Potencial rol protector del óxido nítrico y Hsp70 asociado a alimentos funcionales en la aterosclerosis

doi:10.1016/j.arteri.2016.05.004

Clínica e Investigación en Arteriosclerosis

Volume 29, Issue 1, January–February 2017, Pages 36-45

https://doi.org/10.1016/j.arteri.2016.05.004 Get rights and content

Resumen

En la actualidad se encuentran en constante revisión los mecanismos determinantes primarios y las posibles terapéuticas de una de las principales entidades patológicas considerada epidémica y constituida como problema de salud pública mundial: la aterosclerosis. En tal sentido, pacientes que la padecen presentan como común denominador disfunción mitocondrial, estrés oxidativo e inflamación. De especial interés, el óxido nítrico, un conocido gas mensajero vasoactivo, ha sido estrechamente relacionado con el proceso inflamatorio, oxidativo y disfuncional mitocondrial propio de la aterosclerosis. Por otro lado, muy recientemente se ha demostrado que alteraciones en la biodisponibilidad del óxido nítrico inducirían la expresión de proteínas de shock térmico. Este mecanismo sería inducido también por el uso de los denominados alimentos funcionales como estrategia para prevenir el envejecimiento vascular así como el desarrollo de aterosclerosis. Finalmente, el mayor conocimiento de los mecanismos implicados en el desarrollo de la aterosclerosis nos permitirá proponer nuevas y posibles intervenciones higiénicas, sanitarias y terapéuticas.

Abstract

Atherosclerosis, one of the main pathologic entities considered epidemic and a worldwide public health problem, is currently under constant review as regards its basic determining mechanisms and therapeutic possibilities. In this regard, all patients afflicted with the disease exhibit mitochondrial dysfunction, oxidative stress and inflammation. Interestingly, nitric oxide — a known vasoactive messenger gas — has been closely related to the inflammatory, oxidative and mitochondrial dysfunctional process that characterizes atherosclerosis. In addition, it has recently been demonstrated that alterations in the bioavailability of nitric oxide would induce the expression of heat shock proteins. This agrees with the use of functional foods as a strategy to prevent both vascular aging and the development of atherosclerosis. Finally, a greater knowledge regarding the mechanisms implied in the development of atherosclerosis will enable proposing new and possible hygiene, health and therapeutic interventions.

Section snippets

Introducción

La ateroesclerosis como entidad patológica emergente en los países industrializados responde a un síndrome caracterizado por el depósito y la infiltración de sustancias lipídicas en las paredes de las arterias de mediano y grueso calibre. Además, provoca inflamación, multiplicación y migración de las células musculares lisas condicionando el estrechamiento de la luz arterial¹, para finalmente conducir a la aparición de enfermedades cardiovasculares (ECV). En el proceso inflamatorio crónico

Óxido nítrico y Hsp70 en aterosclerosis

El NO, una especie reactiva del nitrógeno de vida media ultracorta, participa como factor regulador de una diversa gama de funciones fisiológicas como el control de la resistencia vascular, la neurotransmisión y la modulación de procesos inflamatorios, entre otras11, 26, 27, 28, 29, 30. Bioquímicamente y a nivel citosólico, el NO es una molécula sintetizada por enzimas NOS con L-arginina, NADPH y O₂ como sustratos básicos³¹. Por otro lado, también se ha descrito una producción mitocondrial

Alimentos funcionales y salud cardiovascular

Si bien el concepto de alimentos funcionales fue introducido, es menester destacar que en la actualidad existen controversias respecto a trazar una línea que precise las características específicas de este grupo de alimentos que los diferencien del resto. En consecuencia, no se encuentra una definición de alimentos funcionales que sea universalmente aceptada y, por lo tanto, son escasas las regulaciones específicas en países de occidente⁶³. Diferente es la situación en oriente, donde los

