RESUMO
Abstract Arterial hypertension is the most important cardiovascular risk factor in chronic non-communicable diseases and is estimated to be responsible for 10.4 million deaths annually. The global prevalence of hypertension is 30% and the majority of people with hypertension do not have a clear identifiable cause and are considered to have primary hypertension. Experimental and clinical investigations from several research groups, including ours, have established that inflammation and autoimmune reactivity play a role in the sodium retention and hemodynamic responses that drive primary hypertension. Hyperuricemia and heat stress proteins (HSP), particularly HSP70, are both associated with the activation of innate immunity that plays a role in the development of inflammatory reactivity in the hypertensive patient. Clinical studies have shown an association between the expression of HSP70 and anti-HSP70 antibodies and primary hypertension. This brief review aims to examine the interrelation between hyperuricemia and extracellular overexpression of HSP70 in the activation of the inflammasome that may have a central role in the pathophysiology of primary hypertension.
Resumen La hipertensión arterial es el factor de riesgo cardiovascular más importante de las enfermedades crónicas no transmisibles y se estima que es responsable de 10.4 millones de muertes al año. La prevalencia mundial de la hipertensión es del 30%; la mayoría de las personas con hipertensión no tienen una causa claramente identificable y se considera que tienen hipertensión primaria. Las investigaciones experimentales y clínicas de varios grupos de investigación, incluido el nuestro, han establecido que la inflamación y la reactividad autoinmune desempeñan un papel en la retención de sodio y las respuestas hemodinámicas que provocan la hipertensión primaria. La hiperuricemia y las proteínas del estrés por calor (HSP), particularmente HSP70, están asociadas con la activación de la inmunidad innata que juega un papel en el desarrollo de la reactividad inflamatoria en pacientes hipertensos. Estudios clínicos han demostrado asociación entre la expresión de HSP70 y anticuerpos anti-HSP70 y la hipertensión arterial primaria Esta breve revisión tiene como objetivo examinar la interrelación entre la hiperuricemia y la sobreexpresión extracelular de HSP70 en la activación del inflamasoma, así como su probable papel central en la fisiopatología de la hipertensión primaria.
RESUMO
Arterial hypertension is the most important cardiovascular risk factor in chronic non-communicable diseases and is estimated to be responsible for 10.4 million deaths annually. The global prevalence of hypertension is 30% and the majority of people with hypertension do not have a clear identifiable cause and are considered to have primary hypertension. Experimental and clinical investigations from several research groups, including ours, have established that inflammation and autoimmune reactivity play a role in the sodium retention and hemodynamic responses that drive primary hypertension. Hyperuricemia and heat stress proteins (HSP), particularly HSP70, are both associated with the activation of innate immunity that plays a role in the development of inflammatory reactivity in the hypertensive patient. Clinical studies have shown an association between the expression of HSP70 and anti-HSP70 antibodies and primary hypertension. This brief review aims to examine the interrelation between hyperuricemia and extracellular overexpression of HSP70 in the activation of the inflammasome that may have a central role in the pathophysiology of primary hypertension.
La hipertensión arterial es el factor de riesgo cardiovascular más importante de las enfermedades crónicas no transmisibles y se estima que es responsable de 10.4 millones de muertes al año. La prevalencia mundial de la hipertensión es del 30%; la mayoría de las personas con hipertensión no tienen una causa claramente identificable y se considera que tienen hipertensión primaria. Las investigaciones experimentales y clínicas de varios grupos de investigación, incluido el nuestro, han establecido que la inflamación y la reactividad autoinmune desempeñan un papel en la retención de sodio y las respuestas hemodinámicas que provocan la hipertensión primaria. La hiperuricemia y las proteínas del estrés por calor (HSP), particularmente HSP70, están asociadas con la activación de la inmunidad innata que juega un papel en el desarrollo de la reactividad inflamatoria en pacientes hipertensos. Estudios clínicos han demostrado asociación entre la expresión de HSP70 y anticuerpos anti-HSP70 y la hipertensión arterial primaria Esta breve revisión tiene como objetivo examinar la interrelación entre la hiperuricemia y la sobreexpresión extracelular de HSP70 en la activación del inflamasoma, así como su probable papel central en la fisiopatología de la hipertensión primaria.
