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Chinese Medical Journal ; (24): 837-848, 2022.
Article in English | WPRIM | ID: wpr-927571


BACKGROUND@#Pulmonary microvascular endothelial cells (PMVECs) were not complex, and the endothelial barrier was destroyed in the pathogenesis progress of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Previous studies have demonstrated that hepatocyte growth factor (HGF), which was secreted by bone marrow mesenchymal stem cells, could decrease endothelial apoptosis. We investigated whether mTOR/STAT3 signaling acted in HGF protective effects against oxidative stress and mitochondria-dependent apoptosis in lipopolysaccharide (LPS)-induced endothelial barrier dysfunction and ALI mice.@*METHODS@#In our current study, we introduced LPS-induced PMEVCs with HGF treatment. To investigate the effects of mammalian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3) pathway in endothelial oxidative stress and mitochondria-dependent apoptosis, mTOR inhibitor rapamycin and STAT3 inhibitor S3I-201 were, respectively, used to inhibit mTOR/STAT3 signaling. Moreover, lentivirus vector-mediated mTORC1 (Raptor) and mTORC2 (Rictor) gene knockdown modifications were introduced to evaluate mTORC1 and mTORC1 pathways. Calcium measurement, reactive oxygen species (ROS) production, mitochondrial membrane potential and protein, cell proliferation, apoptosis, and endothelial junction protein were detected to evaluate HGF effects. Moreover, we used the ALI mouse model to observe the mitochondria pathological changes with an electron microscope in vivo.@*RESULTS@#Our study demonstrated that HGF protected the endothelium via the suppression of ROS production and intracellular calcium uptake, which lead to increased mitochondrial membrane potential (JC-1 and mitochondria tracker green detection) and specific proteins (complex I), raised anti-apoptosis Messenger Ribonucleic Acid level (B-cell lymphoma 2 and Bcl-xL), and increased endothelial junction proteins (VE-cadherin and occludin). Reversely, mTOR inhibitor rapamycin and STAT3 inhibitor S3I-201 could raise oxidative stress and mitochondria-dependent apoptosis even with HGF treatment in LPS-induced endothelial cells. Similarly, mTORC1 as well as mTORC2 have the same protective effects in mitochondria damage and apoptosis. In in vivo experiments of ALI mouse, HGF also increased mitochondria structural integrity via the mTOR/STAT3 pathway.@*CONCLUSION@#In all, these reveal that mTOR/STAT3 signaling mediates the HGF suppression effects to oxidative level, mitochondria-dependent apoptosis, and endothelial junction protein in ARDS, contributing to the pulmonary endothelial survival and barrier integrity.

Animals , Apoptosis , Calcium/metabolism , Endothelial Cells/metabolism , Endothelium/metabolism , Hepatocyte Growth Factor/metabolism , Lipopolysaccharides/pharmacology , Mammals/metabolism , Mechanistic Target of Rapamycin Complex 1/metabolism , Mechanistic Target of Rapamycin Complex 2/metabolism , Mice , Mitochondria/metabolism , Oxidative Stress , Reactive Oxygen Species/metabolism , Respiratory Distress Syndrome, Newborn , Sirolimus/pharmacology , TOR Serine-Threonine Kinases/metabolism
Braz. J. Pharm. Sci. (Online) ; 58: e191010, 2022. tab
Article in English | LILACS | ID: biblio-1384021


To compare global endothelial function assessed by pulse wave analysis (PWA) using the ratio of endothelium dependent vasodilatation (EDV) to endothelium independent vasodilatation (EIV) in patients with hypercholesterolemia and controls. 92 subjects [46 hypercholesterolemics, 46 controls] were studied at standardized conditions. Baseline augmentation index (AIx) was assessed followed by the administration of 0.5 mg sublingual nitroglycerine, an endothelium independent vasodilator. AIx was assessed and the maximum change in AIx after nitroglycerine was recorded as EIV. After a washout period of 30 minutes, 400 µg of inhaled salbutamol, an endothelium dependent vasodilator was administered. AIx was assessed again and the maximum change in AIx after salbutamol was recorded as EDV. Global endothelial function was calculated as EDV:EIV ratio. EDV and EIV in patients with hypercholesterolemia compared to controls were 2.97 ± 3.95 and 6.65 ± 3.80 (p<0.001); and 13.41 ± 4.57 and 15.88 ± 4.78 (p=0.01) respectively. EDV:EIV ratio was significantly reduced in patients with hypercholesterolemia compared to controls; 0.21 ± 0.38 and 0.44 ± 0.24 (p<0.001) respectively. EDV:EIV ratio was significantly reduced in patients with hypercholesterolemia compared to controls. PWA is a potential clinical tool to assess global endothelial function in patients with hypercholesterole

Humans , Male , Female , Adult , Endothelium/metabolism , Pulse Wave Analysis/methods , Hypercholesterolemia , Patients , Vasodilator Agents/adverse effects
Rev. cuba. med ; 60(3): e1661, 2021.
Article in Spanish | LILACS, CUMED | ID: biblio-1347503


