Expression of chemokines in macrophage polarization and downregulation of NFκB in aorta allow macrophage polarization by diosgenin in atherosclerosis

Binesh, Ambika; Devaraj, S. Niranjali; Devaraj, Halagowder

doi:10.1002/jbt.22422

Cited by 20 publications

(12 citation statements)

References 19 publications

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“…As reported by Binesh et al [ 84 ], notch intracellular domain (NICD) could be regulated by NF- κ B inhibition, which in turn down macrophage differentiation afterward. He further proved [ 85 ] that diosgenin regulates the differentiation of monocyte not by inhibiting its differentiation to macrophage but inducing its differentiation to M2 macrophage, thus, preventing the promotion of atherosclerosis. In addition, HIF [ 79 ] is reported as a crucial factor which could mediate the formation of foam cells by regulating efflux pathways in macrophages through the NF- κ B signaling pathway.…”

Section: Cytokines/receptors and Other Biochemical Factors Involved In Monocyte Migrationmentioning

confidence: 99%

“…Earlier studies demonstrated that oxidized LDL (oxLDL) could promote the differentiation of monocyte [ 84 , 85 ], the chemotaxis of macrophages [ 87 ], but inhibit their egress [ 88 , 89 ]. Recent studies showed that oxLDL mainly induces monocytes differentiated to M1 macrophage, which are proinflammatory [ 90 ] and assumed to have lower migration ability [ 91 ].…”

Section: Cytokines/receptors and Other Biochemical Factors Involved In Monocyte Migrationmentioning

confidence: 99%

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The Entry and Egress of Monocytes in Atherosclerosis: A Biochemical and Biomechanical Driven Process

Xiong

et al. 2021

Cardiovascular Therapeutics

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In accordance with “the response to injury” theory, the entry of monocytes into the intima guided by inflammation signals, taking up cholesterol and transforming into foam cells, and egress from plaques determines the progression of atherosclerosis. Multiple cytokines and receptors have been reported to be involved in monocyte recruitment such as CCL2/CCR2, CCL5/CCR5, and CX3CL1/CX3CR1, and the egress of macrophages from the plaque like CCR7/CCL19/CCL21. Interestingly, some neural guidance molecules such as Netrin-1 and Semaphorin 3E have been demonstrated to show an inhibitory effect on monocyte migration. During the processes of monocytes recruitment and migration, factors affecting the biomechanical properties (e.g., the membrane fluidity, the deformability, and stiffness) of the monocytes, like cholesterol, amyloid-β peptide (Aβ), and lipopolysaccharides (LPS), as well as the biomechanical environment that the monocytes are exposed, like the extracellular matrix stiffness, mechanical stretch, blood flow, and hypertension, were discussed in the latter section. Till now, several small interfering RNAs (siRNAs), monoclonal antibodies, and antagonists for CCR2 have been designed and shown promising efficiency on atherosclerosis therapy. Seeking more possible biochemical factors that are chemotactic or can affect the biomechanical properties of monocytes, and uncovering the underlying mechanism, will be helpful in future studies.

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Section: Cytokines/receptors and Other Biochemical Factors Involved In Monocyte Migrationmentioning

confidence: 99%

Section: Cytokines/receptors and Other Biochemical Factors Involved In Monocyte Migrationmentioning

confidence: 99%

The Entry and Egress of Monocytes in Atherosclerosis: A Biochemical and Biomechanical Driven Process

Xiong

et al. 2021

Cardiovascular Therapeutics

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“…Macrophages are mainly divided into two different subtypes: M1-type macrophages are mainly found in unstable plaques, whereas M2-type macrophages are predominantly found in stable plaque tissue (5,6). During the development of the disease, various external factors affect macrophages, and depending on the M1/M2 polarization status, the corresponding inflammatory process is highly different (5,7). Binesh et al (7) found that pro-inflammatory macrophages (M1-type) were expressed in atherogenic diet-induced aorta, while anti-inflammatory macrophages (M2-type) were expressed in diosgenin-treated aorta.…”

Section: Introductionmentioning

confidence: 99%

“…During the development of the disease, various external factors affect macrophages, and depending on the M1/M2 polarization status, the corresponding inflammatory process is highly different (5,7). Binesh et al (7) found that pro-inflammatory macrophages (M1-type) were expressed in atherogenic diet-induced aorta, while anti-inflammatory macrophages (M2-type) were expressed in diosgenin-treated aorta. Therefore, improving the condition of the disease by regulating the polarization of M1-type macrophages may be one mechanism to control immune regulation in atherosclerosis.…”