Assuntos
Hipertensão , Hiperuricemia , Humanos , Hipertensão Essencial , Proteínas de Choque Térmico HSP70/metabolismo , Hipertensão/epidemiologia , Hiperuricemia/complicações , Hiperuricemia/epidemiologia , Inflamassomos/metabolismo , Inflamação , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismoRESUMO
Despite its discovery more than 150 years ago, the cause of primary hypertension remains unknown. Most studies suggest that hypertension involves genetic, congenital or acquired risk factors that result in a relative inability of the kidney to excrete salt (sodium chloride) in the kidneys. Here we review recent studies that suggest there may be two phases, with an initial phase driven by renal vasoconstriction that causes low-grade ischemia to the kidney, followed by the infiltration of immune cells that leads to a local autoimmune reaction that maintains the renal vasoconstriction. Evidence suggests that multiple mechanisms could trigger the initial renal vasoconstriction, but one way may involve fructose that is provided in the diet (such as from table sugar or high fructose corn syrup) or produced endogenously. The fructose metabolism increases intracellular uric acid, which recruits NADPH oxidase to the mitochondria while inhibiting AMP-activated protein kinase. A drop in intracellular ATP level occurs, triggering a survival response. Leptin levels rise, triggering activation of the sympathetic central nervous system, while vasopressin levels rise, causing vasoconstriction in its own right and stimulating aldosterone production via the vasopressin 1b receptor. Low-grade renal injury and autoimmune-mediated inflammation occur. High-salt diets can amplify this process by raising osmolality and triggering more fructose production. Thus, primary hypertension may result from the overactivation of a survival response triggered by fructose metabolism. Restricting salt and sugar and hydrating with ample water may be helpful in the prevention of primary hypertension.
RESUMO
Asthma is a chronic inflammatory disease in the airways with a multifactorial origin but with inflammation and oxidative stress as related pathogenic mechanisms. Garlic (Allium sativum) is a nutraceutical with different biological properties due to sulfur-containing natural compounds. Studies have shown that several compounds in garlic may have beneficial effects on cardiovascular diseases, including those related to the lungs. Therefore, it is possible to take advantage of the compounds from garlic as nutraceuticals for treating lung diseases. The objective of this article is to review the biological properties of the sulfur compounds present in garlic for the treatment of asthma, as well as the cellular mechanisms involved. Here, we discuss the potential therapeutic effects of garlic compounds in the modulation of inflammation and oxidative stress, as well as its antibiotic and antiviral activities for identifying and testing potential treatment options for asthma management.
Assuntos
Asma , Alho , Humanos , Compostos de Enxofre/farmacologia , Antioxidantes/farmacologia , Asma/tratamento farmacológico , Estresse Oxidativo , Inflamação/tratamento farmacológico , Extratos Vegetais/farmacologiaRESUMO
Resumen Las enfermedades cardiovasculares (ECV) comprenden un grupo de enfermedades cuyo denominador común es la afectación de vasos sanguíneos, corazón y ritmo cardiaco. El tratamiento de las ECV representa costos muy altos para los sistemas de salud y está enfocado en el control de los factores de riesgo. A pesar de existir una gran variedad de fármacos para el tratamiento de las ECV, estas continúan siendo las principales causas de mortalidad, posiblemente debido a que su origen es multifactorial y por ello se requiere de más de un fármaco. En este contexto, la alicina, un compuesto derivado del ajo, ha mostrado regular la expresión de vías de señalización y factores de riesgo asociados a la progresión de las ECV. Por ello el objetivo del presente trabajo es revisar los mecanismos celulares y moleculares por medio de los cuales la alicina ejerce sus efectos terapéuticos y describir las evidencias científicas del porqué la alicina podría representar un potencial candidato para coadyuvar en el tratamiento de las ECV.
