RESUMEN
Ginkgolide A (GA), a main terpenoid extracted from Ginkgo biloba, possesses biological activities such as anti-inflammatory, anti-tumor, and liver protection. However, the inhibitory effects of GA on septic cardiomyopathy remain unclear. This study aimed to explore the effects and mechanisms of GA in countering sepsis-induced cardiac dysfunction and injury. In lipopolysaccharide (LPS)-induced mouse model, GA alleviated mitochondrial injury and cardiac dysfunction. GA also significantly reduced the production of inflammatory and apoptotic cells, the release of inflammatory indicators, and the expression of oxidative stress-associated and apoptosis-associated markers, but increased the expression of pivotal antioxidant enzymes in hearts from LPS group. These results were consistent with those of in vitro experiments based on H9C2 cells. Database analysis and molecular docking suggested that FoxO1 was targeted by GA, as shown by stable hydrogen bonds formed between GA with SER-39 and ASN-29 of FoxO1. GA reversed LPS-induced downregulation of nucleus FoxO1 and upregulation of p-FoxO1 in H9C2 cells. FoxO1 knockdown abolished the protective properties of GA in vitro. KLF15, TXN2, NOTCH1, and XBP1, as the downstream genes of FoxO1, also exerted protective effects. We concluded that GA could alleviate LPS-induced septic cardiomyopathy via binding to FoxO1 to attenuate cardiomyocyte inflammation, oxidative stress, and apoptosis.
Asunto(s)
Cardiomiopatías , Lipopolisacáridos , Ratones , Animales , Lipopolisacáridos/efectos adversos , Transducción de Señal , Simulación del Acoplamiento Molecular , Miocitos Cardíacos , Cardiomiopatías/inducido químicamente , Cardiomiopatías/tratamiento farmacológico , Estrés Oxidativo , ApoptosisRESUMEN
BACKGROUND: Factors affecting heart rate variability (HRV) in patients with atrial septal defect (ASD) have not been clarified. This study sought to identify those factors and establish a preliminary risk model. METHODS: A total of 154 patients with ASD who underwent transcatheter closure and met the study requirements were analyzed in this study. Moreover, 26 patients with patent foramen ovale (PFO) were enrolled in our study as a control group. All patients underwent echocardiography and ambulatory electrocardiography before and one day after the procedure. RESULTS: The standard deviation of all normal-to-normal (NN) intervals (SDNN) and the standard deviation of the averages of the NN intervals in all 5 min segments of the entire recording (SDANN) were significantly higher and the heart rate was lower after closure than before closure in patients with ASD (SDNN: 6.08, 95% CI 3.00 to 9.15, p < 0.001; SDANN: 7.57, 95% CI 4.50 to 10.64, p < 0.001; heart rate: -1.17, 95% CI - 2.86 to - 0.48, p = 0.006). Multiple regression analyses indicated that age, sex, defect diameter, heart rate and diabetes were significantly associated with HRV indices (SDNN: R2 = 0.415; P < 0.001). SDNN and SDANN had obvious correlations with right ventricular systolic pressure (SDNN: R = - 0.370, p < 0.001; SDANN: R = - 0.360, p < 0.001). CONCLUSIONS: Factors affecting HRV in patients with ASD include age, sex, heart rate, defect size and diabetes. Furthermore, right ventricular systolic pressure plays an important role in the change in HRV.
Asunto(s)
Cateterismo Cardíaco , Electrocardiografía Ambulatoria , Frecuencia Cardíaca , Defectos del Tabique Interatrial/terapia , Adulto , Estudios de Casos y Controles , Femenino , Defectos del Tabique Interatrial/diagnóstico , Defectos del Tabique Interatrial/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Esculin, a main active ingredient from Cortex fraxini, possesses biological activities such as anti-thrombosis, anti-inflammatory, and anti-oxidation effects. However, the effects of Esculin on septic cardiomyopathy remains unclear. This study aimed to explore the protective properties and mechanisms of Esculin in countering sepsis-induced cardiac trauma and dysfunction. METHODS AND RESULTS: In lipopolysaccharide (LPS)-induced mice model, Esculin could obviously improve heart injury and function. Esculin treatment also significantly reduced the production of inflammatory and apoptotic cells, the release of inflammatory cytokines, and the expression of oxidative stress-associated and apoptosis-associated markers in hearts compared to LPS injection alone. These results were consistent with those of in vitro experiments based on neonatal rat cardiomyocytes. Database analysis and molecular docking suggested that TLR4 was targeted by Esculin, as shown by stable hydrogen bonds formed between Esculin with VAL-308, ASN-307, CYS-280, CYS-304 and ASP-281 of TLR4. Esculin reversed LPS-induced upregulation of TLR4 and phosphorylation of NF-κB p65 in cardiomyocytes. The plasmid overexpressing TLR4 abolished the protective properties of Esculin in vitro. CONCLUSION: We concluded that Esculin could alleviate LPS-induced septic cardiomyopathy via binding to TLR4 to attenuate cardiomyocyte inflammation, oxidative stress and apoptosis.
