Atorvastatin Inhibits CD68 Expression in Aortic Root Through a GRP78-Involved Pathway

Li, Ling; Wang, Yu; Xu, Yuanfu; Chen, Lianfeng; Fang, Quan; Yan, Xiaowei

doi:10.1007/s10557-014-6556-3

Cited by 12 publications

(7 citation statements)

References 34 publications

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“…It is important to mention that a possible limitation of this study are the potential interactions, synergisms, or detriments that may arise when studying or implementing novel drugs like SS-31 in a background affected by other medications such as statins. In this sense, previous research has stated that statins can have both detrimental [63,64,65,66] and beneficial effects [67,68,69,70,71,72,73,74,75,76,77], often unrelated to their lipid-lowering effect and rather associated with their pleiotropic actions. The variation of the effect is explained by the type of statin, the dose, the combination with other treatments and the experimental model.…”

Section: Discussionmentioning

confidence: 99%

The Mitochondrial Antioxidant SS-31 Modulates Oxidative Stress, Endoplasmic Reticulum Stress, and Autophagy in Type 2 Diabetes

Escribano-López

Iannantuoni

López‐Domènech

et al. 2019

JCM

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Mitochondrial dysfunction has been shown to play a central role in the pathophysiology of type 2 diabetes (T2D), and mitochondria-targeted agents such as SS-31 are emerging as a promising strategy for its treatment. We aimed to study the effects of SS-31 on leukocytes from T2D patients by evaluating oxidative stress, endoplasmic reticulum (ER) stress and autophagy. Sixty-one T2D patients and 53 controls were included. Anthropometric and analytical measurements were performed. We also assessed reactive oxygen species (ROS) production, calcium content, the expression of ER stress markers GRP78, CHOP, P-eIF2α, and autophagy-related proteins Beclin1, LC3 II/I, and p62 in leukocytes from T2D and control subjects treated or not with SS-31. Furthermore, we have evaluated the action of SS-31 on leukocyte-endothelium interactions. T2D patients exhibited elevated ROS concentration, calcium levels and presence of ER markers (GRP78 and CHOP gene expression, and GRP78 and P-eIF2α protein expression), all of which were reduced by SS-31 treatment. SS-31 also led to a drop in BECN1 gene expression, and Beclin1 and LC3 II/I protein expression in T2D patients. In contrast, the T2D group displayed reduced p62 protein levels that were restored by SS-31. SS-20 (with non-antioxidant activity) did not change any analyzed parameter. In addition, SS-31 decreased rolling flux and leukocyte adhesion, and increased rolling velocity in T2D patients. Our findings suggest that SS-31 exerts potentially beneficial effects on leukocytes of T2D patients modulating oxidative stress and autophagy, and ameliorating ER stress.

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Section: Discussionmentioning

confidence: 99%

The Mitochondrial Antioxidant SS-31 Modulates Oxidative Stress, Endoplasmic Reticulum Stress, and Autophagy in Type 2 Diabetes

Escribano-López

Iannantuoni

López‐Domènech

et al. 2019

JCM

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“…Li et al [36] showed that the increase in the activity of the Lecithin: Cholesterol Acyltransferase Activity (LCAT) and probably the reduction in that of hydroxy-methyl-glutary-coenzyme A reductase (HMG-CoA reductase), both ensuring the homeostasis of cholesterol, could be regarded as persons in charge for the reduction in the cholesterolemy, in the rat subjected to a feeding regime enriched with cholesterol treated with 5% by the extract by Coriandrum sativum during 75 days [36]. Moreover, Sudhop et al [37] noted a rise in the activity of the LCAT and an inhibition of HMG-CoA reductase, in the rat made hypercholesterolemic treated with 500 mg/kg of an extract leaves of Symplocos cochinchinensis , during 28 days [38].…”

Section: Discussionmentioning

confidence: 99%

Hypolipidemic, antioxidant and anti-atherosclerogenic effect of aqueous extract leaves of Cassia. occidentalis Linn (Caesalpiniaceae) in diet-induced hypercholesterolemic rats

