Glibenclamide reverses cardiac damage and NLRP3 inflammasome activation associated with a high refined sugar diet.

Increased energy intake from carbohydrates has been associated with major cardiovascular outcomes. Mice fed a highly-refined carbohydrate (HC) diet develop cardiac hypertrophy and inflammation. During cardiac injury, NLRP3 inflammasome is activated which results in a local inflammatory response. In this study, we hypothesized that a nom-hypoglycemic dose of glibenclamide may reverses sugar diet-induced cardiac damage by NRLP3 inflammasome inhibition. Mice were fed the HC diet for eight weeks and divided into a group treated with glibenclamide (20 mg/kg, gavage) and another with vehicle for four weeks. Afterward, hearts were excised for morphometric analysis and ex vivo function determination. NLRP3 inflammasome activation was investigated by western blotting and in situ fluorescent detection of reactive oxygen species (ROS) and active caspase-1. The HC diet promotes heart hypertrophy and collagen deposition, which were reverted by glibenclamide without ameliorating HC diet-induced insulin resistance. Changes in cardiac performance were observed in vivo by invasive catheterization and in Langendorff-perfused hearts due to the HC diet, which were prevented by glibenclamide. Hearts from HC diet mice had increased levels of NLRP3 and cleaved IL-1ß. Glibenclamide reversed ROS production and caspase-1 activity induced by HC diet. These findings suggest glibenclamide's cardioprotective effects on heart damage caused by the HC diet are related to its inhibitory action on the NLRP3 inflammasome.

Sheep naturally infected with Anaplasma ovis - evaluation of cardiac and inflammatory biomarkers

Background: Anaplasmosis, also called gall sickness or tropical bovine ehrlichiosis, is an infectious disease caused by species belonging to the genus Anaplasma in domestic and wild animals in tropical and subtropical regions. Anaplasma ovis and A. phagocytophilum are important pathogens of sheep. A. ovis is considered the most common species affecting sheep. The infection is usually subclinical and progresses with high fever, anaemia, icterus, weight loss and abortions. This study aimed to investigate changes in cardiac damage markers, oxidative stress and antioxidant status, cytokines, and acute phase proteins in sheep naturally infected with A. ovis. Materials, Methods & Results: For this purpose, a total of 40 animals, including 20 healthy sheep and 20 sheep infected with anaplasmosis, were used. A. ovis was diagnosed based on clinical findings and peripheral blood smear. Blood smears were prepared from the ear vein. The smears were stained with Giemsa and examined for the presence of Anaplasma spp. Infection was also confirmed by polymerase chain reaction (PCR) analysis. The genomic DNA was isolated from blood, and the MSP-4 gene region was amplified as A. ovis specific target gene. Twenty clinically healthy sheep of the same age group, reared under the same conditions and testing negative in the molecular assessment were used as controls. Blood samples were collected from the cephalic vein and and centrifuged to obtain serum. The serum stored at -20°C until the analysis stage. Serum samples were used for the analysis of cardiac damage markers [troponin I (cTnI), creatine kinase MB (CK-MB), lactate dehydrogenase (LDH) and aspartate transaminase (AST)], oxidative stress parameters [malondialdehyde (MDA), total antioxidant status (TAS), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)], cytokines [interleukins IL-6, IL-1ß and IL-10, tumour necrosis factor α (TNF-α), and interferon-γ (IFN-γ)] and acute phase proteins [C-reactive protein (CRP), serum amyloid A (SAA) and haptoglobin (Hp)]. cTnI and CK-MB levels were measured using a chemiluminescent immunoassay. MDA, TAS, SOD, CAT, GPx, TNF-α, IL-1ß, IL-6, IL-10, IFN-γ, SAA and Hp levels were measured by an ELISA reader. LDH, AST and CRP levels were measured in an autoanalyzer. cTnI and LDH levels were significantly increased in the infected animals compared to the healthy ones (P < 0.05). The concentration of AST was decreased in infected animals. MDA, TAS, SOD, CAT and GPx levels were significantly increased in the infected animals compared to the healthy ones (P < 0.05). The levels of the inflammatory parameters such as TNF-α, IL-1ß, IL-10 and IFN-γ were significantly increased in the infected animals compared to the healthy ones (P < 0.05). Hp level were significantly increased in the infected group compared with the control group (P < 0.05). However, there was no significant change in CK-MB, SAA and CRP concentrations in the infected animals (P > 0.05). Discussion: Ovine anaplasmosis is an obligate intracellular arthropod disease that causes widespread changes in haematobiochemical, immune response and oxidative stress parameters. Cardiac damage is often overlooked in field conditions due to the lack of adequate knowledge about the pathophysiology of the disease. Our results showed that A. ovis infection leads to significant changes in cardiac biomarkers and that the parasite can cause cardiac dysfunction. This is the first report on cardiac damage markers in Anaplasma-infected sheep. Additionally, the levels of proinflammatory and oxidative stress markers that may cause functional disorders were also found to be increased. Thus, measuring markers of cardiac function, oxidative stress and inflammation can be a useful tool in the early diagnosis of ovine anaplasmosis.

