteínas de Membrana/metabolismo , Camundongos , Contração Miocárdica , Miocárdio , Organoides/citologia , Organoides/crescimento & desenvolvimento , Organoides/ultraestrutura
4.
Medicine (Baltimore) ; 99(30): e21302, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791715

RESUMO

INTRODUCTION: By detecting the metabolic difference of the Heart and Lung meridians, the present study aims to investigate the specificity of different meridians and verify whether functional near infrared spectroscopy is validated as an add-on technique to assist diagnosis of chronic obstructive pulmonary disease (COPD). METHODS AND ANALYSIS: The Lung and Heart meridians are chosen as the target for comparison; accordingly, 120 eligible participants will be included and divided into the COPD group, healthy control group, and healthy intervention group. Functional near infrared spectroscopy will be adopted to measure the metabolic characteristics of the Heart and Lung meridians. On one hand, the specificity of the meridian-visceral association will be investigated by comparing the metabolic difference in the Heart and Lung meridians between the healthy control group and COPD group. On the other hand, the specificity of site-to-site association will be determined by comparing the metabolic change between the 2 meridians that induced by moxibustion in the Heart meridian and Lung meridian, respectively, in the healthy control group. The primary outcome will be regional oxygen saturation of corresponding regions along the Heart and Lung meridians. TRIAL REGISTRATION: ClinicalTrials.gov NCT04046666.


Assuntos
Coração/fisiologia , Pulmão/metabolismo , Moxibustão/métodos , Doença Pulmonar Obstrutiva Crônica/terapia , Espectrofotometria Infravermelho/métodos , Pontos de Acupuntura , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Voluntários Saudáveis , Humanos , Masculino , Meridianos , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Oxigênio/metabolismo , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Sensibilidade e Especificidade
5.
PLoS One ; 15(8): e0231234, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32804947

RESUMO

Cardiometabolic syndrome has become a global health issue. Heart failure is a common comorbidity of cardiometabolic syndrome. Successful drug development to prevent cardiometabolic syndrome and associated comorbidities requires preclinical models predictive of human conditions. To characterize the heart failure component of cardiometabolic syndrome, cardiometabolic, metabolic, and renal biomarkers were evaluated in lean and obese ZSF1 19- to 32-week-old male rats. Histopathological assessment of kidneys and hearts was performed. Cardiac function, exercise capacity, and left ventricular gene expression were also analyzed. Obese ZSF1 rats exhibited multiple features of human cardiometabolic syndrome by pathological changes in systemic renal, metabolic, and cardiovascular disease circulating biomarkers. Hemodynamic assessment, echocardiography, and decreased exercise capacity confirmed heart failure with preserved ejection fraction. RNA-seq results demonstrated changes in left ventricular gene expression associated with fatty acid and branched chain amino acid metabolism, cardiomyopathy, cardiac hypertrophy, and heart failure. Twelve weeks of growth differentiation factor 15 (GDF15) treatment significantly decreased body weight, food intake, blood glucose, and triglycerides and improved exercise capacity in obese ZSF1 males. Systemic cardiovascular injury markers were significantly lower in GDF15-treated obese ZSF1 rats. Obese ZSF1 male rats represent a preclinical model for human cardiometabolic syndrome with established heart failure with preserved ejection fraction. GDF15 treatment mediated dietary response and demonstrated a cardioprotective effect in obese ZSF1 rats.


Assuntos
Fator 15 de Diferenciação de Crescimento/metabolismo , Fator 15 de Diferenciação de Crescimento/farmacologia , Síndrome Metabólica/metabolismo , Animais , Biomarcadores/metabolismo , Coração/fisiologia , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/fisiopatologia , Rim/metabolismo , Masculino , Síndrome Metabólica/complicações , Miocárdio/metabolismo , Obesidade/complicações , Ratos , Ratos Endogâmicos , Ratos Zucker , Volume Sistólico/fisiologia , Função Ventricular Esquerda/efeitos dos fármacos , Função Ventricular Esquerda/fisiologia
6.
Nature ; 584(7822): 589-594, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32814899