Alimentos funcionales, óxido nítrico y Hsp70 en aterosclerosis

El estado de conocimiento actual discute sobre las múltiples causas de la enfermedad ateroesclerótica; sin embargo, la inflamación y el estrés oxidativo juegan un papel fundamental en la patogénesis de la disfunción endotelial que se atribuye comúnmente a una alteración en la disponibilidad de NO. En adición, Hsp70 protegería a los elementos celulares de la lesión mediante la reducción de la oxidación, la inflamación y la apoptosis⁸¹. Por lo tanto, existen evidencias concretas que sugieren al

Conclusiones y perspectivas

El estado de conocimiento actual reconoce un importante número de causas de la enfermedad ateroesclerótica. Sin embargo, la inflamación y el estrés oxidativo destacan como determinantes fundamentales en la patogénesis de la disfunción endotelial atribuida comúnmente a una alteración en la disponibilidad de NO. En adición, Hsp70 protegería a los elementos celulares de la lesión mediante la reducción de la oxidación, la inflamación y la apoptosis. De interés, se encuentran en constante revisión

Protección de personas y animales

Los autores declaran que para esta investigación no se han realizado experimentos en seres humanos ni en animales.

Confidencialidad de los datos

Los autores declaran que han seguido los protocolos de su centro de trabajo sobre la publicación de datos de pacientes.

Derecho a la privacidad y consentimiento informado

Los autores declaran que en este artículo no aparecen datos de pacientes.

Conflicto de intereses

Los autores declaran no tener ningún conflicto de intereses potencial con respecto a la investigación, la autoría y/o la publicación de este artículo de revisión.