Hemos leído con gran atención el artículo de los autores González Rey y otros, titulado: Disfunción endotelial en una etapa precoz del diagnóstico de hipertensión arterial. Resulta muy interesante el tratamiento de un tema básico de gran interés en la clínica a través del uso de biomarcadores casi siempre a la disposición de nuestros profesionales de la salud en los diferentes niveles de atención como resulta ser el caso de la microalbuminuria.1 El endotelio resulta cada vez de mayor interés para investigadores y médicos de asistencia, pues es el punto de confluencia de las enfermedades vasculares, metabólicas y neurodegenerativas, y es el primer eslabón en el desarrollo de la aterosclerosis. Se conoce que los diferentes factores involucrados en la activación y daño endotelial como las altas concentraciones de ácido úrico,2 los niveles elevados de ácidos grasos,3 el envejecimiento4 y la hiperglicemia,5 son los mismos que contribuyen a posteriori con el desarrollo y las complicaciones de la placa de ateroma. Vale destacar el aporte...(AU)

Humans , Endothelium/physiopathology , Essential Hypertension/epidemiology
Int. j. cardiovasc. sci. (Impr.) ; 34(2): 124-133, Mar.-Apr. 2021. tab, graf
Article in English | LILACS | ID: biblio-1154560


Abstract Background High dietary sodium intake can induce endothelial stiffness even without changes in blood pressure. Objectives To evaluate the effects of exercise training and chronic intake of sodium chloride solution on aortic morphology of male offspring of rat dams who consumed flaxseed during lactation. Methods Female rats were fed with a control diet or a flaxseed diet during lactation. At weaning, two male offspring of each rat dam were allocated into eight groups for 180 days: four groups received a control diet e four received a flaxseed diet, with /without exercise and with/without NaCl solution supply. Aorta was collected for histomorphometric analysis. The one-way analysis of variance was used and P value < 0.05 was considered statistically significant. Results The chronic use of 1% NaCl solution led to changes in aortic histoarchitecture in the control group: increase in aortic intima-media thickness (10,4%, p<0.0001) and reduced number of elastic lamellae (-8,1%, p<0.0001). Groups of offspring of mother that consumed flaxseed during lactation, the chronic use of 1% NaCl alone did not lead to an increase in the aortic intima-media thickness. Exercise training of adult offspring increased aortic intima-media thickness (13.3%, p<0.0001), with preservation of elastic components and aortic flexibility. Conclusion Chronic salt overload caused adverse effects on the aorta of rats, and maternal consumption of the flaxseed diet during lactation protected against aortic remodeling. Int J Cardiovasc Sci. 2020; [online].ahead print, PP.0-0

Animals , Male , Female , Rats , Aorta/anatomy & histology , Seeds , Sodium Chloride, Dietary/adverse effects , Flax , Aorta/physiopathology , Physical Conditioning, Animal , Fatty Acids, Omega-3/metabolism , Rats, Wistar , Endothelium/physiopathology , Animals, Suckling
Article in English | WPRIM | ID: wpr-880338


Recent studies have revealed an inverse association between height and cardiovascular disease. However, the background mechanism of this association has not yet been clarified. Height has also been reported to be positively associated with cancer. Therefore, well-known cardiovascular risk factors, such as increased oxidative stress and chronic inflammation, are not the best explanations for this inverse association because these risk factors are also related to cancer. However, impaired blood flow is the main pathological problem in cardiovascular disease, while glowing feeding vessels (angiogenesis) are the main characteristic of cancer pathologies. Therefore, endothelial maintenance activity, especially for the productivity of hematopoietic stem cells such as CD34-positive cells, could be associated with the height of an individual because this cell contributes not only to the progression of atherosclerosis but also to the development of angiogenesis. In addition, recent studies have also revealed a close connection between bone marrow activity and endothelial maintenance; bone marrow-derived hematopoietic stem cells contribute towards endothelial maintenance. Since the absolute volume of bone marrow is positively associated with height, height could influence endothelial maintenance activity. Based on these hypotheses, we performed several studies. The aim of this review is not only to discuss the association between height and bone marrow activity, but also to describe the potential mechanism underlying endothelial maintenance. In addition, this review also aims to explain some of the reasons that implicate hypertension as a major risk factor for stroke among the Japanese population. The review also aims to clarify the anthropological reasons behind the high risk of atherosclerosis progression in Japanese individuals with acquired genetic characteristics.

Aged , Atherosclerosis/physiopathology , Body Height/physiology , Bone Marrow/physiology , Disease Progression , Endothelium/physiology , Humans , Hypertension/physiopathology , Japan/epidemiology , Male , Middle Aged , Risk Factors , Stroke/physiopathology
Frontiers of Medicine ; (4): 638-643, 2021.
Article in English | WPRIM | ID: wpr-888742


The COVID-19 pandemic has caused numerous deaths around the world. A growing body of evidence points to the important role of overwhelming inflammatory responses in the pathogenesis of COVID-19 and the effectiveness of anti-inflammation therapy against COVID-19 is emerging. In addition to affecting the lungs, COVID-19 can be a severe systemic inflammatory disease that is related to endothelial dysfunction. We are calling for closer attention to endothelial dysfunction in COVID-19 not only for fully revealing the pathogenic mechanism of COVID-19 but also for properly adjusting the strategy of clinical intervention.