Exercise training delays cardiac remodeling in a mouse model of cancer cachexia.

AIMS: We aimed to investigate the impact of cancer cachexia and previous aerobic exercise training (AET) on cardiac function and structure in tumor bearing mice. MAIN METHODS: Colon adenocarcinoma cells 26 (CT26) were subcutaneously injected in BALB/c mice to establish robust cancer cachexia model. AET was performed on a treadmill during 45 days, 60 min/5 days per week. Cardiac function was evaluated by echocardiography and cardiac morphology was assessed by light microscopy. The protein expression levels of mitochondrial complex were analyzed by Western blotting. The mRNA levels of genes related to cardiac remodeling and autophagy were analyzed by quantitative Real-Time PCR. KEY FINDINGS: Our data confirms CT26 tumor bearing mice as a well-characterized and robust model of cancer cachexia. CT26 mice exhibited cardiac remodeling and dysfunction characterized by cardiac atrophy and impaired left ventricle ejection fraction paralleled by cardiac necrosis, inflammation and fibrosis. AET partially reversed the left ventricle ejection fraction and led to significant anti-cardiac remodeling effect associated reduced necrosis, inflammation and cardiac collagen deposition in CT26 mice. Reduced TGF-ß1 mRNA levels, increased mitochondrial complex IV protein levels and partial recovery of BNIP3 mRNA levels in cardiac tissue were associated with the cardiac effects of AET in CT26 mice. Thus, we suggest AET as a powerful regulator of key pathways involved in cardiac tissue homeostasis in cancer cachexia. SIGNIFICANCE: Our study provides a robust model of cancer cachexia, as well as highlights the potential and integrative effects of AET as a preventive strategy for reducing cardiac damage in cancer cachexia.

Efecto del Medio Condicionado de la Línea Celular H9C2 Tratada con Dehidroepiandrosterona y Expuesta a Daño sobre la Motilidad de Células Troncales Mesenquimales / Effect of the Conditioned Medium from H9C2 Cell Line Treated with Dehydroepiandrosterone and Exposed to Damage on the Motility of Mesenchymal Stem Cells

RESUMEN: Las enfermedades cardiovasculares (ECV) son la principal causa de muerte a nivel mundial, donde la terapia con Células Troncales Mesenquimales (CTM) representa una alternativa para los pacientes que no logran recuperarse con los tratamientos actuales. El lograr que las CTM residentes se movilicen al órgano afectado representaría una ventaja para el manejo terapéutico de las ECV. La dehidroepiandrosterona (DHEA) es un precursor hormonal cuyos niveles disminuyen a lo largo de la vida, lo que se ha asociado al desarrollo de ECV. Diversos estudios han demostrado que el consumo de DHEA previene y mejora la condición cardiaca, aunque no se sabe si esto ocurre porque se ejerce un efecto en los cardiomiocitos y estos, a su vez, hacia las CTM. El objetivo del presente estudio fue determinar el efecto del medio condicionado procedente de la línea H9C2 pretratada con DHEA y sometida a daño, sobre la motilidad de CTM, llevando a cabo un ensayo de cierre de herida. El pretratamiento con DHEA y el daño en la línea H9C2, promueve la motilidad de CTM. El estímulo de la motilidad de CTM por un efecto indirecto de DHEA podría ser una estrategia terapéutica para el daño cardiaco.

ABSTRACT: Cardiovascular diseases (CVD) are the leading cause of death worldwide. Mesenchymal Stem Cell (MSC) therapy is an alternative for patients who cannot recover with current treatments. Ensure movilization of MSC to the affected organs would represent an advantage for therapeutic management of CVD. Dehydroepiandrosterone (DHEA) is a hormone precursor whose levels decrease throughout life, which has been associated with the onset of CVD. Several studies have shown that DHEA consumption, prevents and improves heart condition, although it is not known if this is because an effect on cardiomyocytes is exercised on these cells and this, in turn, to CTM. The aim of this study was to determine the effect of conditioned medium from H9C2 cell line pretreated with DHEA and subjected to damage, on the motility of CTM, performing a wound healing assay. Pretreatment with DHEA and damage to H9C2 cell line, promotes motility of CTM. Stimulation of CTM motility by an indirect effect of DHEA could be a therapeutic strategy for heart damage.

Crosstalk between obesity and MMP-9 in cardiac remodelling -a cross-sectional study in apparent treatment-resistant hypertension.

