Lipoic acid, but not tempol, preserves vascular compliance and decreases medial calcification in a model of elastocalcinosis

Bassi, Estêvão; Liberman, Marcel; Martinatti, Marina K; Bortolotto, Luiz Aparecido; Laurindo, Francisco Rafael Martins

doi:10.1590/1414-431x20133193

Cited by 6 publications

(5 citation statements)

References 30 publications

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“…Parallel reading of images was performed with identical laser acquisition settings. Control samples were preincubated with superoxide dismutase-polyethylene glycol (PEG-SOD) (500 U/mL for 7 min) to confirm the fluorescent signal as due to superoxide production [ 34 ].…”

Section: Methodsmentioning

confidence: 99%

Effect of the Antioxidant Lipoic Acid in Aortic Phenotype in a Marfan Syndrome Mouse Model

Guido

Debbas

Salemi

et al. 2018

Oxidative Medicine and Cellular Longevity

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Marfan syndrome (MFS) cardiovascular manifestations such as aortic aneurysms and cardiomyopathy carry substantial morbidity/mortality. We investigated the effects of lipoic acid, an antioxidant, on ROS production and aortic remodeling in a MFS mgΔloxPneo mouse model. MFS and WT (wild-type) 1-month-old mice were allocated to 3 groups: untreated, treated with losartan, and treated with lipoic acid. At 6 months old, echocardiography, ROS production, and morphological analysis of aortas were performed. Aortic ROS generation in 6-month-old MFS animals was higher at advanced stages of disease in MFS. An unprecedented finding in MFS mice analyzed by OCT was the occurrence of focal inhomogeneous regions in the aortic arch, either collagen-rich extremely thickened or collagen-poor hypotrophic regions. MFS animals treated with lipoic acid showed markedly reduced ROS production and lower ERK1/2 phosphorylation; meanwhile, aortic dilation and elastic fiber breakdown were unaltered. Of note, lipoic acid treatment associated with the absence of focal inhomogeneous regions in MFS animals. Losartan reduced aortic dilation and elastic fiber breakdown despite no change in ROS generation. In conclusion, oxidant generation by itself seems neutral with respect to aneurysm progression in MFS; however, lipoic acid-mediated reduction of inhomogeneous regions may potentially associate with less anisotropy and reduced chance of dissection/rupture.

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Section: Methodsmentioning

confidence: 99%

Effect of the Antioxidant Lipoic Acid in Aortic Phenotype in a Marfan Syndrome Mouse Model

Guido

Debbas

Salemi

et al. 2018

Oxidative Medicine and Cellular Longevity

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“…α-Lipoic acid (ALA) is made in the human body and is essential for aerobic metabolism and as a cofactor in several enzymatic reactions. There are no human studies of the effect of ALA on CV calcification but in mice with calcification from heart tissue injury, ALA lowered tissue damage and reduced calcification [ 146 ], while in rabbits it reduced aortic valve and medial calcification [ 121 , 147 ]. N -acetylcysteine (NAC) functions principally as a mucolytic agent and helps to increase endogenous glutathione levels.…”

Section: Antioxidantsmentioning

confidence: 99%

A Review of the Effect of Diet on Cardiovascular Calcification

Nicoll

Howard²,

Henein

2015

IJMS

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Cardiovascular (CV) calcification is known as sub-clinical atherosclerosis and is recognised as a predictor of CV events and mortality. As yet there is no treatment for CV calcification and conventional CV risk factors are not consistently correlated, leaving clinicians uncertain as to optimum management for these patients. For this reason, a review of studies investigating diet and serum levels of macro- and micronutrients was carried out. Although there were few human studies of macronutrients, nevertheless transfats and simple sugars should be avoided, while long chain ω-3 fats from oily fish may be protective. Among the micronutrients, an intake of 800 μg/day calcium was beneficial in those without renal disease or hyperparathyroidism, while inorganic phosphorus from food preservatives and colas may induce calcification. A high intake of magnesium (≥380 mg/day) and phylloquinone (500 μg/day) proved protective, as did a serum 25(OH)D concentration of ≥75 nmol/L. Although oxidative damage appears to be a cause of CV calcification, the antioxidant vitamins proved to be largely ineffective, while supplementation of α-tocopherol may induce calcification. Nevertheless other antioxidant compounds (epigallocatechin gallate from green tea and resveratrol from red wine) were protective. Finally, a homocysteine concentration >12 µmol/L was predictive of CV calcification, although a plasma folate concentration of >39.4 nmol/L could both lower homocysteine and protect against calcification. In terms of a dietary programme, these recommendations indicate avoiding sugar and the transfats and preservatives found in processed foods and drinks and adopting a diet high in oily fish and vegetables. The micronutrients magnesium and vitamin K may be worthy of further investigation as a treatment option for CV calcification.