Asunto(s)
Cardiomiopatías , Lipopolisacáridos , Ratones , Ratas , Animales , Lipopolisacáridos/farmacología , Esculina/farmacología , Receptor Toll-Like 4/metabolismo , Simulación del Acoplamiento Molecular , Antiinflamatorios/farmacología , Cardiomiopatías/inducido químicamente , Cardiomiopatías/tratamiento farmacológico , FN-kappa B/metabolismoRESUMEN
Hypertension, a prevalent global cardiovascular disease, affects approximately 45.4 % of adults worldwide. Despite advances in therapy, hypertension continues to pose a significant health risk due to inadequate management. It has been established that excessive adiposity contributes majorly to hypertension, accounting for 65 to 75 % of primary cases. Fat depots can be categorised into subcutaneous and visceral adipose tissue based on anatomical and physiological characteristics. The metabolic impact and the risk of hypertension are determined more significantly by visceral fat. Perirenal adipose tissue (PRAT), a viscera enveloping the kidney, is known for its superior vascularisation and abundant innervation. Although traditionally deemed as a mechanical support tissue, recent studies have indicated its contributing potential to hypertension. Hypertensive patients tend to have increased PRAT thickness compared to those without, and there is a positive correlation between PRAT thickness and elevated systolic blood pressure. This review encapsulates the anatomical characteristics and biogenesis of PRAT. We provide an overview of the potential mechanisms where PRAT may modulate blood pressure, including physical compression, paracrine effects, and neurogenic regulation. PRAT has become a promising target for hypertension management, and continuous effort is required to further explore the underlying mechanisms.
Asunto(s)
Hipertensión , Adulto , Humanos , Tejido Adiposo/metabolismo , Obesidad/metabolismo , Adiposidad/fisiología , Riñón/metabolismoRESUMEN
As a major cause of various cardiovascular diseases, the prevalence of hypertension has been increasing in the past 30 years, leading to significant socioeconomic and health burdens. Obesity is one of the major risk factors for hypertension. Body mass index (BMI) is the most used anthropometric index to measure obesity in clinical practice and to assess the risk of obesity-related diseases. However, obesity is a heterogeneous disease, and the accumulation of fat in different body regions leads to differences in cardiovascular and metabolic risks. BMI only reflects the overall obesity but does not consider the distribution of fat and muscle mass. The limitation of BMI makes it insufficient to assess the risk of hypertension attributed to obesity. In addition, waist circumference is an easily obtainable anthropometric index to evaluate abdominal fat distribution. High waist circumference is an independent risk factor for various cardiovascular diseases and all-cause mortality regardless of BMI. Preliminary data indicate that waist circumference is significantly associated with the risk of hypertension at different BMI levels. However, routine measurement of waist circumference is currently not required in current clinical guidelines or is only recommended for obese populations, indicating an insufficient understanding of waist circumference. In this review, we summarize the measurement methods and diagnostic thresholds of waist circumference for abdominal obesity, the trend of central obesity prevalence, the superiority of waist circumference over other anthropometric indices, and recent cross-sectional and longitudinal studies on the association between obesity and hypertension.