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Anti-inflammatory, antioxidant, antihypertensive, and antiarrhythmic effect of indole-3-carbinol, a phytochemical derived from cruciferous vegetables
2022, Heliyon
Citation Excerpt :
Recent research suggests this signaling pathway as a valid hypothesis that justifies the use of so-called functional foods as a strategy to prevent vascular aging and the development of atherosclerosis (Kitada et al., 2016). Functional foods stand out for their high content of active compounds (phytochemicals) and show beneficial properties in relation to health (Camargo and Manucha, 2017). One of these compounds is indole-3-carbinol (I3C), which is found in vegetables belonging to the cruciferous genus, such as broccoli and cabbage (Licznerska and Baer-Dubowska, 2016).
Cardiovascular inflammation and oxidative stress are determining factors in high blood pressure and arrhythmias. Indole-3-carbinol is a cruciferous-derived phytochemical with potential anti-inflammatory and antioxidant effects. However, its implications on the modulation of cardiovascular inflammatory-oxidative markers are unknown.
To establish the effects of indole-3-carbinol on the oxidative-inflammatory-proarrhythmic conditions associated with hypertension.
Histological, biochemical, molecular, and functional aspects were evaluated in 1) Culture of mouse BV-2 glial cells subjected to oxidative-inflammatory damage by lipopolysaccharides (100 ng/mL) in the presence or absence of 40 μM indole-3-carbinol (n = 5); 2) Male spontaneously hypertensive rats (SHR) and Wistar Kyoto rats receiving indole-3-carbinol (2000 ppm/day, orally) during the first 8 weeks of life (n = 15); 3) Isolated rat hearts were submitted to 10 min regional ischemia and 10 min reperfusion.
1) lipopolysaccharides induced oxidative stress and increased inflammatory markers; indole-3-carbinol reversed both conditions (interleukin 6, tumor necrosis factor α, the activity of nicotinamide adenine dinucleotide phosphate oxidase, nitric oxide, inducible nitric oxide synthase, heat shock protein 70, all p < 0.01 vs lipopolysaccharides). 2) SHR rats showed histological, structural, and functional changes with increasing systolic blood pressure (154 ± 8 mmHg vs. 122 ± 7 mmHg in Wistar Kyoto rats, p < 0.01); Inflammatory-oxidative markers also increased, and nitric oxide and heat shock protein 70 decreased. Conversely, indole-3-carbinol reduced oxidative-inflammatory markers and systolic blood pressure (133 ± 8 mmHg, p < 0.01 vs. SHR). 3) indole-3-carbinol reduced reperfusion arrhythmias from 8/10 in SHR to 0/10 (p = 0.0007 by Fisher's exact test).
Indole-3-carbinol reduces the inflammatory-oxidative-proarrhythmic process of hypertension. The nitric oxide and heat shock protein 70 are relevant mechanisms of indole-3-carbinol protective actions. Further studies with this pleiotropic phytochemical as a promising cardioprotective are guaranteed.
Phytochemical profile and functionality of Brassicaceae species
2020, Food Bioscience
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Some authors have reported that ITC can lower the incidences of different cancers (Dinkova-Kostova & Kostov, 2012). The chemopreventive properties of ITC are shown by their participation in multiple anticancer mechanisms such as modifications of the chemical carcinogenesis process due to changes in the activities of drug-metabolizing enzymes, induction of cell cycle arrest and apoptosis, inhibition of angiogenesis and metastasis, changes in histone acetylation status, as well as antioxidant, anti-inflammatory, and immunomodulatory activities (Camargo & Manucha, 2016; Dinkova-Kostova & Kostov, 2012). The characterization of the ITC's antioxidant properties is significant because they may protect the human body against the oxidative damage mediated by reactive oxygen species (ROS).
The most widely consumed Brassicaceae species were characterized and compared in the present study. The isothiocyanates and phenolic profiles were measured. The in vitro antioxidant and antiradical activities were determined using 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid diammonium salt, 1,1-diphenyl-2-picrylhydrazyl radical, ferric reducing antioxidant potential and β-carotene methods. The results showed that all Brassicaceae species evaluated had antioxidant properties, with watercress and green mustard being the most active antioxidant species. Every vegetable studied had a unique sulfur and phenolic profile. Twenty-five phytochemicals were found in Brassicaceae species and their antioxidant activity measured using pure compounds. The results showed that the strongest antioxidant compounds in decreasing order were myricetin, quercetin-3-galactoside, quercetin-3-glucoside, pterostilbene, ferulic acid, kaempferol, allyl isothiocyanate, and (-)-epicatechin. Besides, the phenolic compound trans-resveratrol was found in these species. The highest concentration of trans-resveratrol was observed in rocket leaves at up to 84 μg/g dry weight.
Allicin pharmacology: Common molecular mechanisms against neuroinflammation and cardiovascular diseases
2020, Life Sciences
Citation Excerpt :
OSCs increase the expression of HSPs as part of its antioxidant protective effect [8]. For example, our laboratory has previously discussed the potential protective role of HSP70 linked to functional foods in atherosclerosis [110]. In addition to its known classic antioxidant effects, the mitochondrial protection associated with HSP70 supports an additional mechanism that involves translocase of the outer mitochondrial membrane 70 (TOM70), with the mitochondrial function being required to correct HSP70 interaction with TOM70 [111].
