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1.
Adv Exp Med Biol ; 1216: 65-77, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31894548

RESUMEN

The aim of this chapter is to review the results of recent studies analyzing the role of oxidative stress and systemic inflammation as potential contributors to frailty and CVD, and to explain a possible pathogenic relationship between the latter two conditions. Available evidence suggests that frail patients have elevated levels of oxidative stress biomarkers and proinflammatory cytokines, as well as with reduced concentrations of endogenous antioxidants. This implies that oxidative stress and systemic inflammation might play a role in the pathogenesis of frailty, but an underlying mechanism of this relationship is still mostly hypothetical. Oxidative stress and systemic inflammation are also involved in the pathogenesis of CVD. Cardiovascular conditions are established risk factor for frailty and in turn, presence of frailty constitutes an unfavorable prognostic factor in cardiac patients. Finally, some cardiovascular risk factors, such as lack of physical activity, smoking, obesity and inappropriate diet, are also involved in the etiology of oxidative stress, chronic inflammation and frailty. This complex interplay between intrinsic and extrinsic elements should be considered during holistic management of older persons with frailty and/or cardiovascular conditions.


Asunto(s)
Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/metabolismo , Anciano Frágil , Fragilidad/complicaciones , Fragilidad/metabolismo , Inflamación/complicaciones , Inflamación/metabolismo , Estrés Oxidativo , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/patología , Fragilidad/patología , Humanos , Inflamación/patología
2.
Adv Clin Chem ; 94: 261-321, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31952573

RESUMEN

Studies have linked obesity, metabolic syndrome, type 2 diabetes, cardiovascular disease (CVD), nonalcoholic fatty liver disease (NAFLD) and dementia. Their relationship to the incidence and progression of these disease states suggests an interconnected pathogenesis involving chronic low-grade inflammation and oxidative stress. Metabolic syndrome represents comorbidities of central obesity, insulin resistance, dyslipidemia, hypertension and hyperglycemia associated with increased risk of type 2 diabetes, NAFLD, atherosclerotic CVD and neurodegenerative disease. As the socioeconomic burden for these diseases has grown signficantly with an increasing elderly population, new and alternative pharmacologic solutions for these cardiometabolic diseases are required. Adipose tissue, skeletal muscle and liver are central endocrine organs that regulate inflammation, energy and metabolic homeostasis, and the neuroendocrine axis through synthesis and secretion of adipokines, myokines, and hepatokines, respectively. These organokines affect each other and communicate through various endocrine, paracrine and autocrine pathways. The ultimate goal of this review is to provide a comprehensive understanding of organ crosstalk. This will include the roles of novel organokines in normal physiologic regulation and their pathophysiological effect in obesity, metabolic syndrome, type 2 diabetes, CVD, NAFLD and neurodegenerative disorders.


Asunto(s)
Adipoquinas/metabolismo , Enfermedades Cardiovasculares/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Síndrome Metabólico/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Obesidad/metabolismo , Humanos
3.
J Sci Food Agric ; 100(2): 846-854, 2020 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-31646650

RESUMEN

BACKGROUND: Pomegranate has antioxidant, cardioprotective and anti-inflammatory properties. We designed a crossover study aimed at determining if consumption of pomegranate juice (PJ) improves lipid profile and oxidative and inflammatory biomarkers of hemodialysis patients. Forty-one hemodialysis patients were randomly assigned to one of two groups: PJ-treated group receiving 100 mL of natural PJ immediately after their dialysis session three times a week and the control group receiving the usual care. After 8 weeks, a 4-week washout period was established and then the role of the groups was exchanged. Lipid profile, blood pressure and oxidative and inflammatory biomarkers were measured before and after each sequence. RESULTS: Based on the results of intention-to-treat analysis, triglycerides were decreased in PJ condition and increased in the controls. Conversely, high-density lipoprotein cholesterol was increased in PJ and decreased in the control group. Total and low-density lipoprotein cholesterol did not significantly change in either condition. Systolic and diastolic blood pressure significantly decreased in PJ condition. Total antioxidant capacity increased in PJ condition (P < 0.001) and decreased in the controls (P < 0.001). Conversely, malondialdehyde and interleukin-6 decreased in PJ (P < 0.001) and increased in the control group (P ≤ 0.001). The changes of these biomarkers were significantly different between the two conditions. CONCLUSIONS: Eight-week PJ consumption showed beneficial effects on blood pressure, serum triglycerides, high-density lipoprotein cholesterol, oxidative stress and inflammation in hemodialysis patients. © 2019 Society of Chemical Industry.