RESUMO

The inner surfaces of the human heart are covered by a complex network of muscular strands that is thought to be a remnant of embryonic development1,2. The function of these trabeculae in adults and their genetic architecture are unknown. Here we performed a genome-wide association study to investigate image-derived phenotypes of trabeculae using the fractal analysis of trabecular morphology in 18,096 participants of the UK Biobank. We identified 16 significant loci that contain genes associated with haemodynamic phenotypes and regulation of cytoskeletal arborization3,4. Using biomechanical simulations and observational data from human participants, we demonstrate that trabecular morphology is an important determinant of cardiac performance. Through genetic association studies with cardiac disease phenotypes and Mendelian randomization, we find a causal relationship between trabecular morphology and risk of cardiovascular disease. These findings suggest a previously unknown role for myocardial trabeculae in the function of the adult heart, identify conserved pathways that regulate structural complexity and reveal the influence of the myocardial trabeculae on susceptibility to cardiovascular disease.


Assuntos
Doenças Cardiovasculares/genética , Fractais , Predisposição Genética para Doença , Coração/anatomia & histologia , Coração/fisiologia , Miocárdio/metabolismo , Adulto , Idoso , Animais , Doenças Cardiovasculares/fisiopatologia , Citoesqueleto/genética , Citoesqueleto/fisiologia , Técnicas de Inativação de Genes , Loci Gênicos/genética , Estudo de Associação Genômica Ampla , Coração/embriologia , Hemodinâmica , Humanos , Pessoa de Meia-Idade , Miocárdio/citologia , Oryzias/embriologia , Oryzias/genética , Fenótipo
7.
Gene ; 761: 145039, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-32777527

RESUMO

The wood frog (Rana sylvatica) can tolerate full body freezing in winter. As a protective response, wood frogs dehydrate their cells and accumulate large quantities of glucose as an intracellular cryoprotectant. Freezing causes ischemia since blood delivery to organs is interrupted. Fascinatingly, wood frogs can tolerate dehydration, extreme hyperglycemia, and anoxia independently of freezing. In response to low oxygen levels, wood frogs strategically reduce their metabolic rates and allocate the finite amount of intracellular fuel available to pro-survival processes while reducing or interrupting all others. In this study, the involvement of advanced glycation end products (AGEs) and the high mobility group box 1 (HMGB1) protein in activating RAGE (AGE receptor) were investigated. The results show that freezing, anoxia and dehydration induced the expression of total HMGB1 and its acetylation in the heart. RAGE levels were induced in response to all stress conditions, which resulted in differential regulation of the ETS1 transcription factor. While the nuclear localization of total ETS1 was not affected, the DNA binding activity of total and its active form increased in response to freezing and dehydration but not in response to anoxia. Current results indicate that ETS1 acts as a transcriptional activator for peroxiredoxin 1 in response to freezing but acts as a transcriptional repressor of several nuclear-encoded mitochondrial genes in response to all stresses. Altogether, current results show that the HMGB1/RAGE axis may activate ETS1 and that this activation could result in both transcriptional activation and/or repression in a stress-dependent manner.


Assuntos
Mitocôndrias/metabolismo , Miocárdio/metabolismo , Ranidae/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Animais , Desidratação/metabolismo , Congelamento , Glucose/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Produtos Finais de Glicação Avançada/fisiologia , Proteína HMGB1/metabolismo , Proteína HMGB1/fisiologia , Coração/fisiologia , Hipóxia/metabolismo , Oxigênio/metabolismo , Ranidae/genética , Receptor para Produtos Finais de Glicação Avançada/fisiologia , Estresse Fisiológico/fisiologia
8.
Phys Rev Lett ; 125(5): 058102, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32794888

RESUMO

Animal hearts are soft shells that actively pump blood to oxygenate tissues. Here, we propose an allometric scaling law for the heart rate based on the idea of elastohydrodynamic resonance of a fluid-loaded soft active elastic shell that buckles and contracts axially when twisted periodically. We show that this picture is consistent with numerical simulations of soft cylindrical shells that twist-buckle while pumping a viscous fluid, yielding optimum ejection fractions of 35%-40% when driven resonantly. Our scaling law is consistent with experimental measurements of heart rates over 2 orders of magnitude, and provides a mechanistic basis for how metabolism scales with organism size. In addition to providing a physical rationale for the heart rate and metabolism of an organism, our results suggest a simple design principle for soft fluidic pumps.


