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4.
Front Nutr ; 11: 1334853, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38524849

RESUMO

Background: While salt sensitivity of blood pressure (SSBP) is a risk factor for hypertension, end-organ damage and death, most studies are conducted in western countries and in White people. We previously found that the prevalence of SSBP in Blacks living in Sub-Saharan Africa is as high as 75-80% like what has been reported in the west. Erythrocyte glycocalyx sensitivity to sodium (eGCSS), a marker of sodium-induced damage to the erythrocyte and vascular endothelial glycocalyx is thought to be related to blood pressure perturbations associated with salt intake. We hypothesized that SSBP correlates with eGCSS differently in men and women in Black people. Methods: We conducted a cross sectional study using data from our recent clinical trial from Livingstone University Teaching Hospital among 117 normotensive young adults. We used a "salt blood test" to determine eGCSS and an immediate pressor response to oral salt (IPROS) for the diagnosis of SSBP. Results: The proportion of males were equal to females and the median age (interquartile range) of the participants was 29 (22-45) years. The eGCSS scores were higher in salt-resistant females compared to salt-sensitive females and males. eGCSS correlated negatively with SSBP (AOR 0.98, 95% CI 0.97-0.99, p = 0.008), however, this relationship was driven by female sex and abrogated by male sex. Although blood pressure elevations exhibited a sustained bimodal pattern in both sexes, in males, systolic and diastolic blood pressure never returned to baseline during the time course as it did in females. Conclusion: In this study, eGCSS correlated negatively with SSBP in black women but not in black men and the pressor response to dietary salt was significantly higher in men compared to women. These results suggest that women tend to have a higher disruption of the vascular endothelial glycocalyx by an acute salt load, implying that acute changes in blood pressure may not be driven directly by the endothelial glycocalyx. Our findings suggest a novel mechanism linking eGCSS and SSBP with potential implications for sex differences in salt-induced cardiovascular disease.Clinical trial registration: https://clinicaltrials.gov/, identifier [NCT04844255].

6.
Circ Res ; 134(4): 459-473, 2024 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-38359096

RESUMO

Hypertension is the leading cause of cardiovascular disease in women, and sub-Saharan African (SSA) countries have some of the highest rates of hypertension in the world. Expanding knowledge of causes, management, and awareness of hypertension and its co-morbidities worldwide is an effective strategy to mitigate its harms, decrease morbidities and mortality, and improve individual quality of life. Hypertensive disorders of pregnancy (HDPs) are a particularly important subset of hypertension, as pregnancy is a major stress test of the cardiovascular system and can be the first instance in which cardiovascular disease is clinically apparent. In SSA, women experience a higher incidence of HDP compared with other African regions. However, the region has yet to adopt treatment and preventative strategies for HDP. This delay stems from insufficient awareness, lack of clinical screening for hypertension, and lack of prevention programs. In this brief literature review, we will address the long-term consequences of hypertension and HDP in women. We evaluate the effects of uncontrolled hypertension in SSA by including research on heart disease, stroke, kidney disease, peripheral arterial disease, and HDP. Limitations exist in the number of studies from SSA; therefore, we will use data from countries across the globe, comparing and contrasting approaches in similar and dissimilar populations. Our review highlights an urgent need to prioritize public health, clinical, and bench research to discover cost-effective preventative and treatment strategies that will improve the lives of women living with hypertension in SSA.


Assuntos
Doenças Cardiovasculares , Cardiopatias , Hipertensão Induzida pela Gravidez , Hipertensão , Gravidez , Humanos , Feminino , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/terapia , Qualidade de Vida , Hipertensão/diagnóstico , Hipertensão/epidemiologia , África Subsaariana/epidemiologia
9.
Front Pediatr ; 12: 1338672, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38379911

RESUMO

Introduction: This study was designed to measure the concentration and activity of urinary proteases that activate renal epithelial sodium channel (ENaC) mediated Na+ transport in infants with congenital heart disease, a potential mechanism for fluid retention. Methods: Urine samples from infants undergoing cardiac surgery were collected at three time points: T1) pre-operatively, T2) 6-8 h after surgery, and T3) 24 h after diuretics. Urine was collected from five heathy infant controls. The urine was tested for four proteases and whole-cell patch-clamp testing was conducted in renal collecting duct M-1 cells to test whether patient urine increased Na+ currents consistent with ENaC activation. Results: Heavy chain of plasminogen, furin, and prostasin were significantly higher in cardiac patients prior to surgery compared to controls. There was no difference in most proteases before and after surgery. Urine from cardiac patients produced a significantly greater increase in Na+ inward currents compared to healthy controls. Conclusion: Urine from infants with congenital heart disease is richer in proteases and has the potential to increase activation of ENaC in the nephron to enhance Na+ reabsorption, which may lead to fluid retention in this population.