Asunto(s)
Enfermedades Cardiovasculares/metabolismo , Jugos de Frutas y Vegetales/análisis , Insuficiencia Renal Crónica/dietoterapia , Adulto , Anciano , Presión Sanguínea , Enfermedades Cardiovasculares/inmunología , Enfermedades Cardiovasculares/fisiopatología , Enfermedades Cardiovasculares/prevención & control , Estudios Cruzados , Femenino , Humanos , Masculino , Malondialdehído/metabolismo , Persona de Mediana Edad , Estrés Oxidativo , Diálisis Renal , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/terapia , Triglicéridos/metabolismo
5.
Ann Agric Environ Med ; 26(4): 512-522, 2019 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-31885222

RESUMEN

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a common metabolic disorder, which carries a risk for atherosclerosis and cardiovascular impairment. The purpose of this review is to demonstrate the role of acetylsalicylic acid (ASA) in primary cardiovascular prevention in T2DM patients, as well as present an outline of microRNAs (miRNA) relevant to ASA therapy and should be evaluated as targets to improve treatment. BRIEF DESCRIPTION OF STATE OF KNOWLEDGE: Although the etiology of hypercoagulable state in T2DM is considered multifactorial, attention mainly focuses on platelet disturbances. Platelets in T2DM not only demonstrate intensified adhesion, activation, aggregation, and thrombin generation, but are likely to deliver miRNAs at specific sites of action in the cardiovascular system, hence contributing to the pathogenesis of cardiovascular events. OBJECTIVE: Since cardiovascular disease (CVD) is currently the leading cause of mortality among T2DM patients, appropriate risk stratification and management is necessary to reduce morbidity and mortality in this group. A large number of T2DM patients show inadequate response to antiplatelet therapy, which currently revolves around ASA, despite compliance with treatment regimens proposed by the guidelines. CONCLUSIONS: The review shows that the use of ASA for primary prevention is beneficial in patients at high cardiovascular risk. However, it is important to select patients in whom ASA therapy will bring the most beneficial outcome with minimal risk for adverse effects. This can be potentially achieved with the use of unique biomarkers. The biologically diverse characteristics of miRNA make them a promising novel biomarker and potential tool for better risk stratification, as well as antiplatelet therapy optimization.


Asunto(s)
Aspirina/administración & dosificación , Enfermedades Cardiovasculares/prevención & control , MicroARN Circulante/genética , Diabetes Mellitus Tipo 2/complicaciones , Animales , Plaquetas/citología , Plaquetas/efectos de los fármacos , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/metabolismo , MicroARN Circulante/metabolismo , Diabetes Mellitus Tipo 2/sangre , Humanos , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Prevención Primaria
6.
Anal Bioanal Chem ; 411(29): 7725-7735, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31760445

RESUMEN

The rapid and simultaneous detection of DNA and protein biomarkers is necessary to detect the outbreak of a disease or to monitor a disease. For example, cardiovascular diseases are a major cause of adult mortality worldwide. We have developed a rapidly adaptable platform to assess biomarkers using a microfluidic technology. Our model mimics autoantibodies against three proteins, C-reactive protein (CRP), brain natriuretic peptide (BNP), and low-density lipoprotein (LDL). Cell-free mitochondrial DNA (cfmDNA) and DNA controls are detected via fluorescence probes. The biomarkers are covalently bound on the surface of size- (11-15 µm) and dual-color encoded microbeads and immobilized as planar layer in a microfluidic chip flow cell. Binding events of target molecules were analyzed by fluorescence measurements with a fully automatized fluorescence microscope (end-point and real-time) developed in house. The model system was optimized for buffers and immobilization strategies of the microbeads to enable the simultaneous detection of protein and DNA biomarkers. All prime target molecules (anti-CRP, anti-BNP, anti-LDL, cfmDNA) and the controls were successfully detected both in independent reactions and simultaneously. In addition, the biomarkers could also be detected in spiked human serum in a similar way as in the optimized buffer system. The detection limit specified by the manufacturer is reduced by at least a factor of five for each biomarker as a result of the antibody detection and kinetic experiments indicate that nearly 50 % of the fluorescence intensity is achieved within 7 min. For rapid data inspection, we have developed the open source software digilogger, which can be applied for data evaluation and visualization. Graphical abstract.