Assuntos
Frequência Cardíaca/fisiologia , Coração/anatomia & histologia , Coração/fisiologia , Modelos Cardiovasculares , Animais , Simulação por Computador , Elasticidade , Ventrículos do Coração/anatomia & histologia , Hidrodinâmica , Função Ventricular
9.
Life Sci ; 259: 118187, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32781061

RESUMO

AIMS: Voluntary exercise training has cardioprotective effects in humans, but the underlying mechanism is unknown. This research was done to estimate the effect of voluntary exercise training to attenuate middle-aged maturity-induced cardiac apoptosis. MATERIALS AND METHODS: The study was designed to divide 64 male mice randomly into four groups, consisting of a 9-month sedentary pre-middle-aged group (9M), 15-month sedentary middle-aged group (15M), and two exercise groups using a voluntary wheel running respectively (9M+EX, 15M+EX). After 3 months, the condition of cardiac apoptosis in different groups was measured by HE dying, TUNEL and DAPI staining, and Western Blot analysis. KEY FINDINGS: TUNEL-positive cells were increased in 15M group compared with 9M group, while decreased in 9M+EX and 15M+EX groups compared with their control groups respectively. Protein levels of AIF, Endo G, TNF-α, TNFR1, TRAF2, TRADD, Fas, FasL, FADD, activated caspase 8, 3, 9, Bax/Bcl2, Bak/BclxL, and tBid were decreased in 9M+EX and 15M+EX groups compared with their control groups respectively. The protein levels of pBad/Bad, 14-3-3, IGF1, IGFR1, pPI3K/PI3K, and pAKT/AKT were more activated in the 9M+EX and 15M+EX groups than those in their control groups respectively. Significant differences were found between 9M group and 15M group for the protein levels of TRAF2, FADD, Bax/Bcl2, tBid and pAKT/AKT. SIGNIFICANCE: Voluntary exercise training as an important lifestyle modification may prevent cardiac widely dispersed apoptosis and enhance cardiac survival at middle-aged maturity.


Assuntos
Envelhecimento/fisiologia , Apoptose/fisiologia , Coração/fisiologia , Condicionamento Físico Animal/fisiologia , Animais , Marcação In Situ das Extremidades Cortadas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias Cardíacas/fisiologia , Músculo Esquelético/citologia , Músculo Esquelético/fisiologia , Corrida/fisiologia , Comportamento Sedentário
10.
Int J Nanomedicine ; 15: 4205-4224, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606673

RESUMO

Cardiovascular diseases are the number one cause of heart failure and death in the world, and the transplantation of the heart is an effective and viable choice for treatment despite presenting many disadvantages (most notably, transplant heart availability). To overcome this problem, cardiac tissue engineering is considered a promising approach by using implantable artificial blood vessels, injectable gels, and cardiac patches (to name a few) made from biodegradable polymers. Biodegradable polymers are classified into two main categories: natural and synthetic polymers. Natural biodegradable polymers have some distinct advantages such as biodegradability, abundant availability, and renewability but have some significant drawbacks such as rapid degradation, insufficient electrical conductivity, immunological reaction, and poor mechanical properties for cardiac tissue engineering. Synthetic biodegradable polymers have some advantages such as strong mechanical properties, controlled structure, great processing flexibility, and usually no immunological concerns; however, they have some drawbacks such as a lack of cell attachment and possible low biocompatibility. Some applications have combined the best of both and exciting new natural/synthetic composites have been utilized. Recently, the use of nanostructured polymers and polymer nanocomposites has revolutionized the field of cardiac tissue engineering due to their enhanced mechanical, electrical, and surface properties promoting tissue growth. In this review, recent research on the use of biodegradable natural/synthetic nanocomposite polymers in cardiac tissue engineering is presented with forward looking thoughts provided for what is needed for the field to mature.


Assuntos
Materiais Biocompatíveis/química , Coração/fisiologia , Nanocompostos/química , Nanomedicina , Polímeros/química , Engenharia Tecidual/métodos , Animais , Humanos , Nanocompostos/ultraestrutura
11.
Nature ; 582(7811): 271-276, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32499640