Ntchapda

Barama

Talla

et al. 2017

BMC Complement Altern Med

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BackgroundHyperlipidemia and oxidative stress are major risk factors for atherosclerosis, and all three are among the most important risk factors for cardiovascular diseases. Cassia occidentalis aqueous extract has been used in African traditional medicine for the treatment of hypertension and associated cardiovascular diseases. This study was undertaken to evaluate the hypolipidemic and anti-atherosclerotic properties of the aqueous extract of the leaves of C. occidentalis in rats with hypercholesterolemia (HC).Sixty Normocholesterolemic (NC) male rats were divided into six groups (n = 10) and fed a high-cholesterol (HC) diet for 30 days (5 groups), or normal rat chow (normal control group). The plant extract was administered to animals at the increasing dose of 240, 320 and 400 mg/kg. After 4 weeks of treatment 5 rats out of 10 were sacrificed, blood samples, aorta, liver, and fresh faecal were collected and processed for biochemical tests. The experiments were conducted under the same conditions with a group of rat treated with Atorvastatin (1 mg/kg), used positive control. The effects of C. occidentalis on weight gain, water and food consumptions, levels of serum lipids and lipoprotein lipid oxidation and stress markers in blood and liver were also examined.ResultsA significant body weight gain was observed in general in all the group of animals without any treatment after 4 weeks. During the treatment period, the C. occidentalis extract induced a significant increase (P < 0.01) in water consumption and food intakes. After 4 weeks of treatment with hypercholesterolemia, the body temperature and organ weights including the liver, kidney, heart and the testis did not present any significant change. The administration of C. occidentalis extract significantly (p < 0.05) prevented the elevation in TC, LDL-C, VLDL-C, hepatic and aortic TG and TC. The atherogenic, triglycerides, and lipid peroxidation (TBARS) index were also decreased in the rats treated with the plant extract. C. occidentalis favoured the performance of faecal cholesterol. It also significantly inhibited the changes and the formation of aortic atherosclerotic plaques.ConclusionThis study provides evidence of hypolipidemic and antiatherosclerotic effects of C. occidentalis extract. C. occidenntalis aqueous extract reduced bad cholesterols, triglycerides and increasing good cholesterols in rats subjected to a feeding regime enriched with cholesterol. The results support the traditional use of the extract of this plant in the treatment of hypertension and diabetes.

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“…Foam cells are mainly derived from CD68-positive monocytes and macrophages that migrate from the vascular lumen to the wall [ 35 ]. The agents that regulate CD68 expression and macrophage infiltration may determine in the progression or regression of atherosclerosis [ 36 ]. In the present study, we found that the APs and ATO reduced the numbers of CD68-positive cells by 39% and 69%, respectively ( Figure 5 ).…”

Section: Discussionmentioning

confidence: 99%

Apple Polyphenols Decrease Atherosclerosis and Hepatic Steatosis in ApoE−/− Mice through the ROS/MAPK/NF-κB Pathway

Dong

et al. 2015

Nutrients

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In this study, we examined the effects of apple polyphenols (APs) on hyperlipidemia, atherosclerosis, hepatic steatosis and endothelial function and investigated the potential mechanisms. ApoE−/− mice were fed a western-type diet and orally treated with APs (100 mg/kg) or atorvastatin (10 mg/kg) for 12 weeks. Hyperlipidemia and atherosclerosis in the aortic sinuses and, and hepatic lipidosis were measured. The treatment with APs or atorvastatin induced a remarkable reduction in the atherosclerotic lesions and hepatic steatosis and decreased the levels of low-density lipoprotein, triglyceride, CCL-2 and VCAM-1 levels in the plasma. Conversely, the APs significantly increased the plasma levels of high-density lipoprotein (HDL) cholesterol and markedly up-regulated the glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) levels in liver tissues. Moreover, the APs treatment modulated lipid metabolism by up-regulating the transcription of associated hepatic genes including PPARα, while down-regulating the transcription of SCAP and its downstream genes associated with lipid synthesis in the liver. Histological assessment showed that the APs treatment also reduced the macrophage infiltration in the aortic root plaque and the inflammatory cells infiltrations to the liver tissues. Moreover, we confirmed that the APs treatment greatly reduced the ox-LDL-induced endothelial dysfunction and monocyte adhesion to rat aortic endothelial cells (RAECs). Mechanistically, the APs treatment suppressed the ROS/MAPK/NF-κB signaling pathway, and consequently, reduced CCL-2, ICAM-1 and VCAM-1 expression. Our results suggest that the APs are a beneficial nutritional supplement for the attenuation of atherosclerosis.

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Atorvastatin Inhibits CD68 Expression in Aortic Root Through a GRP78-Involved Pathway

Cited by 12 publications

References 34 publications

The Mitochondrial Antioxidant SS-31 Modulates Oxidative Stress, Endoplasmic Reticulum Stress, and Autophagy in Type 2 Diabetes

The Mitochondrial Antioxidant SS-31 Modulates Oxidative Stress, Endoplasmic Reticulum Stress, and Autophagy in Type 2 Diabetes

Hypolipidemic, antioxidant and anti-atherosclerogenic effect of aqueous extract leaves of Cassia. occidentalis Linn (Caesalpiniaceae) in diet-induced hypercholesterolemic rats

Apple Polyphenols Decrease Atherosclerosis and Hepatic Steatosis in ApoE−/− Mice through the ROS/MAPK/NF-κB Pathway

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