COVID-19 , Endothelium , Humans , Inflammation , Pandemics , SARS-CoV-2
Article in Chinese | WPRIM | ID: wpr-879190


Child Compound Endothelium Corneum(CCEC)has the effects in invigorating the spleen and appetizing the appetite, and dissolving the accumulation of food. The recent studies have proved that it could improve gastrointestinal motility, restore physiological gastrointestinal peristalsis, increase gastrointestinal digestive motility, and enhance appetite. This trial aimed to evaluate its clinical efficacy and safety in the treatment of children's anorexia(spleen-stomach disharmony). A total of 240 children with anorexia in line with the inclusion and exclusion criteria were selected and randomly divided into experimental group and control group, with 120 in each group. Patients in the experimental group took CCEC and Erpixing Granules simulant. Patients in the control group took Erpi-xing Granules and CCEC simulant. After 21 days of treatment, there was no statistical difference in the recovery rate of anorexia, reduced food intake, eating time, weight change, traditional Chinese medicine syndrome effect, single symptom effect, and trace element Zn recovery rate between the two groups. Based on the non-inferiority test, the experimental group was not inferior to the control group in efficacy. How-ever, the effect of CCEC in reducing appetite in children with anorexia was better than that of control drugs(P<0.05). There was no statistical difference in the incidence of adverse events and adverse reactions between the two groups during the trial. This experiment confirmed the efficacy and safety of CCEC in the treatment of children's anorexia(spleen-stomach disharmony), with a safety and re-liability in clinical application. In addition, it was a better choice for children with anorexia who were mainly manifested by reduced appetite. Meanwhile, compared with granule, chewable tablets were more convenient to take in clinic. Therefore, the efficacy and safety of CCEC for the treatment of children's anorexia(spleen-stomach disharmony) were not inferior to those of Erpixing Granules, with a safety and reliability in clnic. However, due to the small sample size of this trial, the efficacy results only show a trend. It is suggested to further carry out a large-sample-size clinical study to define the clinical advantages of CCEC.

Anorexia/drug therapy , Child , Double-Blind Method , Endothelium , Humans , Reproducibility of Results , Spleen , Stomach , Treatment Outcome
Rev. Hosp. Clin. Univ. Chile ; 32(3): 201-209, 2021. tab
Article in Spanish | LILACS | ID: biblio-1353164


Endothelium is the inner layer of vessels that separates circulating blood from the rest of the body tissues. Since its discovery, it has been involved in various functions, both systemic and organ specific. Currently, endothelial damage and failure in its functions is considered a key element in pathophysiology of various clinical scenarios, among which we may find COVID-19.Hence, it has been a target in development of strategies that seek to maintain, enhance or repair its function. The purpose of the following review is to describe what an endothelial function is about, its relation with current medical practice, and its implications in the SARS- CoV-2 pandemic. (AU)

Humans , Male , Female , Endothelium/physiopathology , COVID-19/physiopathology , Coronavirus Infections/physiopathology , Endothelium/metabolism , Endothelium/virology
Braz. j. med. biol. res ; 54(6): e10423, 2021. tab, graf
Article in English | LILACS | ID: biblio-1285668


About 3000 tons of beans are not used in human food due to hardening. Several studies on bean-derived bioactive peptides have shown potential to treat some diseases, including those relying on oxidative dysfunctions. We assessed the effects of peptides extracted from hardened bean Phaseolus vulgaris (PV) on reactive oxygen species (ROS) and nitric oxide (NO) production, cytotoxic and cytoprotective effects in endothelial cells, and oxidonitrergic-dependent vasodilating effects. Extract was composed by peptide fraction <3 kDa (PV3) from hardened common bean residue. PV3 sequences were obtained and analyzed with bioinformatics. Human umbilical vein endothelial cells were treated with 10, 20, 30, and 250 µg/mL PV3. Oxidative stress was provoked by 3% H2O2. Cytotoxicity and cytoprotective effects were evaluated by MTT assay, whereas, ROS and NO were quantified using DHE and DAF-FM fluorescent probes by confocal microscopy. NO- and endothelium-dependent vasodilating effects of PV3 were assessed in isolated aortic rings. We found 35 peptides with an average mass of 1.14 kDa. There were no cell deaths with 10 and 20 μg/mL PV3. PV3 at 30 μg/mL increased cell viability, while cytotoxicity was observed only with 250 μg/mL PV3. PV3 at 10 μg/mL was able to protect cells from oxidative stress. PV3 also increased NO release without causing cell death. It also reduced relative ROS production induced by H2O2. PV3 vasodilating effects relied on endothelium-dependent NO release. PV3 obtained from low-commercial-value bean displays little cytotoxicity and exerts antioxidant effects, whereas it increases endothelial NO release.