RESUMO

A major factor in the progression to heart failure in humans is the inability of the adult heart to repair itself after injury. We recently demonstrated that the early postnatal mammalian heart is capable of regeneration following injury through proliferation of preexisting cardiomyocytes1,2 and that Meis1, a three amino acid loop extension (TALE) family homeodomain transcription factor, translocates to cardiomyocyte nuclei shortly after birth and mediates postnatal cell cycle arrest3. Here we report that Hoxb13 acts as a cofactor of Meis1 in postnatal cardiomyocytes. Cardiomyocyte-specific deletion of Hoxb13 can extend the postnatal window of cardiomyocyte proliferation and reactivate the cardiomyocyte cell cycle in the adult heart. Moreover, adult Meis1-Hoxb13 double-knockout hearts display widespread cardiomyocyte mitosis, sarcomere disassembly and improved left ventricular systolic function following myocardial infarction, as demonstrated by echocardiography and magnetic resonance imaging. Chromatin immunoprecipitation with sequencing demonstrates that Meis1 and Hoxb13 act cooperatively to regulate cardiomyocyte maturation and cell cycle. Finally, we show that the calcium-activated protein phosphatase calcineurin dephosphorylates Hoxb13 at serine-204, resulting in its nuclear localization and cell cycle arrest. These results demonstrate that Meis1 and Hoxb13 act cooperatively to regulate cardiomyocyte maturation and proliferation and provide mechanistic insights into the link between hyperplastic and hypertrophic growth of cardiomyocytes.


Assuntos
Calcineurina/metabolismo , Proliferação de Células , Proteínas de Homeodomínio/metabolismo , Proteína Meis1/metabolismo , Miócitos Cardíacos/citologia , Animais , Animais Recém-Nascidos , Feminino , Deleção de Genes , Regulação da Expressão Gênica , Coração/fisiologia , Proteínas de Homeodomínio/genética , Masculino , Camundongos , Miocárdio/citologia , Ligação Proteica , Regeneração
12.
PLoS One ; 15(6): e0233264, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32479554

RESUMO

The dogs' responses to training exercise are seldom monitored using physiological variables, and cardiac autonomic regulation (CAR) is a relevant determinant of endurance-training adaptation. There are studies in the literature establishing that regular exercise could interfere with CAR in dogs, measured by heart rate and vagal-derived indexes of heart-rate-variability (HRV). However, few studies were found using a prescribed training program based on the lactate threshold (LT) to determine HRV by a 24-h Holter analysis. The purpose of this study was to test whether an endurance-training program (ETP) guided individually by LT raises time-domain measures of HRV in healthy Beagle dogs. Twenty dogs were assigned to two groups: control (C) and trained (T). The dogs from group T underwent an incremental exercise test (IET) to determine their LT. Both LT and velocity corresponding to the LT (VLT) was determined by visual inspection. T group performed an eight-week endurance-training program consisting of treadmill runs set to 70-80% of the VLT. Next, dogs from the group T have submitted to IET again. The maximal velocities (Vmax) at which achieved by the trained dogs in both IETs were determined. The group S did not undergo IETs or ETP. HRV was determined by the 24-hour-Holter at rest, before and on the 2°, 4°, 6° and 8° training weeks. To examine the HR impact on HRV, standard HRV variables were normalized to prevailing HR. VLT and Vmax rose in group T, indicating an improvement of dogs' aerobic and anaerobic capacity. The normalized standard HRV indexes were relatively attenuated since these variables had a reduction in the degree of correlation concerning an average HR. The ETP resulted in decreased resting heart rate and increased time-domain indices, highlighting the log-transformed square root of the mean sum of the squared differences between R-R intervals (Ln rMSSD). The lactate-guided endurance-training program could lead to better parasympathetic cardiac modulation in Beagle dogs.


Assuntos
Frequência Cardíaca/fisiologia , Ácido Láctico/metabolismo , Condicionamento Físico Animal/métodos , Animais , Sistema Nervoso Autônomo/fisiologia , Cães , Eletrocardiografia Ambulatorial/métodos , Eletrocardiografia Ambulatorial/veterinária , Treino Aeróbico/métodos , Teste de Esforço , Feminino , Coração/fisiologia , Masculino , Resistência Física/fisiologia , Nervo Vago/fisiologia
13.
PLoS Genet ; 16(6): e1008778, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32579604