Asunto(s)
Hipertensión , Circunferencia de la Cintura , Humanos , Hipertensión/etiología , Hipertensión/epidemiología , Hipertensión/complicaciones , Factores de Riesgo , Prevalencia , Obesidad/complicaciones , Obesidad Abdominal/complicaciones , Índice de Masa Corporal , Medición de Riesgo/métodosRESUMEN
Background: Hypertension (HTN) presents a significant global public health challenge with diverse causative factors. The accumulation of visceral adipose tissue (VAT) due to a high-fat diet (HFD) is an independent risk factor for HTN. While various studies have explored pathogenic mechanisms, a comprehensive understanding of impact of VAT on blood pressure necessitates bioinformatics analysis. Methods: Datasets GSE214618 and GSE188336 were acquired from the Gene Expression Omnibus and analyzed to identify shared differentially expressed genes between HFD-VAT and HTN-VAT. Gene Ontology enrichment and protein-protein interaction analyses were conducted, leading to the identification of hub genes. We performed molecular validation of hub genes using RT-qPCR, Western-blotting and immunofluorescence staining. Furthermore, immune infiltration analysis using CIBERSORTx was performed. Results: This study indicated that the predominant characteristic of VAT in HTN was related to energy metabolism. The red functional module was enriched in pathways associated with mitochondrial oxidative respiration and ATP metabolism processes. Spp1, Postn, and Gpnmb in VAT were identified as hub genes on the pathogenic mechanism of HTN. Proteins encoded by these hub genes were closely associated with the target organs-specifically, the resistance artery, aorta, and heart tissue. After treatment with empagliflozin, there was a tendency for Spp1, Postn, and Gpnmb to decrease in VAT. Immune infiltration analysis confirmed that inflammation and immune response may not be the main mechanisms by which visceral adiposity contributes to HTN. Conclusions: Our study pinpointed the crucial causative factor of HTN in VAT following HFD. Spp1, Postn, and Gpnmb in VAT acted as hub genes that promote elevated blood pressure and can be targets for HTN treatment. These findings contributed to therapeutic strategies and prognostic markers for HTN.
RESUMEN
Background and aims: Hypertensive disorders of pregnancy (HDP) is a significant cause of maternal and neonatal mortality. This study aims to identify risk factors for new-onset HDP and to develop a prediction model for assessing the risk of new-onset hypertension during pregnancy. Methods: We included 446 pregnant women without baseline hypertension from Liyang People's Hospital at the first inspection, and they were followed up until delivery. We collected maternal clinical parameters and biomarkers between 16th and 20th weeks of gestation. Logistic regression was used to determine the effect of the risk factors on HDP. For model development, a backward selection algorithm was applied to choose pertinent biomarkers, and predictive models were created based on multiple machine learning methods (generalised linear model, multivariate adaptive regression splines, random forest, and k-nearest neighbours). Model performance was evaluated using the area under the curve. Results: Out of the 446 participants, 153 developed new-onset HDP. The HDP group exhibited significantly higher baseline body mass index (BMI), weight change, baseline systolic/diastolic blood pressure, and platelet counts than the control group. The increase in baseline BMI, weight change, and baseline systolic and diastolic blood pressure significantly elevated the risk of HDP, with odds ratios and 95% confidence intervals of 1.10 (1.03-1.17), 1.10 (1.05-1.16), 1.04 (1.01-1.08), and 1.10 (1.05-1.14) respectively. Restricted cubic spline showed a linear dose-dependent association of baseline BMI and weight change with the risk of HDP. The random forest-based prediction model showed robust performance with the area under the curve of 0.85 in the training set. Conclusion: This study establishes a prediction model to evaluate the risk of new-onset HDP, which might facilitate the early diagnosis and management of HDP.
RESUMEN
We aim to investigate the influence of waist circumference and body mass index (BMI) on all-cause death and cardiovascular-specific death in patients with hypertension. This prospective cohort study, based on waist circumference and body mass index measurements in patients with hypertension, provided risk estimates of all-cause mortality and cardiovascular events. The waist circumference-to-BMI ratio (WtBR) is an anthropometric measure integrating waist circumference and BMI. We utilized multivariable Cox regression analysis, restricted cubic spline model, Kaplan-Meier plot, random forest analysis, and sensitivity analysis to assess the relationship of WtBR with all-cause mortality. Subsequently, Fine-Gray competing risk regression models were applied to precisely evaluate the probability of cardiovascular-specific death attributed to high WtBR. The results indicate that thea deceased group showed significantly higher WtBR and lower BMI compared with the alive groups (P < .05), while no significant difference was observed in waist circumference (P = .373). When analyzed as continuous, the risk of all-cause death elevated with increasing WtBR in the adjusted model with an HR of 2.42 (95% CI, 2.06-2.85). The restricted cubic spline illustrated an elevated risk of all-cause mortality as WtBR increased (J-shaped curve). Nevertheless, WtBR showed no significant association with cardiovascular-specific death and the prediction model exhibited a reliable performance in the testing set. This study supported that WtBR, an anthropometric measure, is independently associated with all-cause death in hypertensive patients. It's advisable to routinely assess waist circumference in hypertensive patients regardless of BMI, in order to more effectively manage the risk of obesity-related health.