Humans , Phaseolus , Peptides/pharmacology , Endothelium , Hydrogen Peroxide , Molecular Weight , Antioxidants/pharmacology
Braz. J. Pharm. Sci. (Online) ; 57: e19187, 2021. graf
Article in English | LILACS | ID: biblio-1350232


Propolis from stingless bees (Heterotrigona itama) is a resinous compound that exhibits antihyperglycaemia, free radical scavenging, and cardioprotective properties. The effect of propolis on diabetic vessels has not been investigated. Thus, this research aimed to determine the effect of propolis supplementation on the level of antioxidants and its mechanism of action in the aorta of diabetic rats. Male Sprague-Dawley rats were divided into five groups (n=8/group): healthy (control), untreated diabetes (DM), metformin-treated diabetes (DM+M, 300 mg/kg/day metformin), propolis-treated diabetes (DM+P, 300 mg/kg/day propolis extract) and diabetes with combined treatment (DM+M+P, dosage as former). Oral supplementation was conducted for four weeks immediately upon successful induction of diabetes by streptozotocin (60 mg/kg, intraperitoneal injection). At the end of the study, the rats were euthanised, and thoracic aorta was processed into tissue homogenates to determine the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase-1 (GPx-1) and soluble receptor for advanced glycation end-products (sRAGE). Aorta segments were harvested to examine their relaxation response towards graded concentration of acetylcholine (Ach; 10-8-10-4) M following precontraction with phenylephrine (PE; 10-6 M). Vasorelaxation towards a cumulative dose of propolis (0.01-1.00%) using PE-precontracted healthy aorta (n=6/experiments) was investigated under various simulated conditions: physiological buffer, L-NAME (10-4 M), methylene blue (10-5 M), indomethacin (10-5 M) and elevated glucose (25 mM). Propolis maintained antioxidative enzymes and sRAGE decoy molecules in the aortic tissue of the diabetic rats. The amelioration of diabetes-induced impairment of endothelium-dependent relaxation by propolis was mediated through the nitric oxide(NO)-cyclic guanosine monophosphate (cGMP) pathway. This non-clinical study reports vasoprotective property of propolis in diabetes mellitus.

Animals , Male , Rats , Propolis/analysis , Bees/anatomy & histology , Rats, Sprague-Dawley/classification , Diabetes Mellitus/drug therapy , Endothelium/abnormalities , Nitric Oxide/adverse effects , Aorta/abnormalities , Relaxation , Vasodilation , Antioxidants/pharmacology
Article in English | LILACS | ID: biblio-1355268


ABSTRACT: COVID-19 is a new disease, whose several atypical clinical manifestations began to be observed with the evolution of the pandemic, and have been investigated to understand the pathophysiology of the disease. In this article, the objective is to describe a case of angioedema in COVID-19, considered an atypical manifestation, and rarely described in the literature. The case is of a 55-year-old patient who sought medical attention for a complaint of intermittent fever for four days. On the seventh day, he manifested angioedema in the left zygomatic projection and the right subpalpebral region. The patient had no history of angioedema earlier in life. The following day, he presented a regression of the angioedema concerning the previous day. After this period, the patient progressed well and became asymptomatic. The RT-PCR laboratory test performed on the first days of manifesting symptoms was positive for SARS-CoV-2. We correlate the onset of angioedema with the possible endotheliitis present in the disease, which has been evidenced by the observation of severe endothelial injury associated with the intracellular presence of the virus in several histopathological studies of patients with COVID-19. Also, possible deregulation of the Kininogen-Kallikrein-Kinin System (KKKS) could explain this manifestation, as SARS-CoV-2 binds to the ACE2 receptor, which is responsible for degrading kinins, such as bradykinin. (AU)

RESUMO: A COVID-19 é uma doença nova, cujas diversas manifestações clínicas atípicas começaram a ser observadas com a evolução da pandemia e foram investigadas com o objetivo de compreender a fisiopatologia da doença. Neste artigo, o objetivo é descrever um caso de angioedema no COVID-19, considerado manifestação atípica e raramente descrito na literatura. O caso é de um paciente de 55 anos que procurou atendimento médico por uma queixa de febre intermitente há quatro dias. No sétimo dia, manifestou angioedema na projeção zigomática esquerda e na região subpalpebral direita. Não tinha histórico de apresentar angioedema. No dia seguinte, ele apresentou regressão do angioedema em relação ao dia anterior. Após esse período, o paciente progrediu bem e tornou-se assintomático. O teste laboratorial de RT-PCR realizado nos primeiros dias de manifestação dos sintomas foi positivo para SARS-CoV-2. Correlacionamos o início do angioedema com a possível endotelite presente na doença, o que foi evidenciado pela observação de lesão endotelial grave associada à presença intracelular do vírus em vários estudos histopatológicos de pacientes com COVID-19. Além disso, uma possível desregulação do sistema Cininogênio-Calicreína-Cinina poderia explicar essa manifestação, já que o SARS-CoV-2 se liga ao receptor ACE2, responsável pela degradação de cininas, como a bradicinina. (AU)

