Emerging role of various signaling pathways in the pathogenesis and therapeutics of atherosclerosis

Prashar, Yash; Ritu,; Bais, Souravh; Gill, Naresh Singh

doi:10.1016/j.rvm.2017.05.001

Cited by 17 publications

(11 citation statements)

References 156 publications

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“…Immune and inflammatory signals, environmental factors, biochemical pathways, receptors, and enzymes as well as genetic have key roles in initiation, progression, and development of atherosclerosis. (Prashar, Ritu, & Gill, ).…”

Section: Introductionmentioning

confidence: 99%

Bisphenol A vascular toxicity: Protective effect of Vitis vinifera (grape) seed extract and resveratrol

Rameshrad

Imenshahidi

Razavi

et al. 2018

Phytotherapy Research

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The underlying mechanism of Bisphenol A (BPA)-induced vascular toxicity and the protective role of grape seed extract (GSE) and resveratrol were investigated in vitro and in vivo. Human umbilical vein endothelial cells (HUVECs) were exposed to different concentrations of GSE and resveratrol. Then, BPA was added to the cells and cell viability and effects on the protein level of cell adhesion molecules were measured through MTT and western blotting. Animals were randomly divided into control, GSE (3 and 12 mg·kg ·day ip), resveratrol (100 mg·kg ·day ip), BPA (35 mg·kg ·day , gavage), BPA plus GSE (3, 6, and 12 mg·kg ·day ip), BPA plus resveratrol (25, 50, and 100 mg·kg ·day ip), and BPA plus vitamin E (200 IU/kg per every other day ip). After 2 months, contractile and relaxant responses were evaluated on the isolated aorta. BPA increased the level of aorta malondialdehyde (p < 0.001) and decreased vascular responses to KCl (p < 0.01), phenylephrine (p < 0.001), and acetylcholine (p < 0.01). In HUVECs, BPA (IC : 220 μM) increased protein level of vascular cell adhesion molecule (p < 0.05) and cleaved capase3 (p < 0.001). GSE, resveratrol, and vitamin E cotreatment restored toxic effects of BPA in some levels. BPA vascular toxicity was attributed to lipid peroxidation and endothelial dysfunction. The protective role of GSE and resveratrol against BPA-endothelial dysfunction could be attributed to their potent antioxidant properties.

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Section: Introductionmentioning

confidence: 99%

Bisphenol A vascular toxicity: Protective effect of Vitis vinifera (grape) seed extract and resveratrol

Rameshrad

Imenshahidi

Razavi

et al. 2018

Phytotherapy Research

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“…4 A combination of cholesterol clefts and cell disappearance was interpreted as showing the origin of the atherosclerotic core. 5 Advancements in pharmacotherapy are limited to a few targeted factors, which stimulate the release of lipoproteins.…”

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confidence: 99%

Isolation of Prunin FromBauhinia variegataand Its Antioxidant Activity in Rats Fed an Atherogenic Diet

Zhang

2020

Natural Product Communications

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Atherosclerosis is no longer a disease attributed mainly to high cholesterol content in the body; it has come to be regarded as a chronic inflammatory disease with an autoimmune component. The purpose of this study was to investigate the effect of the prunin fraction (PF) isolated from the ethanolic extract of Bauhinia variegata against the release of various proinflammatory mediators in rats fed an atherogenic diet. The diet was administered orally to Sprague Dawley rats for 60 days to induce atherosclerosis. The blood serum of the rats was used to estimate the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), thiobarbituric acid reactive substance, catalase, total cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein using assay kits. Other physical parameters, such as body weight, feed intake, and systolic blood pressure, were also determined during the study. The results showed a significant protective effect of the PF against diet-induced atherosclerosis by decreasing the levels of proinflammatory mediators such as TNF-α and IL-6. Rats treated with PF (20 and 40 mg/kg) showed a change in systolic blood pressure and a reduction in oxidative stress induced by the atherogenic diet. Reduction in body weight and modulation of food intake were observed in PF-treated rats, which indicated atheroprotective, hypolipidemic, and antioxidant effects. The study concludes that the atheroprotective properties of PF are due to effects on the initial phase of plaque formation to thrombus formation. This study may help researchers to find a better alternative for selecting optimal therapies and preventing plaque formation. Future Significance: This article focuses on the molecular mechanisms involved in the evolution of atherosclerotic plaques and different targets that act at the starting stage of the plaque to thrombus formation. This may pave the way for selecting optimal therapies and preventing plaque complications.

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“…Fourteen target genes were involved in cilium assembly, including IFT74, a component of endothelial intraflagellar transport 19 , which interacts with a CVD associated variant in the chr9p21 region (rs944797). It has been shown that endothelial cells can sense and respond to shear stress levels using their cilia 19,20 and endothelial cilia were shown to deflect in response to blood flow rates. The deflection angle is regulated by calcium levels 21 .…”

Section: Gene Enrichment Analysis Of Target Genes Of Gwas Variants Fomentioning

confidence: 99%

“…Although it is established that the risk allele is associated with formation and progression of plaques but not with their rupture 14,15 , the mechanistic understanding of the conferred risk by these loci remains elusive [16][17][18] . Pathways such as cholesterol and triglyceride metabolism, blood pressure, inflammation, vascular proliferation and remodeling, nitric oxide signaling, vascular tone, extracellular matrix integrity and axon guidance and signaling are also enriched for target genes of GWAS variants [17][18][19][20] . GWAS studies do not in themselves provide functional insight for the large subset of hits that are non-coding 21,22 : only one-third of the time a variant affects the expression level of its nearest gene, highlighting the limitations of the nearestgene assignment approach 23,24 .…”

Section: Introductionmentioning

confidence: 99%

High-resolution regulatory maps connect cardiovascular risk variants to disease related pathways

Åkerborg

Spalinskas

Pradhananga

et al. 2018

Preprint

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Genetic variant landscape of cardiovascular disease (CVD) is dominated by noncoding variants among which many occur within putative enhancers regulating the expression levels of relevant genes. It is crucial to assign the genetic variants to their correct gene both to gain insights into perturbed functions and better assess the risk of disease. In this study, we generated high-resolution genomic interaction maps (~750 bases) in aortic endothelial, smooth muscle and THP-1 macrophages using Hi-C coupled with sequence capture targeting 25,429 features including variants associated with CVD. We detected interactions for 761 CVD risk variants obtained by genome-wide association studies (GWAS) and identified novel as well as established functions associated with CVD. We were able to finemap 331 GWAS variants using interaction networks, thereby identifying additional genes and functions. We also discovered a subset of risk variants interacting with multiple promoters and the expression levels of such genes were correlated. The presented resource enables functional studies of cardiovascular disease providing novel approaches for its diagnosis and treatment.

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Emerging role of various signaling pathways in the pathogenesis and therapeutics of atherosclerosis

Cited by 17 publications

References 156 publications

Bisphenol A vascular toxicity: Protective effect of Vitis vinifera (grape) seed extract and resveratrol

Bisphenol A vascular toxicity: Protective effect of Vitis vinifera (grape) seed extract and resveratrol

Isolation of Prunin FromBauhinia variegataand Its Antioxidant Activity in Rats Fed an Atherogenic Diet

High-resolution regulatory maps connect cardiovascular risk variants to disease related pathways

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