Asunto(s)
Enfermedades Cardiovasculares , Hipertensión , Humanos , Índice de Masa Corporal , Hipertensión/diagnóstico , Hipertensión/epidemiología , Hipertensión/complicaciones , Circunferencia de la Cintura , Estudios Prospectivos , Obesidad/complicaciones , Obesidad/epidemiología , Factores de RiesgoRESUMEN
Background Myocardial infarction (MI) is a cardiovascular disease with high morbidity and mortality. PI16 (peptidase inhibitor 16), as a secreted protein, is highly expressed in heart diseases such as heart failure. However, the functional role of PI16 in MI is unknown. This study aimed to investigate the role of PI16 after MI and its underlying mechanisms. Methods and Results PI16 levels after MI were measured by enzyme-linked immunosorbent assay and immunofluorescence staining, which showed that PI16 was upregulated in the plasma of patients with acute MI and in the infarct zone of murine hearts. PI16 gain- and loss-of-function experiments were used to investigate the potential role of PI16 after MI. In vitro, PI16 overexpression inhibited oxygen-glucose deprivation-induced apoptosis in neonatal rat cardiomyocytes, whereas knockdown of PI16 exacerbated neonatal rat cardiomyocyte apoptosis. In vivo, left anterior descending coronary artery ligation was performed on PI16 transgenic mice, PI16 knockout mice, and their littermates. PI16 transgenic mice showed decreased cardiomyocyte apoptosis at 24 hours after MI and improved left ventricular remodeling at 28 days after MI. Conversely, PI16 knockout mice showed aggravated infract size and remodeling. Mechanistically, PI16 downregulated Wnt3a (wingless-type MMTV integration site family, member 3a)/ß-catenin pathways, and the antiapoptotic role of PI16 was reversed by recombinant Wnt3a in oxygen-glucose deprivation-induced neonatal rat cardiomyocytes. PI16 also inhibited HDAC1 (class I histone deacetylase) expression, and overexpression HDAC1 abolished the inhibition of apoptosis and Wnt signaling of PI16. Conclusions In summary, PI16 protects against cardiomyocyte apoptosis and left ventricular remodeling after MI through the HDAC1-Wnt3a-ß-catenin axis.
Asunto(s)
Infarto del Miocardio , Remodelación Ventricular , Ratones , Ratas , Animales , Remodelación Ventricular/fisiología , beta Catenina/metabolismo , Ratones Endogámicos C57BL , Miocitos Cardíacos/metabolismo , Ratones Transgénicos , Ratones Noqueados , Apoptosis/fisiología , Inhibidores de Proteasas , Modelos Animales de Enfermedad , Histona Desacetilasa 1/genéticaRESUMEN
BACKGROUND: Neutrophil counts to high-density lipoprotein cholesterol ratio (NHR), a composite marker of inflammation and lipid metabolism, has been considered as a predictor of clinical outcomes in patients with acute ischemic stroke and acute myocardial infarction. However, the predictive value of NHR for all-cause and cardiovascular mortality in the general population remains unclear. METHODS: Our study population comprised 34,335 adults in the United States obtained from the National Health and Nutrition Examination Survey (NHANES) (1999-2014) and were grouped in accordance with tertiles of NHR. Kaplan-Meier curves and log-rank test were used to investigate the differences of survival among groups. Multivariate Cox regression, restricted cubic spline analysis, and subgroup analysis were applied to explore the relationship of NHR with all-cause and cardiovascular mortality. RESULTS: The mean age of the study cohort was 49.6 ± 18.2 years and 48.4% were men. During a median follow-up of 82 months, 4,310 (12.6%) all-cause deaths and 754 (2.2%) cardiovascular deaths occurred. In a fully-adjusted Cox regression model, participants in the highest tertile had 29% higher hazard of all-cause mortality than those in the lowest tertile [hazard ratio (HR) = 1.29, 95% CI: 1.19-1.41]. For cardiovascular mortality, the continuously increased HR with 95% CIs among participants in the middle and highest tertile were 1.30 (1.06-1.59) and 1.44 (1.17-1.78), respectively. The restricted cubic spline curve indicated that NHR had a non-linear association with all-cause mortality (p for non-linearity < 0.001) and a linear association with cardiovascular mortality (p for non-linearity = 0.553). CONCLUSION: Increased NHR was a strong and independent predictor of all-cause and cardiovascular mortality in the general population.