RESUMO

Endurance exercise has broadly protective effects across organisms, increasing metabolic fitness and reducing incidence of several age-related diseases. Drosophila has emerged as a useful model for studying changes induced by chronic endurance exercise, as exercising flies experience improvements to various aspects of fitness at the cellular, organ and organismal level. The activity of octopaminergic neurons is sufficient to induce the conserved cellular and physiological changes seen following endurance training. All 4 octopamine receptors are required in at least one target tissue, but only one, Octß1R, is required for all of them. Here, we perform tissue- and adult-specific knockdown of alpha- and beta-adrenergic octopamine receptors in several target tissues. We find that reduced expression of Octß1R in adult muscles abolishes exercise-induced improvements in endurance, climbing speed, flight, cardiac performance and fat-body catabolism in male Drosophila. Importantly, Octß1R and OAMB expression in the heart is also required cell-nonautonomously for adaptations in other tissues, such as skeletal muscles in legs and adult fat body. These findings indicate that activation of distinct octopamine receptors in skeletal and cardiac muscle are required for Drosophila exercise adaptations, and suggest that cell non-autonomous factors downstream of octopaminergic activation play a key role.


Assuntos
Adaptação Fisiológica , Proteínas de Drosophila/metabolismo , Voo Animal , Coração/fisiologia , Músculo Esquelético/metabolismo , Miocárdio/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Receptores de Neurotransmissores/metabolismo , Animais , Drosophila , Proteínas de Drosophila/genética , Corpo Adiposo/metabolismo , Músculo Esquelético/fisiologia , Receptores Acoplados a Proteínas-G/genética , Receptores de Neurotransmissores/genética
14.
Zhongguo Zhen Jiu ; 40(6): 635-9, 2020 Jun 12.
Artigo em Chinês | MEDLINE | ID: mdl-32538016

RESUMO

OBJECTIVE: To observe the effects of electroacupuncture (EA) pretreatment on the cardiac ejection fraction (EF), the number of macrophages in spleen and heart, and the expression of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) and interleukin-1ß (IL-1ß) in myocardium in mice with acute myocardial ischemia, and to explore the possible mechanism of EA pretreatment on promoting myocardial protection. METHODS: A total of 30 male C57BL/6J mice were randomly divided into a control group, a model group and an EA pretreatment group, 10 rats in each group. The acute myocardial ischemia model was established by ligating the left anterior descending branch of the coronary artery in the model group and EA pretreatment group, while threading but no ligating at left anterior descending branch of the coronary artery was applied in the control group. In the EA pretreatment group, mice were intervented with EA at bilateral "Neiguan" (PC 6), disperse-dense wave, frequency of 2 Hz/15 Hz, intensity of 2 mA; each EA treatment last for 20 min, once a day, and 3-day treatment was given before model establishment. The EF value was evaluated by ultrasonic cardiogram; the number of macrophages in spleen and heart was measured by flow cytometry; the expression level of NLRP3 and IL-1ß in myocardium was measured by Western blot. RESULTS: Compared with the control group, the EF value was decreased in the model group (P<0.001), the number of macrophages in the heart and spleen was increased (P<0.001), and the expression level of NLRP3 and IL-1ß in the myocardium was increased (P<0.001, P<0.01). Compared with the model group, the EF value was increased in the EA pretreatment group (P<0.01), the number of macrophages in the heart and spleen was decreased (P<0.01), and the expression level of NLRP3 and IL-1ß in the myocardium was decreased (P<0.01, P<0.05). CONCLUSION: EA pretreatment could reduce the number of macrophages in spleen and heart, down-regulate the expression of NLRP3 and IL-1ß in myocardial tissue in mice with acute myocardial ischemia, which could relieve the local inflammatory response and achieve the myocardial protective effect.


Assuntos
Eletroacupuntura , Coração/fisiologia , Inflamação/imunologia , Isquemia Miocárdica/terapia , Pontos de Acupuntura , Animais , Interleucina-1beta/metabolismo , Macrófagos/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Isquemia Miocárdica/imunologia , Miocárdio , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Distribuição Aleatória , Baço
15.
PLoS One ; 15(6): e0234340, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32579587

RESUMO

The experimental quantification and modeling of the multiaxial mechanical response of polymer membranes of coronary balloon catheters have not yet been carried out. Due to the lack of insights, it is not shown whether isotropic material models can describe the material response of balloon catheter membranes expanded with nominal or higher, supra-nominal pressures. Therefore, for the first time, specimens of commercial polyamide-12 balloon catheters membranes were investigated during uniaxial and biaxial loading scenarios. Furthermore, the influence of kinematic effects on the material response was observed by comparing results from quasi-static and dynamic biaxial extension tests. Novel clamping techniques are described, which allow to test even tiny specimens taken from the balloon membranes. The results of this study reveal the semi-compliant, nonlinear, and viscoelastic character of polyamide-12 balloon catheter membranes. Above nominal pressure, the membranes show a pronounced anisotropic mechanical behavior with a stiffer response in the circumferential direction. The anisotropic feature intensifies with an increasing strain-rate. A modified polynomial model was applied to represent the realistic mechanical response of the balloon catheter membranes during dynamic biaxial extension tests. This study also includes a compact set of constitutive model parameters for the use of the proposed model in future finite element analyses to perform more accurate simulations of expanding balloon catheters.