Asunto(s)
Enfermedades Cardiovasculares/metabolismo , Ácidos Nucleicos Libres de Células/análisis , Dispositivos Laboratorio en un Chip , Proteínas/análisis , Autoanticuerpos/análisis , Biomarcadores/análisis , Colorantes Fluorescentes/química , Humanos , Límite de Detección , Microesferas , Proteínas/inmunología
7.
Methodist Debakey Cardiovasc J ; 15(3): 200-206, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31687099

RESUMEN

Nitric oxide (NO) is continually produced by the enzyme nitric oxide synthase (NOS) and is essential to the control and effectiveness of the cardiovascular system. However, there is a substantial reduction in NOS activity with aging that can lead to the development of hypertension and other cardiovascular complications. Fortunately, NO can also be produced by the sequential reduction of inorganic nitrate to nitrite and then to NO. Nitric oxide from inorganic nitrate supplementation has been found to have the same cardioprotective benefits of NO produced by NOS. Moreover, it can effectively compensate for declining NOS activity due to aging or NOS inhibition by oxidative stress, hypoxia, or other factors. This review covers some of the major cardiovascular regulatory actions of NO and presents evidence that NO from inorganic nitrate supplementation can provide (1) compensation when NOS activity is inadequate, and (2) cardioprotective benefits beyond that provided by a healthy NOS system. In addition, it discusses how to obtain a safe and efficacious range of inorganic nitrate.


Asunto(s)
Enfermedades Cardiovasculares/prevención & control , Sistema Cardiovascular/efectos de los fármacos , Suplementos Dietéticos , Nitratos/uso terapéutico , Óxido Nítrico/metabolismo , Animales , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/fisiopatología , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/fisiopatología , Suplementos Dietéticos/efectos adversos , Estado de Salud , Humanos , Nitratos/efectos adversos , Óxido Nítrico Sintasa/metabolismo , Factores de Riesgo , Resultado del Tratamiento
9.
Nat Med ; 25(11): 1667-1679, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31700182

RESUMEN

Increases in the prevalence of noncommunicable diseases (NCDs), particularly cardiometabolic diseases such as cardiovascular disease, stroke and diabetes, and their major risk factors have not been uniform across settings: for example, cardiovascular disease mortality has declined over recent decades in high-income countries but increased in low- and middle-income countries (LMICs). The factors contributing to this rise are varied and are influenced by environmental, social, political and commercial determinants of health, among other factors. This Review focuses on understanding the rise of cardiometabolic diseases in LMICs, with particular emphasis on obesity and its drivers, together with broader environmental and macro determinants of health, as well as LMIC-based responses to counteract cardiometabolic diseases.


Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Diabetes Mellitus/epidemiología , Enfermedades Metabólicas/epidemiología , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/patología , Países en Desarrollo , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patología , Política de Salud , Humanos , Enfermedades Metabólicas/metabolismo , Enfermedades Metabólicas/patología , Factores de Riesgo
10.
Nat Med ; 25(11): 1657-1666, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31700185

RESUMEN

The prevalence of cardiometabolic disorders in both women and men has increased worldwide and is linked to a rise in obesity and obesity-associated associated clustering of other cardiometabolic risk factors such as hypertension, impaired glucose regulation and dyslipidemia. However, the predominance of common types of cardiometabolic disorders such as heart failure, atrial fibrillation and ischemic heart disease is sex specific, and our identification of these and the underlying mechanisms is only just emerging. New evidence suggests that sex hormones, sex-specific molecular mechanisms and gender influence glucose and lipid metabolisms, as well as cardiac energy metabolism, and function. Here we review sex differences in cardiometabolic risk factors, associated preclinical and clinical cardiac disorders and potential therapeutic avenues.


Asunto(s)
Enfermedades Cardiovasculares/metabolismo , Síndrome Metabólico/metabolismo , Obesidad/metabolismo , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/patología , Metabolismo Energético , Femenino , Glucosa/metabolismo , Humanos , Hipertensión/complicaciones , Hipertensión/metabolismo , Hipertensión/patología , Metabolismo de los Lípidos/genética , Masculino , Síndrome Metabólico/patología , Obesidad/patología , Factores de Riesgo , Caracteres Sexuales
11.
Vasc Health Risk Manag ; 15: 309-316, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31692533