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“…We identified five types of potential antioxidants with therapeutic effects against VC based on the literature search, including linalool 61 , lipoic acid 22–24 , rosmarinic acid 63 , fermentation broth extracts from Actinobacteria 59 , and polysaccharide from Fuzi product 60 . Two (40%) of them have ROS scavenging ability, while the other three (60%) do not (Fig.…”

Section: Antioxidants From Natural Non-dietary Sourcesmentioning

confidence: 99%

“…Several groups have proposed that lipoic acid could substantially attenuate VC in vitro and in vivo. Liberman et al showed that lipoic acid ameliorated aortic calcification and improved vascular compliance in high cholesterol- and vitamin D-fed rabbits by inhibiting Nox4 expression and reducing ROS 22,24 . Similar to quercetin, lipoic acid exhibited a beneficial effect against VC by improving mitochondrial function and inhibiting apoptosis, through restoring Gas6/Axl survival signaling 23 .…”

Section: Antioxidants From Natural Non-dietary Sourcesmentioning

confidence: 99%

“…Yamada et al showed that tempol could reverse the osteoblastic transdifferentiation of VSMCs and improve uremic VC in CKD rats through ROS reduction and Nox4 inhibition 40 . However, Liberman et al showed that in a rabbit model of atherosclerotic calcification, although tempol lowered aortic ROS levels, it paradoxically increased medial calcification and plaque burden 24 . This can be attributed to the species-dependent or calcification model-dependent actions of tempol, but further studies are needed before arriving at a definite conclusion.…”

Section: Antioxidants With Contradictory Findings Regarding Vcmentioning

confidence: 99%

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Natural and non-natural antioxidative compounds: potential candidates for treatment of vascular calcification

et al. 2019

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Vascular calcification (VC) is highly prevalent in patients with advanced age, or those with chronic kidney disease and diabetes, accounting for substantial global cardiovascular burden. The pathophysiology of VC involves active mineral deposition by transdifferentiated vascular smooth muscle cells exhibiting osteoblast-like behavior, building upon cores with or without apoptotic bodies. Oxidative stress drives the progression of the cellular phenotypic switch and calcium deposition in the vascular wall. In this review, we discuss potential compounds that shield these cells from the detrimental influences of reactive oxygen species as promising treatment options for VC. A comprehensive summary of the current literature regarding antioxidants for VC is important, as no effective therapy is currently available for this disease. We systematically searched through the existing literature to identify original articles investigating traditional antioxidants and novel compounds with antioxidant properties with regard to their effectiveness against VC in experimental or clinical settings. We uncovered 36 compounds with antioxidant properties against VC pathology, involving mechanisms such as suppression of NADPH oxidase, BMP-2, and Wnt/β-catenin; anti-inflammation; and activation of Nrf2 pathways. Only two compounds have been tested clinically. These findings suggest that a considerable opportunity exists to harness these antioxidants for therapeutic use for VC. In order to achieve this goal, more translational studies are needed.

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Lipoic acid, but not tempol, preserves vascular compliance and decreases medial calcification in a model of elastocalcinosis

Cited by 6 publications

References 30 publications

Effect of the Antioxidant Lipoic Acid in Aortic Phenotype in a Marfan Syndrome Mouse Model

Effect of the Antioxidant Lipoic Acid in Aortic Phenotype in a Marfan Syndrome Mouse Model

A Review of the Effect of Diet on Cardiovascular Calcification

Natural and non-natural antioxidative compounds: potential candidates for treatment of vascular calcification

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