Assuntos
Angioplastia Coronária com Balão/instrumentação , Angioplastia Coronária com Balão/métodos , Nylons/química , Anisotropia , Fenômenos Biomecânicos/fisiologia , Cateteres Cardíacos/tendências , Análise de Elementos Finitos , Coração/fisiologia , Membranas/metabolismo , Modelos Biológicos , Miocárdio/metabolismo , Nylons/farmacologia , Estresse Mecânico , Resistência à Tração/fisiologia
16.
Artigo em Inglês | MEDLINE | ID: mdl-32485990

RESUMO

Irisin, a recently identified myokine, plays an important physiological role in modulating energy homeostasis. However, the role of irisin in cardiac function during exercise has not been evaluated. In this study, we investigated the effect of exercise on irisin, pro-inflammatory cytokines, and cardiac function during 12 weeks of exercise in rats. Eight-week-old Sprague-Dawley male rats were randomly divided into two groups (n = 9 per group): sedentary control (CON) and exercise (EXE) groups. The EXE group was trained on a motorized treadmill at 20 m/min, for 60 min/day, five times/week for 12 weeks. The EXE group showed a decrease in abdominal visceral fat (p < 0.05), epididymal fat (p < 0.01), and total cholesterol (TC) (p < 0.05) and an increase in irisin levels (p < 0.01). Irisin negatively correlated with abdominal visceral (p < 0.05) and epididymal fat (p < 0.05) and positively correlated with the ejection fraction (p < 0.05), fractional shortening (p < 0.05), and cardiac output (p < 0.05). In conclusion, exercise decreases the abdominal visceral and epididymal fat and TC levels, possibly caused by elevated irisin levels, thus improving the cardiac function. This suggests that exercise-induced circulating irisin levels correlate with improved cardiac function in rats.


Assuntos
Fibronectinas , Coração , Condicionamento Físico Animal , Animais , Fibronectinas/metabolismo , Coração/fisiologia , Masculino , Ratos , Ratos Sprague-Dawley , Fatores de Transcrição
17.
Adv Gerontol ; 33(1): 127-130, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32362095

RESUMO

Presents the results of a dynamic integrated study of the vegetative, metabolic and psycho-physiological components of the functional state of elderly hockey players before and after participating in competitions. The study involved 42 male hockey players aged 55-64 years. It has been established that the indicators of the vegetative regulation of cardiac activity are the most stable component of the functional state in the group of elderly athletes. At the same time, after participating in competitions, a statistically significant decrease in the simple sensorimotor response and an increase in lipid peroxidation processes were revealed. It is proved that the use of therapeutic regulators of the functional state (in particular, pharmaco-, psycho- and physiotherapeutic) should be directed to the components of the central nervous system and the antioxidant defense system, as the most sensitive and susceptible to suffering.


Assuntos
Atletas , Hóquei , Aptidão Física , Idoso , Antioxidantes , Coração/fisiologia , Humanos , Peroxidação de Lipídeos , Masculino , Pessoa de Meia-Idade , Córtex Sensório-Motor/fisiologia
18.
PLoS One ; 15(5): e0231695, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32392258

RESUMO

We present a novel modification of genetic algorithm (GA) which determines personalized parameters of cardiomyocyte electrophysiology model based on set of experimental human action potential (AP) recorded at different heart rates. In order to find the steady state solution, the optimized algorithm performs simultaneous search in the parametric and slow variables spaces. We demonstrate that several GA modifications are required for effective convergence. Firstly, we used Cauchy mutation along a random direction in the parametric space. Secondly, relatively large number of elite organisms (6-10% of the population passed on to new generation) was required for effective convergence. Test runs with synthetic AP as input data indicate that algorithm error is low for high amplitude ionic currents (1.6±1.6% for IKr, 3.2±3.5% for IK1, 3.9±3.5% for INa, 8.2±6.3% for ICaL). Experimental signal-to-noise ratio above 28 dB was required for high quality GA performance. GA was validated against optical mapping recordings of human ventricular AP and mRNA expression profile of donor hearts. In particular, GA output parameters were rescaled proportionally to mRNA levels ratio between patients. We have demonstrated that mRNA-based models predict the AP waveform dependence on heart rate with high precision. The latter also provides a novel technique of model personalization that makes it possible to map gene expression profile to cardiac function.