Humans , Male , Middle Aged , Bradykinin , Coronavirus Infections , Endothelium , Pandemics , SARS-CoV-2 , Angioedema
Acta méd. colomb ; 45(3): 1-4, jul.-set. 2020.
Article in Spanish | LILACS, COLNAL | ID: biblio-1130693


La pandemia COVID-19 sorprendió a la humanidad a través de un virus desconocido y con un comportamiento "extraño": para lo cual obviamente no estábamos preparados y que por sus características después de dos meses tornó a epidemia, y tan solo un mes después en pandemia y podrá mutar finalmente a endemia. Hasta la fecha (13 agosto) ha generado 758 761 muertos con una tasa de mortalidad promedio de 3.6 % y casos totales confirmados de 21 079 074. En Colombia hay reportados a la fecha 433 805 confirmados, 14 451 fallecidos con una mortalidad de 3.26%.Se inició como tal, aparentemente el 31 de diciembre de 2019, cuando un grupo de casos de neumonía de origen desconocido se informó en Wuhan, provincia de Hubei, China. El 9 de enero de 2020, el Centro para el Control y la Prevención de Enfermedades de China informó que el agente causante es un nuevo coronavirus 2 del síndrome respiratorio agu-do grave (SARS-CoV-2). La enfermedad causada por SARS-CoV-2 fue posteriormente denominada COVID-19 por la OMS (2, 3).

Humans , Male , Female , Endothelium , COVID-19 , Syndrome , World Health Organization , Mortality , Coronavirus Infections , Endemic Diseases
Arq. bras. cardiol ; 115(1): 52-58, jul. 2020. tab, graf
Article in Portuguese | LILACS, SES-SP | ID: biblio-1131252


Resumo Fundamento A história familiar de hipertensão (HFH) é um fator de risco consistente para diversas doenças crônicas que são acompanhadas por hipertensão. Além disso, a variabilidade da frequência cardíaca (VFC) e a vasodilatação mediada pelo fluxo (VMF), ambas relacionadas ao consumo máximo de oxigênio (VO2max), são geralmente prejudicadas durante a hipertensão. Objetivo Comparar a modulação autonômica, a função endotelial (FE) e o consumo máximo de oxigênio (VO2max) de jovens atletas, separados de acordo com a história de pressão arterial (PA) dos seus pais, a fim de investigar a influência da ascendência genética nesses parâmetros. Métodos Quarenta e seis jovens jogadores de futebol do sexo masculino (18±2 anos) foram divididos em quatro grupos: 1- pai e mãe normotensos (FM-N); 2- apenas pai hipertenso (F-H); 3- apenas mãe hipertensa (M-H); 4- pai e mãe hipertensos (FM-H). Foram realizadas medições da PA, VMF, VFC e do VO2max. Na análise estatística, foi adotado o nível de significância de 5%. Resultados O desvio padrão dos intervalos RR normais (SDNN; FM-N=314±185; FM-H=182,4± 57,8), a raiz quadrada das médias quadráticas das diferenças dos intervalos R-R sucessivos (RMSSD; FM-N=248±134; FM-H=87±51), o número de diferenças entre intervalos NN sucessivos maiores que 50 ms (NN50; FM-N=367±83,4; FM-H=229±55), a proporção de NN50 dividida pelo número total de NNs (pNN50; FM-N=32,4±6,2; FM-H=21,1±5,3) e os componentes de alta (HF; FM-N=49±8,9; FM-H=35,3±12) e baixa frequência (LF; FM-N=50,9±8,9; FM-H=64,6±12), em unidades normalizadas (%), foram significativamente mais baixos no grupo FM-H do que no grupo FM-N (p<0,05). Por outro lado, a relação LF/HF (ms2) foi significativamente maior (p<0,05). Não foram encontradas diferenças significativas no VO2max e na VMF entre os grupos (p<0,05). Conclusão Em jovens jogadores de futebol do sexo masculino, a HFH desempenha um papel potencialmente importante no comprometimento do balanço autonômico, principalmente quando ambos os pais são hipertensos, mas não apresentam alterações no VO2max e na VMF. Nesse caso, há uma diminuição no controle simpatovagal, que parece preceder o dano endotelial. (Arq Bras Cardiol. 2020; 115(1):52-58)