The balance between matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) plays a key role in the development of hypertension and obesity. We aimed to evaluate the levels of MMP-2 and 9 and TIMP-2 and -1 in obese and non-obese apparent treatment-resistant hypertensive subjects (aTRH) and its association with cardiac hypertrophy. This cross-sectional study enrolled 122 subjects and divided into obese aTRH (n = 67) and non-obese (n = 55) group. Clinical and biochemical data were compared between both groups, including office BP, ambulatory BP, plasma MMP-2 and 9, TIMP-2 and 1 and left ventricular mass index (LVMI). We found higher MMP-9 levels and MMP-9/TIMP-1 ratio in obese aTRH subjects but no difference in MMP-2 and TIMP-1 levels. Obesity influenced MMP-9 levels [ß = 20.8 SE =8.6, p = 0.02) independently of potential confounders. In addition, we found a positive correlation between MMP-9 and anthropomorphic parameters. Finally, obese aTRH subjects with left ventricular hypertrophy (LVH) had greater MMP-9 levels compared with non-obese with LVH. Our study suggests that MMP-9 levels are influenced by obesity and may directly participate in the progressive LV remodelling process, suggesting a possible role for a higher cardiovascular risk in apparent resistant hypertensive subjects.

Baroreflex deficit are associated with target organ damage / Os déficits de barorreflexo estão associados ao dano do órgão alvo

As is well known, there are different pathophysiological conditions in which baroreflex deficit is enrolled in end-organ damage like hypertension, heart failure and myocardial infarction. The purpose of this study was to investigate the mechanisms enrolled in those relationships using a baroreflex deficit­induced model. Sinoaortic-denervated (SAD) rats were used as a model of arterial baroreflex impairment. Male Wistar rats were divided into: control (n = 9), and SAD (n = 8, 30 days) groups. SAD was performed using the method previously described by Krieger (1964). Cardiac morphology was assessed by echocardiography BP, HR and BP, and pulse interval (PI) variabilities were analyzed using a data acquisition system (Codas, 2kHz). Stroke volume and peripheral and regional resistance were evaluated using colored microspheres. SAD induced LV hypertrophy estimated by LV/BW mass using echocardiography. BP (C: 106±0.6 vs. SAD: 108±2 mmHg) and HR (C: 355±7 vs. SAD: 357±15 bpm) were not modified by SAD, while BP variability (C: 6.2±0.84 vs SAD: 14±0.9 mmHg) and PI variability (C: 24±0.7 vs SAD:17±0.8 ms) were increased and decreased, respectively. Moreover, a reduction was observed in stroke volume (C: 0.31±0.02 vs SAD: 0.25±0.01 mL/ min) and an increase in total peripheral resistance (C: 0.97±0.07 vs. SAD: 1.23±0.07 mL/min/mmHg) in SAD animals. Those alterations resulted in increased cardiac vascular resistance (C: 35±1.6 vs. SAD:66±2.3 mmHg/mL/min/g) and renal vascular resistance (C: 31±1.2 vs. SAD: 75±2.2 mmHg/mL/min/g) in the SAD group. SAD induced an augment in cardiac and renal damage as cardiac morphology by histological techniques showed increased arterial wall and interstitial fibroses, and renal morphology showed interstitial fibroses and a decreased Bowmann space. Conclusion: Total baroreflex dysfunction impaired BP and HR variabilities associated with decreased stroke volume and increased peripheral and regional resistance. These adjustments may play an important role in target organ damage in different pathological conditions; even BP values were maintained at the control levels

Existem diferentes condições fisiopatológicas em que o déficit de barorreflexo está associado ao dano do órgão final, como hipertensão, insuficiência cardíaca e infarto do miocárdio. O objetivo deste estudo foi investigar os mecanismos inscritos nestes relacionamentos usando um modelo induzido por déficit de barorreflexo. Foram utilizados ratos com desnervação sino-aórtica (SAD) como modelo de comprometimento barorreflexo arterial. Os ratos Wistar machos foram divididos em grupos controle (n = 9) e SAD (n = 8, 30 dias). O SAD foi realizado utilizando o método anteriormente descrito por Krieger (1964). A morfologia cardíaca foi avaliada pela ecocardiografia PA, e as variabilidades de FC e PA, e do intervalo de pulso (IP) foram analisadas usando um sistema de aquisição de dados (Codas, 2kHz). O volume sistólico e a resistência periférica e regional foram avaliados utilizando microesferas coloridas. SAD induziu hipertrofia do VE estimada pela massa de VE/PC usando ecocardiografia. PA (C: 106±0,6 vs. SAD: 108±2 mmHg) e FC (C: 355±7 vs. SAD: 357±15 bpm) não foram modificados pelo SAD, enquanto a variabilidade da PA (C: 6,2±0,84 vs. SAD: 14±0,9 mmHg) e a variabilidade de PI (C: 24±0,7 vs. SAD: 17±0,8 ms) aumentaram e diminuíram, respectivamente. Além disso, observou-se uma redução no volume sistólico (C: 0,31± 0,02 vs SAD: 0,25 ± 0,01 mL/min) e um aumento na resistência periférica total (C: 0,97±0,07 vs. SAD: 1,23±0,07 mL/min/mmHg) em animais SAD. Essas alterações resultaram em aumento da resistência vascular cardíaca (C: 35±1,6 vs. SAD: 66 ± 2,3 mmHg/mL/min/g) e resistência vascular renal (C: 31±1,2 vs. SAD: 75±2,2 mmHg/mL/min/g) no grupo SAD. SAD induziu um aumento no dano cardíaco e renal como a morfologia cardíaca por técnicas histológicas mostrou aumento da parede arterial e fibrose intersticial, e a morfologia renal mostrou fibrose intersticial e uma diminuição do espaço de Bowmann. A disfunção barorreflexa total prejudicou as variabilidades de PA e FC associadas à diminuição do volume sistólico e ao aumento da resistência periférica e regional. Esses ajustes podem desempenhar um papel importante no dano de órgãos alvo em diferentes condições patológicas; até mesmo os valores da PA foram mantidos nos níveis de controle