Abstract Cardiovascular diseases (CVD) include a group of diseases whose common denominator is the affection of the blood vessels, heart, and heart rate. The treatment of CVD represents high costs to the health systems and is focused on the control of risk factors. Despite the existence of a great variety of treatments of the CVD, these continue as the main cause of mortality mainly due to the multifactorial origin, and therefore more than one drug is required. In this context, allicin, a compound derived from garlic, has shown regulate the expression of signaling pathways and risk factors associated with the progression of CVD. Therefore, the objective of this work is to review the cellular and molecular mechanisms through which allicin exert its therapeutic effects and to describe the scientific evidences why allicin represents a potential candidate to assist in the treatment of CVD.
RESUMO
Cardiovascular diseases (CVDs) are a group of diseases in which the common denominator is the affection of blood vessels, heart tissue, and heart rhythm. The genesis of CVD is complex and multifactorial; therefore, approaches are often based on multidisciplinary management and more than one drug is used to achieve the optimal control of risk factors (dyslipidemia, hypertension, hypertrophy, oxidative stress, endothelial dysfunction, inflammation). In this context, allicin, a sulfur compound naturally derived from garlic, has shown beneficial effects on several cardiovascular risk factors through the modulation of cellular mechanisms and signaling pathways. Effective pharmacological treatments for CVD or its risk factors have not been developed or are unknown in clinical practice. Thus, this work aimed to review the cellular mechanisms through which allicin exerts its therapeutic effects and to show why it could be a therapeutic option for the prevention or treatment of CVD and its risk factors.
Assuntos
Doenças Cardiovasculares , Alho , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Dissulfetos/uso terapêutico , Humanos , Ácidos Sulfínicos/farmacologia , Ácidos Sulfínicos/uso terapêuticoRESUMO
Las enfermedades cardiovasculares (ECV) comprenden un grupo de enfermedades cuyo denominador común es la afectación de vasos sanguíneos, corazón y ritmo cardiaco. El tratamiento de las ECV representa costos muy altos para los sistemas de salud y está enfocado en el control de los factores de riesgo. A pesar de existir una gran variedad de fármacos para el tratamiento de las ECV, estas continúan siendo las principales causas de mortalidad, posiblemente debido a que su origen es multifactorial y por ello se requiere de más de un fármaco. En este contexto, la alicina, un compuesto derivado del ajo, ha mostrado regular la expresión de vías de señalización y factores de riesgo asociados a la progresión de las ECV. Por ello el objetivo del presente trabajo es revisar los mecanismos celulares y moleculares por medio de los cuales la alicina ejerce sus efectos terapéuticos y describir las evidencias científicas del porqué la alicina podría representar un potencial candidato para coadyuvar en el tratamiento de las ECV.Cardiovascular diseases (CVD) include a group of diseases whose common denominator is the affection of the blood vessels, heart, and heart rate. The treatment of CVD represents high costs to the health systems and is focused on the control of risk factors. Despite the existence of a great variety of treatments of the CVD, these continue as the main cause of mortality mainly due to the multifactorial origin, and therefore more than one drug is required. In this context, allicin, a compound derived from garlic, has shown regulate the expression of signaling pathways and risk factors associated with the progression of CVD. Therefore, the objective of this work is to review the cellular and molecular mechanisms through which allicin exert its therapeutic effects and to describe the scientific evidences why allicin represents a potential candidate to assist in the treatment of CVD.