Abstract Background The family history of hypertension (FHH) imposes consistent risk for diverse chronic diseases that are accompanied by hypertension. Furthermore, the heart rate variability (HRV) and flow-mediated dilation (FMD) are both related to maximal oxygen uptake (VO2max), and are usually impaired during hypertension Objective To compare the autonomic modulation, the endothelial function (EF) and maximum oxygen uptake (VO2max) of young athletes, separated according to their parents' blood pressure (BP) history, in order to study the influence of their genetic background on those parameters. Methods A total of 46 young male soccer players (18±2 years of age) were divided into four groups: 1-normotensive father and mother (FM-N); 2-only father was hypertensive (F-H); 3-only mother was hypertensive (M-H); 4-father and mother were hypertensive (FM-H). Measurements of BP, FMD, HRV and VO2maxwere performed. The significance level adopted in the statistical analysis was 5%. Results The standard deviation of normal RR intervals (SDNN; FM-N=314±185; FM-H=182.4± 57.8), the square root of the mean squared differences in successive RR intervals (RMSSD; FM-N=248±134; FM-H=87±51), the number of interval differences of successive NN intervals greater than 50ms (NN50; FM-N=367±83.4; FM-H=229±55), the ratio derived by dividing NN50 by the total number of NN intervals (pNN50; FM-N=32.4±6.2; FM-H=21.1±5.3) and the high (HF; FM-N=49±8.9; FM-H=35.3±12) and low-frequency (LF; FM-N=50.9±8.9; FM-H=64.6±12) components, in normalized units (%), were significantly lower in the FM-H group than in the FM-N group (p<0.05). On the other hand, the LF/HF ratio (ms2) was significantly higher (p<0.05). We found no significant difference between the groups in VO2maxand FMD (p<0.05). Conclusions In young male soccer players, the FHH plays a potentially role in autonomic balance impairment, especially when both parents are hypertensive, but present no changes in VO2maxand FMD. In this case, there is a decrease in the sympathetic-vagal control, which seems to precede the endothelial damage (Arq Bras Cardiol. 2020; 115(1):52-58)

Humans , Male , Adolescent , Adult , Young Adult , Soccer , Endothelium/physiopathology , Hypertension/genetics , Oxygen , Oxygen Consumption , Autonomic Nervous System/parasitology , Heart Rate
Rev. Soc. Bras. Med. Trop ; 53: e20200472, 2020. tab, graf
Article in English | LILACS, ColecionaSUS, SES-SP | ID: biblio-1136838


Abstract INTRODUCTION: In the genesis of coronavirus disease (COVID-19), there is a process of endotheliitis associated with thrombotic changes, no studies have reported the use of acetylsalicylic acid (ASA) as a possible therapeutic approach. Statins could potentiate the ASA therapy. METHODS: This is a series of 14 cases with a laboratory-confirmed diagnosis of COVID-19. All patients underwent the ASA therapy. Those who had risk factors for vascular disease also underwent the high-potency statin therapy. When symptoms were totally or practically resolved, patients were discharged and advised to continue medications for a complementary time, according to the clinical evolution of each patient. RESULTS: The mean age of monitored patients was 48.6 years. A total of 78.6% patients presented with at least one comorbidity, which could have contributed as a risk factor for a poor prognosis in the evolution of COVID-19. Four patients had secondary bacterial infections; three patients needed hospitalization. None of the cases progress to stage III, and all patients had remission of symptoms, with 100% survival. CONCLUSIONS: the process of endothelial dysfunction in COVID-19 involves disseminated thrombosis, initially microvascular and later expansion into larger vessels. ASA could act as a secondary prophylaxis and prevent thrombosis from developing and reaching stage III of the disease. As this was a case series, we cannot provide definitive conclusions; however, this study allows us to formulate hypotheses and support clinical trials to evaluate benefits of the ASA therapy in the treatment of COVID-19.

Humans , Pneumonia, Viral/drug therapy , Thrombosis/drug therapy , Aspirin/therapeutic use , Coronavirus Infections/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Inflammation/drug therapy , Ischemia/drug therapy , Comorbidity , Coronavirus Infections , Endothelium/drug effects , Endothelium/pathology , Pandemics , Betacoronavirus , Middle Aged
Article in English | WPRIM | ID: wpr-787138


The purpose of this study was to characterize the genetic contribution to endothelial adaptation to exercise training. Vasoreactivity was assessed in aortas from four inbred mouse strains (129S1, B6, NON, and SJL) after 4 weeks of moderate intensity continuous exercise training (MOD), high intensity interval training (HIT) or in sedentary controls (SED). Intrinsic variations in endothelium-dependent vasorelaxation (EDR) to acetylcholine (ACh) as well as vasocontractile responses were observed across SED groups. For responses to exercise training, there was a significant interaction between mouse strain and training intensity on EDR. Exercise training had no effect on EDR in aortas from 129S1 and B6 mice. In NON, EDR was improved in aortas from MOD and HIT compared with respective SED, accompanied by diminished responses to PE in those groups. Interestingly, EDR was impaired in aorta from SJL HIT compared with SED. The transcriptional activation of endothelial genes was also influenced by the interaction between mouse strain and training intensity. The number of genes altered by HIT was greater than MOD, and there was little overlap between genes altered by HIT and MOD. HIT was associated with gene pathways for inflammatory responses. NON MOD genes showed enrichment for vessel growth pathways. These findings indicate that exercise training has non-uniform effects on endothelial function and transcriptional activation of endothelial genes depending on the interaction between genetic background and training intensity.