According to investigations in phytomedicine and ethnopharmacology, the therapeutic properties of garlic (Allium sativum) have been described by ancestral cultures. Notwithstanding, it is of particular concern to elucidate the molecular mechanisms underlying this millenary empirical knowledge. Allicin (S-allyl prop-2-ene-1-sulfinothioate), a thioester of sulfenic acid, is one of the main bioactive compounds present in garlic, and it is responsible for the particular aroma of the spice. The pharmacological attributes of allicin integrate a broad spectrum of properties (e.g., anti-inflammatory, immunomodulatory, antibiotic, antifungal, antiparasitic, antioxidant, nephroprotective, neuroprotective, cardioprotective, and anti-tumoral activities, among others). The primary goal of the present article is to review and clarify the common molecular mechanisms by which allicin and its derivates molecules may perform its therapeutic effects on cardiovascular diseases and neuroinflammatory processes. The intricate interface connecting the cardiovascular and nervous systems suggests that the impairment of one organ could contribute to the dysfunction of the other. Allicin might target the cornerstone of the pathological processes underlying cardiovascular and neuroinflammatory disorders, like inflammation, renin-angiotensin-aldosterone system (RAAS) hyperactivation, oxidative stress, and mitochondrial dysfunction. Indeed, the current evidence suggests that allicin improves mitochondrial function by enhancing the expression of HSP70 and NRF2, decreasing RAAS activation, and promoting mitochondrial fusion processes. Finally, allicin represents an attractive therapeutic alternative targeting the complex interaction between cardiovascular and neuroinflammatory disorders.
Heat shock protein 70 accelerates atherosclerosis by downregulating the expression of ABCA1 and ABCG1 through the JNK/Elk-1 pathway
2018, Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Citation Excerpt :
For instance, the levels of HSP70, HSP65, and HSP27 are all increased in patients with vascular disease [51,55,57]. It has been reported that HSP70 accelerates the progression of atherosclerosis [30,55,56,58,59]. However, the detailed underlying mechanisms, especially the potential effects of HSP70 on lipid metabolism and RCT and the related pathogenesis of atherosclerosis, have yet to be determined.
Recent studies have suggested that heat shock protein 70 (HSP70) may play critical roles in cardiovascular disease. However, the effects of HSP70 on the development of atherosclerosis in apoE^−/− mice remain largely unknown. This study was to investigate the role and potential mechanism of HSP70 in atherosclerosis.
HSP70 was overexpressed in apoE^−/− mice and THP-1-derived macrophages with lentiviral vectors. Oil Red O, hematoxylin-eosin, and Masson staining were performed to evaluate atherosclerotic plaque in apoE^−/− mice fed the Western type diet. Moreover, immunostaining was employed to detect the expression of relative proteins in aortic sinus. Reporter gene and chromatin immunoprecipitation were performed to analyze the effect of Elk-1 on the promoter activity of ABCA1 and ABCG1; [³H] labeled cholesterol was used to assess the capacity of cholesterol efflux and reverse cholesterol transport (RCT).
Our results showed that HSP70 increased lipid accumulation in arteries and promoted the formation of atherosclerotic lesion. The capacity of cholesterol efflux was reduced in peritoneal macrophages isolated from HSP70-overexpressed apoE^−/− mice. The levels of ABCA1 and ABCG1 expression were also reduced in the peritoneal macrophages and the aorta from apoE^−/− mice in response to HSP70. The c-Jun N-terminal kinase (JNK) and ETS transcription factor (Elk-1) played a critical role in HSP70-induced downregulation ABCA1 and ABCG1. Further, HSP70 reduced RCT from macrophages to plasma, liver, and feces in apoE^−/− mice.
HSP70 promotes the progression of atherosclerosis in apoE^−/− mice by suppressing the expression of ABCA1 and ABCG1 through the JNK/Elk-1 pathway.
Analytical methods for bioactive sulfur compounds in Allium: An integrated review and future directions
2017, Journal of Food Composition and Analysis
Citation Excerpt :
Garlic consumption is associated with decreased risk of some types of cancer, particularly those of the gastrointestinal tract (Guercio et al., 2014; Nicastro et al., 2015; Omar and Al-Wabel, 2010). Preclinical and clinical evidence demonstrated that garlic consumption can reduce risks associated with cardiovascular diseases (CVD), by lowering cholesterol level, inhibiting platelet aggregation, and lowering blood pressure (Bradley et al., 2016; Camargo and Manucha, 2016; Cavagnaro et al., 2007; Sikand et al., 2015). In addition to these cancer- and cardio-protective effects, various other biological activities have been reported for garlic, including antimicrobial, antioxidant, and anti-inflammatory properties (Block, 2010; Borlinghaus et al., 2014; Charu et al., 2014; Suvarna and Rajagopalan, 2015).
Plant organosulfur compounds represent one of the main groups of phytochemicals that evidence an ample spectrum of biological activities. There are two major sources of sulfur-containing compounds in plant foods; Allium vegetables, such as garlic, onion, and leek; and cruciferous vegetables, such as broccoli, cabbage, and cauliflower. Among them, garlic is the most studied species, mainly due to the multiple health-enhancing effects attributed to its consumption. Most of these properties have been attributed to organosulfur compounds. Thus, knowledge on the analytical determinations available for the main bioactive sulfur compounds in Allium is of interest. In the present review, an extensive bibliographic survey was performed to compile information regarding the different methodologies that can be used for the determination of alk(en)yl cysteine sulfoxides (ACSOs), S-allyl cysteine (SAC), thiosulfinates (mainly allicin), diallyl, mono- di-, and tri-sulfides, vinyldithiins and (E)- and (Z)-ajoene, as influenced by plant matrices and other factors. The gathered information was analyzed and presented in a systemic and comparative way, describing advantages and disadvantages of the methodologies, considering both extractive and separative techniques, the type of matrices, columns and analytical performance data. In addition, new trends and future prospects for the analysis of sulfur compounds in plants were critically discussed.
Chaperone duality: the role of extracellular and intracellular HSP70 as a biomarker of endothelial dysfunction in the development of atherosclerosis
2022, Archives of Physiology and Biochemistry