Assuntos
Doenças Cardiovasculares , Doenças Cardiovasculares/epidemiologia , Humanos , Estudos Retrospectivos , Fatores de RiscoRESUMO
Fructose metabolism and hyperuricemia have been shown to drive insulin resistance, metabolic syndrome, hepatic steatosis, hypertension, inflammation, and innate immune reactivity in experimental studies. We suggest that these adverse effects are at least in part the result of suppressed activity of sirtuins, particularly Sirtuin1. Deficiency of sirtuin deacetylations is a consequence of reduced bioavailability of its cofactor nicotinamide adenine dinucleotide (NAD+). Uric acid-induced inflammation and oxidative stress consume NAD+ and activation of the polyol pathway of fructose and uric acid synthesis also reduces the NAD+-to-NADH ratio. Variability in the compensatory regeneration of NAD+ could result in variable recovery of sirtuin activity that may explain the inconsistent benefits of treatments directed to reduce uric acid in clinical trials. Here, we review the pathogenesis of the metabolic dysregulation driven by hyperuricemia and their potential relationship with sirtuin deficiency. In addition, we discuss therapeutic options directed to increase NAD+ and sirtuins activity that may improve the adverse effects resulting from fructose and uric acid synthesis.
Assuntos
Resistência à Insulina , Sirtuínas , Frutose/efeitos adversos , Frutose/metabolismo , Humanos , NAD/metabolismo , Sirtuínas/metabolismo , Ácido ÚricoRESUMO
Abstract Hyperuricemia is common in chronic kidney disease (CKD) and may be present in 50% of patients presenting for dialysis. Hyperuricemia can be secondary to impaired glomerular filtration rate (GFR) that occurs in CKD. However, hyperuricemia can also precede the development of kidney disease and predict incident CKD. Experimental studies of hyperuricemic models have found that both soluble and crystalline uric acid can cause significant kidney damage, characterized by ischemia, tubulointerstitial fibrosis, and inflammation. However, most Mendelian randomization studies failed to demonstrate a causal relationship between uric acid and CKD, and clinical trials have had variable results. Here we suggest potential explanations for the negative clinical and genetic findings, including the role of crystalline uric acid, intracellular uric acid, and xanthine oxidase activity in uric acid-mediated kidney injury. We propose future clinical trials as well as an algorithm for treatment of hyperuricemia in patients with CKD.
Resumo A hiperuricemia é comum na doença renal crônica (DRC) e pode estar presente em até 50% dos pacientes que se apresentam para diálise. A hiperuricemia pode ser secundária ao comprometimento da taxa de filtração glomerular (TFG) que ocorre na DRC. No entanto, ela também pode preceder o desenvolvimento da doença renal e mesmo prever uma DRC incidente. Estudos experimentais de modelos hiperuricêmicos descobriram que tanto o ácido úrico solúvel quanto o cristalino podem causar danos renais significativos, caracterizados por isquemia, fibrose tubulointersticial e inflamação. Entretanto, a maioria dos estudos de randomização Mendeliana falhou em demonstrar uma relação causal entre o ácido úrico e a DRC, e os ensaios clínicos têm apresentado resultados variáveis. Aqui sugerimos explicações potenciais para os achados clínicos e genéticos negativos, incluindo o papel do ácido úrico cristalino, do ácido úrico intracelular e da atividade da xantina oxidase na lesão renal mediada por ácido úrico. Propomos ensaios clínicos futuros, bem como um algoritmo para o tratamento de hiperuricemia em pacientes com DRC.
Assuntos
Humanos , Hiperuricemia/complicações , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Ácido Úrico , Diálise Renal , Taxa de Filtração GlomerularRESUMO
Hyperuricemia is common in chronic kidney disease (CKD) and may be present in 50% of patients presenting for dialysis. Hyperuricemia can be secondary to impaired glomerular filtration rate (GFR) that occurs in CKD. However, hyperuricemia can also precede the development of kidney disease and predict incident CKD. Experimental studies of hyperuricemic models have found that both soluble and crystalline uric acid can cause significant kidney damage, characterized by ischemia, tubulointerstitial fibrosis, and inflammation. However, most Mendelian randomization studies failed to demonstrate a causal relationship between uric acid and CKD, and clinical trials have had variable results. Here we suggest potential explanations for the negative clinical and genetic findings, including the role of crystalline uric acid, intracellular uric acid, and xanthine oxidase activity in uric acid-mediated kidney injury. We propose future clinical trials as well as an algorithm for treatment of hyperuricemia in patients with CKD.