Section: Introductionmentioning

confidence: 99%

Angiotensin II induces RAW264.7 macrophage polarization to the M1‑type through the connexin 43/NF‑κB pathway

Chen

Xiao

et al. 2020

Mol Med Report

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angiotensin ii (angii) serves an important inflammatory role in cardiovascular disease; it can induce macrophages to differentiate into the M1-type, produce inflammatory cytokines and resist pathogen invasion, and can cause a certain degree of damage to the body. Previous studies have reported that connexin 43 (Cx43) and NF-κB (p65) are involved in the AngII-induced inflammatory pathways of macrophages; however, the mechanisms underlying the effects of Cx43 and NF-κB (p65) on AngII-induced macrophage polarization have not been determined. Thus, the present study aimed to investigate the effects of Cx43 and NF-κB (p65) on the polarization process of AngII-induced macrophages. The macrophage polarization-related proteins and mRNAs were examined by flow cytometry, western blotting, immunofluorescence, ELISA and reverse transcription-quantitative PCR analyses. RAW264.7 macrophages were treated with AngII to simulate chronic inflammation and it was subsequently found that AngII promoted RAW 264.7 macrophage polarization towards the M1-type by such effects as the release of inducible nitric oxide synthase (iNOS), tumour necrosis factor (TNF)-α, il-1β, the secretion of IL-6, and the expression of M1-type indicators, such as CD86. Simultaneously, compared with the control group, the protein expression levels of Cx43 and phosphorylated (p)-p65 were significantly increased following AngII treatment. The M1-related phenotypic indicators, iNOS, TNF-α, il-1β, IL-6 and CD86, were inhibited by the NF-κB (p65) signalling pathway inhibitor BAY117082. Similarly, the Cx43 inhibitors, Gap26 and Gap19, also inhibited the expression of M1-related factors, and the protein expression levels of p-p65 in the Gap26/Gap19 groups were significantly decreased compared with the AngII group. Altogether, these findings suggested that AngII may induce the polarization of RAW264.7 macrophages to the M1-type through the Cx43/NF-κB (p65) signalling pathway.

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“…CVD claims more lives than all forms of cancer deaths combined. Cardiovascular diseases are the first leading cause of death and morbidity in developed countries (Gaziano et al 2010;Binesh et al 2020a;Binesh et al 2020b). The use of animal models has helped to increase our understanding, opening up new tools that are concentrated on strengthening the diagnosis and treatment of these pathologies.…”

Section: Introductionmentioning

confidence: 99%

Decades‐long involvement of signalling pathways in cardiovascular research using zebrafish model and its global trends

Binesh

2020

Reviews in Aquaculture

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Research on zebrafish as a model system began a few decades ago, and later, studies on zebrafish developmental biology and genetics resulted in the characterization of a large number of genes involved in vertebrate development and cell signalling pathways, thus establishing zebrafish as a relevant human disease model for research. Cardiovascular diseases (CVDs) are the first leading cause of death and are expected to rise over 23.6 million by 2030. Environmental toxicants such as drugs, alcohols and chemicals can activate/disrupt number of signalling pathways, led to the cardiovascular toxicity and perturb the development of myocardium, cardiomyocytes, cardiac valve formation and cardiac trabecular growth. Based on the total publication output, USA's contribution to cardiovascular research using zebrafish as a model organism was immense compared to that of other countries. Harvard University contributed comprehensive research on CVD using zebrafish model with a cumulative occurrence of keywords like zebrafish, angiogenesis, cardiovascular disease, pollutants and developmental process. Many pathways are redundant, and the activation of certain targets implicated in cardiovascular disease development is by inhibiting one particular pathway leading to activation of alternative signalling pathways. Targeting highly specific pathways by single compounds inhibiting only one protein generally leads to resistance to this therapeutic agent. It is understood from the publications and citations, that the use of zebrafish as a cardiovascular disease (CVD) model has been gradually expanded from 2000 to 2019, likely due to the recapitulated pathophysiology of the human heart.

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Expression of chemokines in macrophage polarization and downregulation of NFκB in aorta allow macrophage polarization by diosgenin in atherosclerosis

Cited by 20 publications

References 19 publications

The Entry and Egress of Monocytes in Atherosclerosis: A Biochemical and Biomechanical Driven Process

The Entry and Egress of Monocytes in Atherosclerosis: A Biochemical and Biomechanical Driven Process

Angiotensin II induces RAW264.7 macrophage polarization to the M1‑type through the connexin 43/NF‑κB pathway

Decades‐long involvement of signalling pathways in cardiovascular research using zebrafish model and its global trends

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