RESUMEN

Experimentally induced injury triggers up-regulation and mobilization of stem cells in Apoe -/- mice that causes accelerated atherosclerosis. Abca1 -/- Abcg1-/- mice have chronic activation of stem cell up-regulation/mobilization and accelerated atherosclerosis. In addition, the Abca1 -/- Abcg1-/- mice have elevation of serum cytokines G-CSF, IL-17 and IL-23, each necessary for stem cell mobilization. IL-17 and IL-23 are elevated in two human illnesses that have cardiovascular (CV) risk independent of traditional risk factors-SLE and psoriasis. Serum G-CSF, which can be elevated in liver disease, predicts major adverse cardiovascular events in humans. These serum cytokine elevations suggest activation of the stem cell mobilization mechanism in humans that results, as in mice, in accelerated atherosclerosis. Efforts to reduce CV disease in these patient populations should include mitigation of the diseases that trigger stem cell mobilization. Since activation of the stem cell up-regulation/mobilization mechanism appears to accelerate human atherosclerosis, use of stem cells as therapy for arterial occlusive disease should distinguish between direct administration of stem cells and activation of the stem cell up-regulation/mobilization mechanism.


Asunto(s)
Enfermedades Cardiovasculares/patología , Movimiento Celular , Hepatopatías/patología , Psoriasis/patología , Células Madre/patología , Transportador 1 de Casete de Unión a ATP/deficiencia , Transportador 1 de Casete de Unión a ATP/genética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 1/deficiencia , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 1/genética , Animales , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/prevención & control , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Humanos , Mediadores de Inflamación/metabolismo , Hepatopatías/genética , Hepatopatías/metabolismo , Hepatopatías/terapia , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/metabolismo , Lupus Eritematoso Sistémico/patología , Lupus Eritematoso Sistémico/terapia , Ratones Noqueados para ApoE , Fenotipo , Pronóstico , Psoriasis/genética , Psoriasis/metabolismo , Psoriasis/terapia , Factores de Riesgo , Células Madre/metabolismo
12.
Rev Cardiovasc Med ; 20(3): 153-160, 2019 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-31601089

RESUMEN

Exosomes, nanosized lipid bilayer membranous vesicles, are secreted by a variety of cells and contain protein, lipids, mRNA, miRNA, and signaling molecules that participate in intercellular material transfer and information exchange through binding, fusion or endocytosis. Exosomes mediate the gene expression of target cells and regulate pathological and physiological processes, thereby playing a key role in the occurrence and development of various diseases. Accumulated studies has shown that exosomes hold therapeutic potential though their anti-apoptotic and anti-fibrotic roles. They also have been shown to promote angiogenesis, inhibit ventricular remodeling and improve cardiac function, as well as inhibiting local inflammation and regulating the immune response. As such, exosomes represent a new target for the treatment of cardiovascular diseases. This review summarizes the literature in this field to date, including the basic biological characteristics of exosomes, and new progress in the understanding of the mechanisms of their involvement in immune regulation in cardiovascular diseases. In this way, it servrs as a basis for future research and the development of therapeutic exosomes.


Asunto(s)
Enfermedades Cardiovasculares/inmunología , Sistema Cardiovascular/inmunología , Exosomas/inmunología , Sistema Inmunológico/inmunología , Animales , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/fisiopatología , Enfermedades Cardiovasculares/terapia , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/fisiopatología , Exosomas/metabolismo , Exosomas/trasplante , Humanos , Sistema Inmunológico/metabolismo , Sistema Inmunológico/fisiopatología , Pronóstico , Transducción de Señal
13.
J Agric Food Chem ; 67(44): 12191-12198, 2019 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-31588747

RESUMEN

Fermented black garlic has multiple beneficial biological activities, including cardiovascular protection, anticancer, hepatoprotective, and antibacterial properties. In this study, metabolic differences in the properties of black and fresh garlic were investigated via liquid chromatography quadrupole/time-of-flight-based metabolomics, leading to the identification of characteristic components. Fermented black garlic samples and their Amadori products (AC) promoted angiogenesis, prevented thrombus formation by rescuing chemical-induced vascular lesions in zebrafish, and inhibited H2O2-induced injury of endothelial cells, thus reducing the risk of cardiovascular disease. AC suppressed activation of the mitogen-activated protein kinase pathway through inhibition of p38 and ERK1/2 phosphorylation, in turn, increasing the availability of c-Fos/c-Jun or c-Jun/c-Jun complexes for apoptotic resistance. Clarification of the associated signaling pathways should therefore provide a solid foundation for optimization of black garlic-based therapies.


