Macrophage lipid accumulation in the presence of immunosuppressive drugs mycophenolate mofetil and cyclosporin A

Voloshyna, Iryna; Teboul, Isaac; Kasselman, Lora J.; Salama, Michael; Carsons, Steven E.; DeLeon, Joshua; Mattana, Joseph; Miyawaki, Nobuyuki; Reiss, Allison B.

doi:10.1007/s00011-019-01262-8

Cited by 11 publications

(9 citation statements)

References 54 publications

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“…Collectively, metabolic regulation of macrophages in lupus erythematosus patients can alleviate disease progression and provide some protection against kidney damage [ 109 , 110 ]. This study provides a new direction for the treatment of LN.…”

Section: Macrophages In Autoimmune Disease Kidney Damage and Repairmentioning

confidence: 99%

Reprogramming Metabolism of Macrophages as a Target for Kidney Dysfunction Treatment in Autoimmune Diseases

Tian

Chen

Zhang

et al. 2022

IJMS

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Chronic kidney disease (CKD), as one of the main complications of many autoimmune diseases, is difficult to cure, which places a huge burden on patients’ health and the economy and poses a great threat to human health. At present, the mainstream view is that autoimmune diseases are a series of diseases and complications caused by immune cell dysfunction leading to the attack of an organism’s tissues by its immune cells. The kidney is the organ most seriously affected by autoimmune diseases as it has a very close relationship with immune cells. With the development of an in-depth understanding of cell metabolism in recent years, an increasing number of scientists have discovered the metabolic changes in immune cells in the process of disease development, and we have a clearer understanding of the characteristics of the metabolic changes in immune cells. This suggests that the regulation of immune cell metabolism provides a new direction for the treatment and prevention of kidney damage caused by autoimmune diseases. Macrophages are important immune cells and are a double-edged sword in the repair process of kidney injury. Although they can repair damaged kidney tissue, over-repair will also lead to the loss of renal structural reconstruction function. In this review, from the perspective of metabolism, the metabolic characteristics of macrophages in the process of renal injury induced by autoimmune diseases are described, and the metabolites that can regulate the function of macrophages are summarized. We believe that treating macrophage metabolism as a target can provide new ideas for the treatment of the renal injury caused by autoimmune diseases.

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Section: Macrophages In Autoimmune Disease Kidney Damage and Repairmentioning

confidence: 99%

Reprogramming Metabolism of Macrophages as a Target for Kidney Dysfunction Treatment in Autoimmune Diseases

Tian

Chen

Zhang

et al. 2022

IJMS

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“…Cyclosporine A has been found to reduce carotid intima-media thickness in SLE patients [184,185]. However, cyclosporine A is a known competitive inhibitor of the reverse cholesterol transport protein 27-hydroxylase and so its effect on cholesterol processing and disposition is unpredictable [186].…”

Section: Novel Therapeuticsmentioning

confidence: 99%

Understanding Accelerated Atherosclerosis in Systemic Lupus Erythematosus: Toward Better Treatment and Prevention

et al. 2021

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Systemic lupus erythematosus (SLE) carries a significant risk of cardiovascular disease (CVD). The prevalence of premature CVD is especially noteworthy because it occurs in premenopausal women with SLE who would otherwise have very low rates of CVD. While traditional risk factors likely play a role in development of CVD in the setting of SLE, they do not fully explain the excess risk. The pathogenesis of CVD in SLE is not fully understood, but the inflammatory nature of SLE is believed to be a key factor in accelerating atherosclerosis. Systemic inflammation may lead to an abnormal lipid profile with elevated triglycerides, total cholesterol, and low-density lipoprotein cholesterol and dysfunctional high-density lipoprotein cholesterol. Additionally, the inflammatory milieu of SLE plasma promotes endothelial dysfunction and vascular injury, early steps in the progression of atherosclerotic CVD. Despite the overall headway that has been achieved in treating lupus, innovative therapeutics specifically targeting the progression of atherosclerosis within the lupus population are currently lacking. However, there have been advancements in the development of promising modalities for diagnosis of subclinical atherosclerosis and detection of high CVD risk patients. Due to the significant impact of CVD on morbidity and mortality, research addressing prevention and treatment of CVD in SLE needs to be prioritized. This review explores the intricate interplay of SLE-specific properties that contribute to atherosclerosis and CVD within this population, as well as screening methods and possible therapies.

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“…Herein, we employed an HFD‐fed ApoE −/− mouse model to explore therapeutic strategies against CsA‐induced atherosclerosis, as done in several studies exploring the effects of CsA in ApoE −/− mice (Matsumoto et al, 2003; Moghadasian, 2006; Voloshyna et al, 2019). ApoE −/− mice spontaneously and rapidly develop atherosclerosis and hypercholesterolemia.…”

Section: Discussionmentioning

confidence: 99%

Dual action of macrophage miR‐204 confines cyclosporine A‐induced atherosclerosis

Su,

Hong,

Han

et al. 2023

British J Pharmacology

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Background and PurposeAtherosclerosis induced by cyclosporine A (CsA), an inhibitor of the calcineurin/nuclear factor of activated T cells (NFAT) pathway, is a major concern after organ transplantation. However, the atherosclerotic mechanisms of CsA remain obscure. We previously demonstrated that calcineurin/NFAT signalling inhibition contributes to atherogenesis via suppressing microRNA‐204 (miR‐204) transcription. We therefore hypothesised that miR‐204 is involved in the development of CsA‐induced atherosclerosis.Experimental ApproachApoE−/− mice with macrophage‐miR‐204 overexpression were generated to determine the effects of miR‐204 on CsA‐induced atherosclerosis. Luciferase reporter assays and chromatin immunoprecipitation sequencing were performed to explore the targets mediating miR‐204 effects.Key ResultsCsA alone did not significantly affect atherosclerotic lesions or serum lipid levels. However, it exacerbated high‐fat diet‐induced atherosclerosis and hyperlipidemia in C57BL/6J and ApoE−/− mice, respectively. miR‐204 levels decreased in circulating monocytes and plaque lesions during CsA‐induced atherosclerosis. The upregulation of miR‐204 in macrophages inhibited CsA‐induced atherosclerotic plaque formation but did not affect serum lipid levels. miR‐204 limited the CsA‐induced foam cell formation by reducing the expression of the scavenger receptors SR‐BII and CD36. SR‐BII was post‐transcriptionally regulated by mature miR‐204‐5p via 3′‐UTR targeting. Additionally, nuclear‐localised miR‐204‐3p prevented the CsA‐induced binding of Ago2 to the CD36 promoter, suppressing CD36 transcription. SR‐BII or CD36 expression restoration dampened the beneficial effects of miR‐204 on CsA‐induced atherosclerosis.Conclusion and ImplicationsMacrophage miR‐204 ameliorates CsA‐induced atherosclerosis, suggesting that miR‐204 may be a potential target for the prevention and treatment of CsA‐related atherosclerotic side effects.

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Macrophage lipid accumulation in the presence of immunosuppressive drugs mycophenolate mofetil and cyclosporin A

Cited by 11 publications

References 54 publications

Reprogramming Metabolism of Macrophages as a Target for Kidney Dysfunction Treatment in Autoimmune Diseases

Reprogramming Metabolism of Macrophages as a Target for Kidney Dysfunction Treatment in Autoimmune Diseases

Understanding Accelerated Atherosclerosis in Systemic Lupus Erythematosus: Toward Better Treatment and Prevention

Dual action of macrophage miR‐204 confines cyclosporine A‐induced atherosclerosis

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