Marcadores cardíacos na medicina veterinária / Cardiac markers in veterinary medicine

Os marcadores cardíacos são utilizados com o intuito de auxiliar no diagnóstico clínico de animais com doença cardíaca com maior acurácia e em menor tempo possível, possibilitando o estabelecimento do prognóstico e a terapia precocemente. Entretanto, em medicina veterinária, no Brasil, sua aplicabilidade ainda é, em geral, restrita a pesquisas. Esta revisão tem como objetivo abordar os principais marcadores cardíacos para que futuramente estes possam se tornar índices essenciais na avaliação cardíaca.

Cardiac markers have been used in order to assist clinical diagnosis of animals with heart disease, more accurately, enabling the establishment of earlier prognosis and therapy. However, in Brazilian veterinary medicine, these markers are generally still restricted to researches. This review aims to approach the major cardiac markers, which further may become essential indexes in heart assessment.

Marcadores cardíacos na medicina veterinária

Cardiac markers have been used in order to assist clinical diagnosis of animals with heart disease, more accurately, enabling the establishment of earlier prognosis and therapy. However, in Brazilian veterinary medicine, these markers are generally still restricted to researches. This review aims to approach the major cardiac markers, which further may become essential indexes in heart assessment.

Os marcadores cardíacos são utilizados com o intuito de auxiliar no diagnóstico clínico de animais com doença cardíaca com maior acurácia e em menor tempo possível, possibilitando o estabelecimento do prognóstico e a terapia precocemente. Entretanto, em medicina veterinária, no Brasil, sua aplicabilidade ainda é, em geral, restrita a pesquisas. Esta revisão tem como objetivo abordar os principais marcadores cardíacos para que futuramente estes possam se tornar índices essenciais na avaliação cardíaca.

Marcadores cardíacos na medicina veterinária

Cardiac markers have been used in order to assist clinical diagnosis of animals with heart disease, more accurately, enabling the establishment of earlier prognosis and therapy. However, in Brazilian veterinary medicine, these markers are generally still restricted to researches. This review aims to approach the major cardiac markers, which further may become essential indexes in heart assessment.

Os marcadores cardíacos são utilizados com o intuito de auxiliar no diagnóstico clínico de animais com doença cardíaca com maior acurácia e em menor tempo possível, possibilitando o estabelecimento do prognóstico e a terapia precocemente. Entretanto, em medicina veterinária, no Brasil, sua aplicabilidade ainda é, em geral, restrita a pesquisas. Esta revisão tem como objetivo abordar os principais marcadores cardíacos para que futuramente estes possam se tornar índices essenciais na avaliação cardíaca.

Marcadores cardíacos na medicina veterinária

Cardiac markers have been used in order to assist clinical diagnosis of animals with heart disease, more accurately, enabling the establishment of earlier prognosis and therapy. However, in Brazilian veterinary medicine, these markers are generally still restricted to researches. This review aims to approach the major cardiac markers, which further may become essential indexes in heart assessment.

Os marcadores cardíacos são utilizados com o intuito de auxiliar no diagnóstico clínico de animais com doença cardíaca com maior acurácia e em menor tempo possível, possibilitando o estabelecimento do prognóstico e a terapia precocemente. Entretanto, em medicina veterinária, no Brasil, sua aplicabilidade ainda é, em geral, restrita a pesquisas. Esta revisão tem como objetivo abordar os principais marcadores cardíacos para que futuramente estes possam se tornar índices essenciais na avaliação cardíaca.