Asunto(s)
Enfermedades Cardiovasculares/prevención & control , Ajo/química , Extractos Vegetales/administración & dosificación , Animales , Biomarcadores/análisis , Biomarcadores/metabolismo , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/metabolismo , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Femenino , Humanos , Peróxido de Hidrógeno/toxicidad , Masculino , Espectrometría de Masas , Metabolómica , Proteínas Quinasas Activadas por Mitógenos/genética , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Extractos Vegetales/química , Transducción de Señal/efectos de los fármacos , Pez Cebra
15.
Clin Interv Aging ; 14: 1589-1599, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31564841

RESUMEN

Purpose: To explore the effects of 10 weeks of progressive vigorous interval training as a single intervention on health-related quality of life (HRQoL) and cardiometabolic risk markers in centrally obese 70-year-old individuals. Participants and methods: A randomized controlled trial (ClinicalTrials.gov registration no. NCT03450655) including seventy-seven community-dwelling 70-year-old men and women with central obesity defined as > 1 kg visceral adipose tissue for women and > 2 kg for men. Participants randomized to the intervention group were offered a 10-week progressive vigorous interval training program performed three times per week. Control subjects were asked to maintain their daily living and routines throughout the trial. All participants in both groups had received tailored lifestyle recommendations focused on diet and physical activity at one occasion within 12 months prior to trial initiation. Prespecified outcome measures included: changes in HRQoL using the Short Form Health Survey Questionnaire (SF-36), blood pressure; resting heart rate (HR) and blood lipids. All analyses were conducted on an intention-to-treat basis. Results: The intervention resulted in significant effects on the SF-36 mental component summary (MCS) score and the mental health (MH) subscale (P< 0.05 for both), when compared to the control group. Specifically, the intervention group increased their MCS score by 6.3 points (95% confidence interval [CI] = 0.3-12.3) and their MH score by 6.0 points (95% CI = 1.7-10.4) compared to the control group. Moreover, significant effects were seen on resting HR, total cholesterol and LDL-cholesterol (P<0.05 for all). Conclusion: It was shown that 10 weeks of vigorous interval training as a single intervention was sufficient to improve mental aspects of HRQoL in older individuals with central obesity, which is a critical aspect of healthy ageing. Positive effects were seen also on cardiometabolic risk markers.


Asunto(s)
Enfermedades Cardiovasculares/metabolismo , Ejercicio/psicología , Obesidad/terapia , Calidad de Vida/psicología , Circunferencia de la Cintura , Anciano , Enfermedades Cardiovasculares/prevención & control , Ejercicio/fisiología , Femenino , Humanos , Vida Independiente , Masculino , Encuestas y Cuestionarios , Resultado del Tratamiento
17.
J Clin Pathol ; 72(12): 785-799, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31611285

RESUMEN

Progresses in liquid-based assays may provide novel useful non-invasive indicators of cardiovascular (CV) diseases. By analysing circulating cells or their products in blood, saliva and urine samples, we can investigate molecular changes present at specific time points in each patient allowing sequential monitoring of disease evolution. For example, an increased number of circulating endothelial cells may be a diagnostic biomarker for diabetic nephropathy and heart failure with preserved ejection fraction. The assessment of circulating cell-free DNA (cfDNA) levels may be useful to predict severity of acute myocardial infarction, as well as diagnose heart graft rejection. Remarkably, circulating epigenetic biomarkers, including DNA methylation, histone modifications and non-coding RNAs are key pathogenic determinants of CV diseases representing putative useful biomarkers and drug targets. For example, the unmethylated FAM101A gene may specifically trace cfDNA derived from cardiomyocyte death providing a powerful diagnostic biomarker of apoptosis during ischaemia. Moreover, changes in plasma levels of circulating miR-92 may predict acute coronary syndrome onset in patients with diabetes. Now, network medicine provides a framework to analyse a huge amount of big data by describing a CV disease as a result of a chain of molecular perturbations rather than a single defect (reductionism). We outline advantages and challenges of liquid biopsy with respect to traditional tissue biopsy and summarise the main completed and ongoing clinical trials in CV diseases. Furthermore, we discuss the importance of combining fluid-based assays, big data and network medicine to improve precision medicine and personalised therapy in this field.