10.
Annu Rev Pharmacol Toxicol ; 64: 159-170, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-37562495

RESUMO

Health digital twins (HDTs) are virtual representations of real individuals that can be used to simulate human physiology, disease, and drug effects. HDTs can be used to improve drug discovery and development by providing a data-driven approach to inform target selection, drug delivery, and design of clinical trials. HDTs also offer new applications into precision therapies and clinical decision making. The deployment of HDTs at scale could bring a precision approach to public health monitoring and intervention. Next steps include challenges such as addressing socioeconomic barriers and ensuring the representativeness of the technology based on the training and validation data sets. Governance and regulation of HDT technology are still in the early stages.


Assuntos
Disciplinas das Ciências Biológicas , Humanos , Sistemas de Liberação de Medicamentos , Descoberta de Drogas , Tecnologia , Atenção à Saúde
11.
Antioxidants (Basel) ; 12(10)2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37891956

RESUMO

Oxidative stress is a deteriorating condition that arises due to an imbalance between the reactive oxygen species and the antioxidant system or defense of the body. The key reasons for the development of such conditions are malfunctioning of various cell organelles, such as mitochondria, endoplasmic reticulum, and Golgi complex, as well as physical and mental disturbances. The nervous system has a relatively high utilization of oxygen, thus making it particularly vulnerable to oxidative stress, which eventually leads to neuronal atrophy and death. This advances the development of neuroinflammation and neurodegeneration-associated disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, dementia, and other memory disorders. It is imperative to treat such conditions as early as possible before they worsen and progress to irreversible damage. Oxidative damage can be negated by two mechanisms: improving the cellular defense system or providing exogenous antioxidants. Natural antioxidants can normally handle such oxidative stress, but they have limited efficacy. The valuable features of nanoparticles and/or nanomaterials, in combination with antioxidant features, offer innovative nanotheranostic tools as potential therapeutic modalities. Hence, this review aims to represent novel therapeutic approaches like utilizing nanoparticles with antioxidant properties and nanotheranostics as delivery systems for potential therapeutic applications in various neuroinflammation- and neurodegeneration-associated disease conditions.

13.
Nutrients ; 15(13)2023 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-37447199

RESUMO

The glycocalyx generally covers almost all cellular surfaces, where it participates in mediating cell-surface interactions with the extracellular matrix as well as with intracellular signaling molecules. The endothelial glycocalyx that covers the luminal surface mediates the interactions of endothelial cells with materials flowing in the circulating blood, including blood cells. Cardiovascular diseases (CVD) remain a major cause of morbidity and mortality around the world. The cardiovascular risk factors start by causing endothelial cell dysfunction associated with destruction or irregular maintenance of the glycocalyx, which may culminate into a full-blown cardiovascular disease. The endothelial glycocalyx plays a crucial role in shielding the cell from excessive exposure and absorption of excessive salt, which can potentially cause damage to the endothelial cells and underlying tissues of the blood vessels. So, in this mini review/commentary, we delineate and provide a concise summary of the various components of the glycocalyx, their interaction with salt, and subsequent involvement in the cardiovascular disease process. We also highlight the major components of the glycocalyx that could be used as disease biomarkers or as drug targets in the management of cardiovascular diseases.


Assuntos
Doenças Cardiovasculares , Doenças Vasculares , Humanos , Endotélio Vascular , Sódio , Células Endoteliais , Glicocálix , Cloreto de Sódio
14.
Circ Heart Fail ; 16(8): e010294, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37465947

RESUMO

BACKGROUND: Heart failure causes changes in Cx43 (Connexin43) regulation that are associated with arrhythmic heart disease. Pyk2 (proline-rich tyrosine kinase 2) is activated in cardiomyopathies and phosphorylates Cx43 to decrease intercellular communication. This study was designed to determine if Pyk2 inhibition improves cardiac function in a myocardial infarction (MI)-induced heart failure model in rats. METHODS: MI (ligation of left anterior descending artery) rats were treated with the Pyk2 inhibitor PF4618433. Hemodynamic and structural parameters were monitored in Sham (n=5), MI-vehicle (n=5), and MI-PF4618433 (n=8) groups. Heart tissues were collected after 6 weeks to assess Pyk2 and Cx43 protein level and localization. RESULTS: PF4618433 produced no observed adverse effects and inhibited ventricular Pyk2. PF4618433 reduced the MI infarct size from 34% to 17% (P=0.007). PF4618433 improved stroke volume (P=0.031) and cardiac output (P=0.009) in comparison to MI-vehicle with values similar to the Sham group. PF4618433 also led to an increase in the ejection fraction (P=0.002) and fractional shortening (P=0.006) when compared with the MI-vehicle (32% and 35% improvement, respectively) yet were lower in comparison with the Sham group. Pyk2 inhibition decreased Cx43 tyrosine phosphorylation (P=0.043) and maintained Cx43 at the intercalated disc in the distal ventricle 6 weeks post-MI. CONCLUSIONS: Unlike other attempts to decrease Cx43 remodeling after MI-induced heart failure, inhibition of Pyk2 activity maintained Cx43 at the intercalated disc. This may have aided in the reduced infarct size (acute time frame) and improved cardiac function (chronic time frame). Additionally, we provide evidence that Pyk2 is activated following MI in human left ventricle, implicating a novel potential target for therapy in patients with heart failure.