RESUMEN
Background: The association between coronary slow flow (CSF) and coronary microvascular dysfunction (CMD) remains unclear. The objective of this study was to evaluate the correlation between the corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC) and the index of microcirculatory resistance (IMR). Methods: We consecutively enrolled patients with CSF from January 2017 to March 2018. Concurrently, we randomly selected control participants with normal flow arteries at a ratio of 3:1. Two cardiologists performed the measurements of CTFC. Coronary angiography-derived IMR (caIMR) was used to assess CMD. The caIMR was analyzed by an independent agency, with CMD being defined as caIMR >40 U. Results: A total of 111 patients with CSF and 39 patients without CSF were enrolled in this retrospective study. Compared with the non-CSF group, the CSF group had a greater proportion of males (65.8% vs. 23.1%; P<0.001) and a lower prevalence of hypertension (47.7% vs. 67.7%; P=0.042). Additionally, the CSF group had higher CTFC, coronary angiography-derived fractional flow reserve (caFFR), and caIMR regardless of left anterior descending artery (LAD), left circumflex artery (LCX), and right coronary artery (RCA) (all P values <0.001). A strong correlation between CTFC and caIMR was observed for all arteries (all P values <0.001). In the univariate analysis, male sex [hazard ratio (HR) =2.63, 95% CI: 1.30-5.31], E/e' (HR =0.88, 95% CI: 0.78-0.99), CTFC (HR =1.12, 95% CI: 1.09-1.16), and caFFR (HR =1.81, 95% CI: 1.50-2.17) were significantly correlated with CMD. After adjusting for covariates, male sex (HR =2.72, 95% CI: 1.22-6.06), CTFC (HR =1.10, 95% CI: 1.07-1.14), and caFFR (HR =1.22, 95% CI: 1.00-1.50) were independent predictors for CMD. Additionally, the best cutoff value of CTFC of all arteries for predicting CMD was 38 frames, with an area under the curve of 0.873, a sensitivity of 92.8%, and a specificity of 63.8% (P<0.001). Moreover, the best cutoff value of CTFC of LAD, LCX, and RCA to identify CMD was 35 frames, 52 frames, and 50 frames, respectively (all P values <0.001). Conclusions: CTFC correlated well with caIMR and had a strong predictive power to identify CMD.
RESUMEN
Backgrounds: The optimal blood pressure of elderly people with frailty or prefrailty is still unclear. We aimed to explore the relationship between blood pressure and mortality in the elderly with (pre)frailty. Methods: A total of 528 participants aged 60 years and older were exacted for analyses of the association between blood pressure and mortality from the database of the National Health and Nutrition Examination Survey (NHANES) (1999-2004). Kaplan-Meier curves and log-rank tests were used to investigate the differences in survival between groups. Multivariable Cox regression and restricted cubic spline (RCS) analyses were applied to explore the relationship between blood pressure and mortality. Results: During the median follow-up time of 116.5 [interquartile range (IQR) of 60-186] months, 363 all-cause deaths and 122 cardiac deaths were documented. For all-cause mortality, more participants died with systolic blood pressure (SBP) < 110 mmHg and SBP ≥ 170 mmHg (log-rank p = 0.004). After adjusting for confounders, SBP < 110 mmHg [hazard ratio (HR) 1.52, 95% CI: 0.96-2.41] and SBP ≥ 170 mmHg (HR 1.53, 95% CI: 1.09-2.15) had higher risks of all-cause mortality compared with SBP within 130-150 mmHg. There were no significant differences in all-cause mortality among DBP categories. A J-curve association was identified between the SBP and hazard ratio for all-cause mortality (p for non-linear = 0.028), with 138.6 mmHg as the lowest hazard ratio of all-cause mortality; each 10 mmHg of SBP rise was associated with a 9% increased risk in all-cause mortality (HR 1.09, 95% CI 1.00-1.18). Additionally, a non-linear relationship was determined between SBP and the hazard ratio for cardiac deaths (p for non-linear = 0.030), with 140.1 mmHg as the lowest hazard ratio of cardiac deaths. When SBP was higher than 140.1 mmHg, each 10 mmHg rise in SBP was associated with a 17% increased risk of cardiac deaths (HR 1.17, 95% CI: 1.02-1.34). Conclusion: Both lower and higher SBP levels are associated with higher risks of all-cause mortality in older individuals with (pre)frailty. There are J-shaped associations between SBP and mortality, with the optimal SBP being approximately 140 mmHg for this population specifically.