Acetylcholine , Animals , Aorta , Endothelium , Gene Expression Profiling , Genetic Background , Mice , Mice, Inbred Strains , Transcriptional Activation , Vasodilation
Rev. Soc. Cardiol. Estado de Säo Paulo ; 29(4,Supl): 387-392, out.-dez. 2019.
Article in Portuguese | LILACS | ID: biblio-1047320


A finalidade do sistema cardiovascular é manter uma perfusão adequada e, para tanto, conta com uma bomba eficiente (coração) e um sistema de condução apropriado, representado pelos vasos arteriais e venosos. Este artigo visa abordar os diferentes ajustes funcionais e estruturais decorrentes do treinamento físico no sistema vascular, que contribuem principalmente para melhorar a capacidade física dos indivíduos. Para tanto, o sistema conta com vários mecanismos, dentre eles neurais, hormonais e locais, que podem ser avaliados por meio de diferentes técnicas, tanto in vivo quanto in vitro. Após um período de treinamento físico, tem-se evidenciado uma melhor inter-relação entre sistema neural e local, promovendo menor atividade nervosa simpática acompanhada por simpatólise mais pronunciada. Além disso, o treinamento físico melhora a reatividade vascular de artérias, por melhorar a biodisponibilidade de óxido nítrico. Na parede vascular, o treinamento melhora o equilíbrio entre os componentes da matriz extracelular, favorecendo a redução da rigidez arterial em grandes artérias e a redução da razão parede-luz em arteríolas da musculatura locomotora e não locomotora, o que contribui para melhor distensibilidade dos vasos e redução da resistência periférica total, principalmente em casos patológicos. Por fim, o treinamento físico favorece a angiogênese na microcirculação, que contribui significativamente para nutrição tecidual

The purpose of the cardiovascular system is to maintain complete perfusion and, to this end, it has an efficient pump (the heart) and an appropriate conduction system, represented by arterial and venous vessels. This article addresses the different functional and structural adjustments resulting from physical training in the vascular system, which contribute mainly to improve the physical capacity of individuals. Therefore, the system has several mechanisms, including neural, hormonal and local mechanisms, which may be evaluated by different techniques, both in vivo and in vitro. After a period of physical training, a better interrelationship between neural and local systems has been evidenced, promoting less sympathetic nervous activity accompanied by more pronounced sympatholysis. In addition, physical training improves vascular reactivity of arteries by improving nitric oxide bioavailability. In the vascular wall, training improves balance between extracellular matrix components, favoring reduced of stiffness of the large arteries and reduced wall-to-lumen ratio in locomotor and non-locomotor muscle arterioles, which contributes to improving vessel distensibility and total peripheral resistance, especially in pathological cases. Finally, physical training favors microcirculatory angiogenesis, which contributes significantly to tissue nutrition

Exercise , Vascular Stiffness , Arteries , Cardiovascular Diseases , Cardiovascular System , Endothelium , Microcirculation , Neovascularization, Pathologic
Horiz. méd. (Impresa) ; 19(4): 84-92, Dic. 2019. tab, ilus
Article in Spanish | LILACS, LIPECS | ID: biblio-1048876


El glicocálix endotelial es una estructura sin forma definida que recubre la capa luminal del endotelio vascular y que está constituido, principalmente, por tres elementos: proteoglicanos, glucosaminoglicanos y glicoproteínas. Cumple distintas funciones, como regular la permeabilidad vascular a las moléculas y líquidos, la transducción de las fuerzas mecánicas de tensión y las cascadas de fibrinólisis y coagulación vascular; además, protege de la adhesión leucocitaria, plaquetaria y de patógenos. Los determinantes de lesión del glicocálix pueden ser de varios tipos, por ejemplo, incremento las fuerzas de tensión, especies reactivas de oxígeno (O2), aumento, a nivel plasmático, de sustancias como el sodio (hipernatremia), glucosa (hiperglicemia) y colesterol (hipercolesterolemia), y las moléculas proinflamatorias. Cualquiera de las noxas citadas, individualmente o combinadas, lesionan el glicocálix y la disfunción resultante se expresará clínicamente como disfunción endotelial, aumento de la permeabilidad vascular, paso de lipoproteínas al subendotelio, activación de la coagulación o aumento de la adhesión de plaquetas y leucocitos al endotelio.

Endothelial glycocalyx is an undefined structure covering the luminal layer of the vascular endothelium and consisting mainly of three elements: proteoglycans, glycosaminoglycans and glycoproteins. It has different functions, such as the regulation of vascular permeability to liquids and molecules; transduction of the mechanical forces of vascular tension; regulation of coagulation and fibrinolysis cascades; and protection of leukocyte, platelet and pathogen adhesion. The determinants of a glycocalyx lesion can be of several types­e.g., increased tensile forces; reactive oxygen (O2) species; increased plasma level of substances such as sodium (hypernatremia), glucose (hyperglycemia) and cholesterol (hypercholesterolemia); and pro-inflammatory molecules. Any of the above-mentioned noxas, alone or combined, injure the glycocalyx. Its dysfunction will be clinically expressed as endothelial dysfunction, increased vascular permeability, filtration of lipoproteins to the subendothelium, activation of coagulation, or increased adhesion of leukocytes and platelets to the endothelium.