Assuntos
Insuficiência Cardíaca , Infarto do Miocárdio , Animais , Humanos , Ratos , Conexina 43/metabolismo , Quinase 2 de Adesão Focal/metabolismo , Insuficiência Cardíaca/etiologia , Miocárdio/metabolismo , Remodelação Ventricular/fisiologia
16.
18.
Curr Hypertens Rep ; 25(7): 107-116, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37058193

RESUMO

PURPOSE OF REVIEW: The response to natural stressors involves both cardiac stimulation and vascular changes, primarily triggered by increases in sympathetic activity. These effects lead to immediate flow redistribution that provides metabolic support to priority target organs combined with other key physiological responses and cognitive strategies, against stressor challenges. This extremely well-orchestrated response that was developed over millions of years of evolution is presently being challenged, over a short period of time. In this short review, we discuss the neurogenic background for the origin of emotional stress-induced hypertension, focusing on sympathetic pathways from related findings in humans and animals. RECENT FINDINGS: The urban environment offers a variety of psychological stressors. Real or anticipatory, emotional stressors may increase baseline sympathetic activity. From routine day-to-day traffic stress to job-related anxiety, chronic or abnormal increases in sympathetic activity caused by emotional stressors can lead to cardiovascular events, including cardiac arrhythmias, increases in blood pressure and even sudden death. Among the various alterations proposed, chronic stress could modify neuroglial circuits or compromise antioxidant systems that may alter the responsiveness of neurons to stressful stimuli. These phenomena lead to increases in sympathetic activity, hypertension and consequent cardiovascular diseases. The link between anxiety, emotional stress, and hypertension may result from an altered neuronal firing rate in central pathways controlling sympathetic activity. The participation of neuroglial and oxidative mechanisms in altered neuronal function is primarily involved in enhanced sympathetic outflow. The significance of the insular cortex-dorsomedial hypothalamic pathway in the evolution of enhanced overall sympathetic outflow is discussed.


Assuntos
Hipertensão , Angústia Psicológica , Animais , Humanos , Hipertensão/etiologia , Coração , Pressão Sanguínea/fisiologia , Hipotálamo , Sistema Nervoso Simpático
19.
Front Physiol ; 14: 1162699, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37082246

RESUMO

Volume reflex produces sympatho-inhibition that is mediated by the hypothalamic paraventricular nucleus (PVN). However, the mechanisms for the sympatho-inhibitory role of the PVN and the neurochemical factors involved remain to be identified. In this study, we proposed C-type natriuretic peptide (CNP) as a potential mediator of this sympatho-inhibition within the PVN. Microinjection of CNP (1.0 µg) into the PVN significantly decreased renal sympathetic nerve activity (RSNA) (-25.8% ± 1.8% vs. -3.6% ± 1.5%), mean arterial pressure (-15.0 ± 1.9 vs. -0.1 ± 0.9 mmHg) and heart rate (-23.6 ± 3.5 vs. -0.3 ± 0.9 beats/min) compared with microinjection of vehicle. Picoinjection of CNP significantly decreased the basal discharge of extracellular single-unit recordings in 5/6 (83%) rostral ventrolateral medulla (RVLM)-projecting PVN neurons and in 6/13 (46%) of the neurons that were not antidromically activated from the RVLM. We also observed that natriuretic peptide receptor type C (NPR-C) was present on the RVLM projecting PVN neurons detected by dual-labeling with retrograde tracer. Prior NPR-C siRNA microinjection into the PVN significantly blunted the decrease in RSNA to CNP microinjections into the PVN. Volume expansion-mediated reduction in RSNA was significantly blunted by prior administration of NPR-C siRNA into the PVN. These results suggest a potential role for CNP within the PVN in regulating RSNA, specifically under physiological conditions of alterations in fluid balance.

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