Asunto(s)
Líquidos Corporales/metabolismo , Enfermedades Cardiovasculares/diagnóstico , Técnicas de Diagnóstico Molecular , Medicina de Precisión , Biomarcadores/metabolismo , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/metabolismo , Ácidos Nucleicos Libres de Células/sangre , Toma de Decisiones Clínicas , Humanos , Biopsia Líquida , Selección de Paciente , Valor Predictivo de las Pruebas , Pronóstico , Reproducibilidad de los Resultados
18.
Anticancer Res ; 39(9): 4627-4635, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31519560

RESUMEN

In the clinical setting, administration of high daily or bolus doses of vitamin D is often solely based on 25-hydroxyvitamin D [25(OH)D] testing. This review summarizes the evidence of the effect of vitamin D on cardiovascular disease (CVD). Meta-analyses of randomized controlled trials (RCTs) have demonstrated that CVD risk markers, such as lipid parameters, inflammation markers, blood pressure, and arterial stiffness, are largely unaffected by vitamin D supplementation. Similar results have been obtained regarding CVD events and mortality from (meta)-analyses of RCTs, even in subgroups with 25(OH)D concentrations <50 nmol/l. Likewise, Mendelian randomization studies have indicated that the genetic reduction of the 25(OH)D concentration does not increase CVD risk. Some studies do not exclude the possibility of adverse vitamin D effects, such as elevated plasma calcium concentration and an increased CVD risk at a 25(OH)D concentration >125 nmol/l. Based on a conservative benefit-risk management approach, vitamin D doses beyond the nutritionally recommended amounts of 600 to 800 IE daily currently cannot be advised for the prevention of CVD events.


Asunto(s)
Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/metabolismo , Vitamina D/metabolismo , Animales , Biomarcadores , Enfermedades Cardiovasculares/epidemiología , Suplementos Dietéticos/efectos adversos , Sobredosis de Droga/complicaciones , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Factores de Riesgo , Vitamina D/administración & dosificación , Vitamina D/efectos adversos , Vitamina D/sangre , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/diagnóstico
19.
Toxicol Lett ; 317: 13-23, 2019 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-31562912

RESUMEN

Combination antiretroviral therapy (cART) has been hugely successful in reducing the mortality associated with human immunodeficiency virus (HIV) infection, resulting in a growing population of people living with HIV (PLWH). Since PLWH now have a longer life expectancy, chronic comorbidities have become the focus of the clinical management of HIV. For example, cardiovascular complications are now one of the most prevalent causes of death in PLWH. Numerous epidemiological studies show that antiretroviral treatment increases cardiovascular disease (CVD) risk and early onset of CVD in PLWH. Nucleoside reverse transcriptase inhibitors (NRTIs) are the backbone of cART, and two NRTIs are typically used in combination with one drug from another drug class, e.g., a fusion inhibitor. NRTIs are known to induce mitochondrial dysfunction, contributing to toxicity in numerous tissues, such as myopathy, lipoatrophy, neuropathy, and nephropathy. In in vitro studies, short-term NRTI treatment induces an endothelial dysfunction with an increased reactive oxygen species (ROS) production; long-term NRTI treatment decreases cell replication capacity, while increasing mtROS production and senescent cell accumulation. These findings suggest that a mitochondrial oxidative stress is involved in the pathogenesis of NRTI-induced endothelial dysfunction and premature senescence. Mitochondrial dysfunction, defined by a compromised mitochondrial quality control via biogenesis and mitophagy, has a causal role in premature endothelial senescence and can potentially initiate early cardiovascular disease (CVD) development in PLWH. In this review, we explore the hypothesis and present literature supporting that long-term NRTI treatment induces vascular dysfunction by interfering with endothelial mitochondrial homeostasis and provoking mitochondrial genomic instability, resulting in premature endothelial senescence.


Asunto(s)
Fármacos Anti-VIH/efectos adversos , Enfermedades Cardiovasculares/inducido químicamente , Senescencia Celular/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Infecciones por VIH/tratamiento farmacológico , Mitocondrias/efectos de los fármacos , Animales , Fármacos Anti-VIH/administración & dosificación , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/patología , Esquema de Medicación , Células Endoteliales/metabolismo , Células Endoteliales/patología , Metabolismo Energético/efectos de los fármacos , Infecciones por VIH/metabolismo , Infecciones por VIH/patología , Humanos , Mitocondrias/metabolismo , Mitocondrias/patología , Medición de Riesgo , Transducción de Señal/efectos de los fármacos , Factores de Tiempo
20.
Nat Commun ; 10(1): 4329, 2019 09 24.
Artículo en Inglés | MEDLINE | ID: mdl-31551469

RESUMEN

Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10-8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD.


Asunto(s)
Enfermedades Cardiovasculares/metabolismo , Lípidos/genética , Plasma/metabolismo , Enfermedades Cardiovasculares/genética , Estudio de Asociación del Genoma Completo , Humanos
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