Humans , Glycocalyx , Proteoglycans , Endothelium
Horiz. méd. (Impresa) ; 19(2): 28-38, Jun. 2019. tab, graf
Article in Spanish | LILACS, LIPECS | ID: biblio-1007015


Objetivo: Determinar la relación entre edad vascular (EV) y disfunción endotelial (DE) en personas adultas que viven a más de 3000 m s.n.m. Materiales y métodos: Se realizó estudio observacional, descriptivo, transversal en el Hospital Regional Docente Clínico Quirúrgico Daniel Alcides Carrión Huancayo-Perú, de enero a diciembre del 2015. Se calculó la EV mediante el SCORE de Framingham y la DE se evaluó con la prueba de vasodilatación mediada por flujo (VMF) en arteria braquial. Se consideró significativo p < 0,05. Resultados: Se incluyeron 67 personas (100 %), con edad media de 55,3 + 13,4 años (rango: 30-74), 41 (61,1 %) fueron mujeres. La EV y el valor delta fueron 57,9 + 18,3 y 2,3 + 9,3 años, respectivamente. El 53,7 % (36 participantes) presentaron EV incrementada y 22,3 % (15) fue mayor a 10 años. El aumento de edad, hipertensión arterial y sobrepeso fueron asociados con mayor riesgo cardiovascular. De 40 años a más se incrementa la EV en forma progresiva y es más frecuente en los varones. Las personas con DE presentaron riesgo alto (87,5 %) en comparación a los que tuvieron función endotelial normal (12,5 %) (p=0,007; OR: 8,52 IC95 % 1,7-41,4). Existe relación inversa entre la EV y la función endotelial (r= -0.437; p= 0.000). A mayor EV se incrementa la DE, y es mayor en los varones (Rho = -1.0; p < 0,010). Conclusiones: Existe relación inversa entre la EV y DE. La determinación de la función endotelial podría mejorar la estratificación del riesgo cardiovascular en personas que viven a gran altura y así prevenir eventos cardiovasculares.

Objective: To determine the relationship between vascular age (VA) and endothelial dysfunction (ED) in adults living at more than 3,000 m.a.s.l.Materials and methods: An observational, descriptive, cross-sectional study was performed at the Hospital Regional Docente Clínico Quirúrgico Daniel Alcides Carrión, Huancayo - Peru, from January to December 2015. The VA was calculated using the Framingham Risk Score and the ED was evaluated with the flow-mediated dilation (FMD) test in the brachial artery. A p-value <0.05 was considered significant. Results: The study included 67 individuals (100 %), whose mean age was 55.3 ± 13.4 years (range: 30-74), out of which 41 (61.1 %) were women. The VA and the delta value were 57.9 ± 18.3 and 2.3 ± 9.3 years, respectively. Fifty-three point seven percent (53.7 %) (36 participants) had an increased VA and 22.3 % (15 participants) were older than age 10. Increasing age, hypertension and overweight were associated with higher cardiovascular risk. From age 40, VA progressively increases and is more common in men. Individuals with ED presented high cardiovascular risk (87.5 %) compared to those with normal endothelial function (12.5 %) (p = 0.007; OR: 8.52; 95 % CI: 1.7-41.4). There is an inverse relationship between VA and endothelial function (r = -0.437; p = 0.000). The higher the VA , the higher the ED, which is more frequent in men (Rho = -1.0; p <0.010).Conclusions: There is an inverse relationship between VA and ED. Determining the endothelial function could improve the stratification of cardiovascular risk in individuals living at high altitude and thus prevent cardiovascular events.

Humans , Cardiovascular Diseases , Risk , Endothelium , Hypertension
Med. leg. Costa Rica ; 36(1): 84-90, ene.-mar. 2019.
Article in Spanish | LILACS | ID: biblio-1002561


Resumen La Enfermedad arterial periférica se desarrolla por la obstrucción a nivel arterial. La resultante reducción en el flujo sanguíneo puede ser asintomática o producir síntomas de insuficiencia arterial como claudicación intermitente, dolor en reposo en el grupo muscular afectado, así como la presencia de diversos grados de pérdida tisular, como úlceras, siendo éste uno de los signos más evidentes de isquemia de la extremidad. Debido a que la mayoría de los casos de Enfermedad arterial periférica tiene como etiología la ateroesclerosis resultante de la acumulación de lípidos y material fibroso entre las capas de la pared arterial en miembros inferiores, el presente artículo se centra en esta etiología como causa de la Enfermedad arterial periférica en miembros inferiores.

Abstract Peripheral artery disease is developed for an arterial obstruction. The reduction in blood flow can be asymptomatic or produce symptoms of arterial insufficiency such as intermittent claudication or rest pain in the affected muscle group, as well as the presence of different degrees of tissue loss, such as ulcers, being one of the most obvious signs of ischemia in the limb. Because the majority of cases of peripheral artery disease are caused for the atherosclerosis resulted for the accumulation of lipids and fibrous material between the layers of the artery in the lower limbs, the present article is focus on this etiology as the cause of peripheral artery disease in lower extremity.

Humans , Lower Extremity , Endothelium , Atherosclerosis , Ankle Brachial Index , Peripheral Arterial Disease/diagnosis , Intermittent Claudication