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RevisiónPotencial rol protector del óxido nítrico y Hsp70 asociado a alimentos funcionales en la aterosclerosisPotential protective role of nitric oxide and Hsp70 linked to functional foods in the atherosclerosis

Resumen

Abstract

Section snippets

Introducción

Óxido nítrico y Hsp70 en aterosclerosis

Alimentos funcionales y salud cardiovascular

Alimentos funcionales, óxido nítrico y Hsp70 en aterosclerosis

Conclusiones y perspectivas

Protección de personas y animales

Confidencialidad de los datos

Derecho a la privacidad y consentimiento informado

Conflicto de intereses

J Lipid Res.

Clin Biochem.

Vascul Pharmacol.

Int J Cardiol.

Cell Stress Chaperones.

Cell Stress Chaperones.

Gastroenterology.

Clin Biochem.

Nitric Oxide.

J Biol Chem.

Biochim Biophys Acta.

Brain Res.

Endocrinol Metab Clin N Am.

Kidney Int.

Kidney Int.

Kidney Int.

Nitric Oxide.

Cell Stress Chaperones.

Cell Stress Chaperones.

Cell Stress Chaperones.

Cell Stress Chaperones.

Clin Biochem.

Atherosclerosis.

Appetite.

J Nutr.

J Funct Foods.

Phytochemistry.

J Funct Foods.

Am J Clin Nutr.

Nutr Res.

Life Sci.

J Nutr.

Atherosclerosis

Mol Aspects Med.

Eur J Pharmacol.

Global burden of cardiovascular diseases. Part I: General considerations, the epidemiologic transition, risk factors, and impact of urbanization

Circulation.

Cohort profile: The Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) study

Int J Epidemiol.

Consolidated and emerging inflammatory markers in coronary artery disease

World J Exp Med.

Obesity, hypertension and hypercholesterolemia as risk factors for atherosclerosis leading to ischemic events

Curr Med Chem.

Mitochondrial oxidative stress, mitochondrial DNA damage and their role in age-related vascular dysfunction

Int J Mol Sci.

Metabolic syndrome, aging and involvement of oxidative stress

Aging Dis.

S-Nitrosylation and uncompetitive/fast off-rate (UFO) drug therapy in neurodegenerative disorders of protein misfolding

Cell Death Differ.

Mechanisms of hepatoprotection by nitric oxide

Ann N Y Acad Sci.

Recent advances in gastrointestinal pathophysiology: Role of heat shock proteins in mucosal defense and ulcer healing

Biol Pharm Bull.

Heat shock proteins: Mediators of atherosclerotic development

Curr Drug Targets.

Mediterranean nutraceutical foods: Strategy to improve vascular ageing

Mech Ageing Dev.

Health effects of changes in the structure of dietary macronutrients intake in western societies

Rocz Panstw Zakl Hig.

Revisión
Potencial rol protector del óxido nítrico y Hsp70 asociado a alimentos funcionales en la aterosclerosisPotential protective role of nitric oxide and Hsp70 linked to functional foods in the atherosclerosis