Assuntos
Potenciais de Ação , Coração/fisiologia , Miócitos Cardíacos/fisiologia , Potenciais de Ação/genética , Potenciais de Ação/fisiologia , Expressão Gênica , Transplante de Coração , Ventrículos do Coração/metabolismo , Humanos , Modelos Biológicos , Técnicas de Patch-Clamp , RNA-Seq , Doadores de Tecidos
19.
J Vis Exp ; (158)2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32364545

RESUMO

It has been shown that endocardial endothelial cells (EECs) and coronary endothelial cells (CECs) differ in origin, development, markers, and functions. Consequently, these two cell populations play unique roles in cardiac diseases. Current studies involving isolated endothelial cells investigate cell populations consisting of both EECs and CECs. This protocol outlines a method to independently isolate these two cell populations for cell-specific characterization. Following the collection of the left and right ventricular free wall, endothelial cells from the outer surface and inner surface are separately liberated using a digestion buffer solution. The sequential digestion of the outer surface and the inner endocardial layer retained separation of the two endothelial cell populations. The separate isolation of EECs and CECs is further verified through the identification of markers specific to each population. Based on previously published single cell RNA profiling in the mouse heart, the Npr3, Hapln1, and Cdh11 gene expression is unique to EECs; while Fabp4, Mgll, and Cd36 gene expression is unique to CECs. qPCR data revealed enriched expression of these characteristic markers in their respective samples, indicating successful EEC and CEC isolation, as well as maintenance of cell phenotype, enabling further cell-specific functional analysis.


Assuntos
Vasos Coronários/citologia , Endocárdio/citologia , Endotélio Vascular/citologia , Ventrículos do Coração/citologia , Coração/fisiologia , Animais , Biomarcadores/metabolismo , Células Cultivadas , Vasos Coronários/metabolismo , Endocárdio/metabolismo , Endotélio Vascular/metabolismo , Perfilação da Expressão Gênica , Ventrículos do Coração/metabolismo , Ratos , Ratos Sprague-Dawley
20.
Artigo em Inglês | MEDLINE | ID: mdl-32383995

RESUMO

Protein kinases play an integral role in cardiac development, function, and disease. Recent experimental and clinical data have implied that protein kinases belonging to a family of atypical α-protein kinases, including α-protein kinase 2 (ALPK2), are important for regulating cardiac development and maintaining function via regulation of WNT signaling. A recent study in zebrafish reported that loss of ALPK2 leads to severe cardiac defects; however, the relevance of ALPK2 has not been studied in a mammalian animal model. To assess the role of ALPK2 in the mammalian heart, we generated two independent global Alpk2-knockout (Alpk2-gKO) mouse lines, using CRISPR/Cas9 technology. We performed physiological and biochemical analyses of Alpk2-gKO mice to determine the functional, morphological, and molecular consequences of Alpk2 deletion at the organismal level. We found that Alpk2-gKO mice exhibited normal cardiac function and morphology up to one year of age. Moreover, we did not observe altered WNT signaling in neonatal Alpk2-gKO mouse hearts. In conclusion, Alpk2 is dispensable for cardiac development and function in the murine model. Our results suggest that Alpk2 is a rapidly evolving gene that lost its essential cardiac functions in mammals.NEW & NOTEWORTHY Several studies indicated the importance of ALPK2 for cardiac function and development. A recent study in zebrafish report that loss of ALPK2 leads to severe cardiac defects. In contrast, murine Alpk2-gKO models developed in this work display no overt cardiac phenotype. Our results suggest ALPK2, as a rapidly evolving gene, lost its essential cardiac functions in mammals.


Assuntos
Coração/crescimento & desenvolvimento , Miocárdio/metabolismo , Proteínas Quinases/genética , Animais , Coração/fisiologia , Camundongos , Camundongos Knockout , Miócitos Cardíacos/metabolismo , Proteínas Quinases/metabolismo
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