Nrf2 deficiency attenuates atherosclerosis by reducing LOX-1-mediated proliferation and migration of vascular smooth muscle cells

Li, Hongliang; Zhuang, Wenwen; Xiong, Tianqing; Park, Won Sun; Zhang, Song; Zha, Yiwen; Yao, Jiali; Wang, Fangfang; Yang, Yongqi; Chen, Yingrui; Cai, Linqian; Ling, Ling; Yu, Duonan; Liang, Jingyan

doi:10.1016/j.atherosclerosis.2022.02.025

Cited by 18 publications

(12 citation statements)

References 51 publications

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“…In line with this notion, several studies found that NRF2 activation attenuated oxidative stress and inflammation in AS. [30][31][32][33][34][35] These studies, along with the present work, demonstrated that NRF2 is a viable target for AS intervention.…”

Section: Discussionsupporting

confidence: 73%

Cardamonin targets KEAP1/NRF2 signaling for protection against atherosclerosis

et al. 2023

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Section: Discussionsupporting

confidence: 73%

Cardamonin targets KEAP1/NRF2 signaling for protection against atherosclerosis

et al. 2023

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“…Downregulation of Nrf2 and HO-1 expression was observed in an earlier mouse model of DOX-induced chronic cardiotoxicity (X. Li et al, 2022 ). More recent studies on cultured rat cardiomyocytes showed that overexpression of Nrf2 ameliorates DOX-induced myocardial oxidative damage, mitochondrial dysfunction and cardiac myocyte death via enhancing anti-oxidative activity (Y.…”

Section: Role Of Nrf2 Signaling In Cvdsmentioning

confidence: 87%

“…Notably, knockdown of Nrf2 abolished the protective effect of AR in these cells (J. Li et al, 2022 ) ( Table 1 ).…”

Section: Protective Effects Of Natural Products On Cvdsmentioning

confidence: 95%

Activation of Nrf2 signaling: A key molecular mechanism of protection against cardiovascular diseases by natural products

Wei

Yang

et al. 2022

Front. Pharmacol.

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Cardiovascular diseases (CVD) are a group of cardiac and vascular disorders including myocardial ischemia, congenital heart disease, heart failure, hypertension, atherosclerosis, peripheral artery disease, rheumatic heart disease, and cardiomyopathies. Despite considerable progress in prophylaxis and treatment options, CVDs remain a leading cause of morbidity and mortality and impose an extremely high socioeconomic burden. Oxidative stress (OS) caused by disequilibrium in the generation of reactive oxygen species plays a crucial role in the pathophysiology of CVDs. Nuclear erythroid 2-related factor 2 (Nrf2), a transcription factor of endogenous antioxidant defense systems against OS, is considered an ideal therapeutic target for management of CVDs. Increasingly, natural products have emerged as a potential source of Nrf2 activators with cardioprotective properties and may therefore provide a novel therapeutic tool for CVD. Here, we present an updated comprehensive summary of naturally occurring products with cardioprotective properties that exert their effects by suppression of OS through activation of Nrf2 signaling, with the aim of providing useful insights for the development of therapeutic strategies exploiting natural products.

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“…Further, small molecule niclosamide, a known signal transducers and activators of transcription 3 (STAT3) inhibitor reduces LOX-1 expression in vivo and in vitro on VSMCs [32 ▪ ]. oxLDL receptors induce proliferation of VSMCs as shown by nuclear factor erythroid 2-related factor 2 (Nrf2) deficiency, attenuating atherosclerosis by reducing LOX-1-mediated proliferation and migration of VSMCs in ApoE -/- mice [33]. Also, CD36 deletion attenuates VSMC proliferation and significantly reduces injury-induced neointimal thickening (neointimal hyperplasia) in ApoE -/- mice [34].…”

Section: Role Of Oxldl Receptors In Cellular Dysfunctionmentioning

confidence: 99%

Oxidized LDL receptors: a recent update

Khan

Mohammad

Banerjee

et al. 2023

Current Opinion in Lipidology

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Purpose of review LDL in its oxidized form, or ‘oxLDL’, is now generally acknowledged to be highly proatherogenic and to play a significant role in atherosclerotic plaque formation. Therefore, there has been increasing interest in understanding the significance of oxLDL and its receptors in different phases of atherosclerosis, leading to the accumulation of additional data at the cellular, structural, and physiological levels. This review focuses on the most recent discoveries about these receptors and how they influence lipid absorption, metabolism, and inflammation in various cell types. Recent findings Two crystal structures of lectin-like oxLDL receptor-1 (LOX-1), one with a small molecule inhibitor and the other with a monoclonal antibody have been published. We recently demonstrated that the ‘surface site’ of LOX1, adjacent to the positively charged ‘basic spine region’ that facilitates oxLDL binding, is a targetable site for drug development. Further, recent human studies showed that soluble LOX-1 holds potential as a biomarker for cardiovascular disease diagnosis, prognosis, and assessing the efficacy of therapy. Summary Receptor-mediated oxLDL uptake results in cellular dysfunction of various cell types involved in atherogenesis and plaque development. The current advancements clearly demonstrate that targeting oxLDL-LOX-1 axis may lead to development of future therapeutics for the treatment of atherosclerotic cardiovascular and cerebrovascular diseases.

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Nrf2 deficiency attenuates atherosclerosis by reducing LOX-1-mediated proliferation and migration of vascular smooth muscle cells

Cited by 18 publications

References 51 publications

Cardamonin targets KEAP1/NRF2 signaling for protection against atherosclerosis

Cardamonin targets KEAP1/NRF2 signaling for protection against atherosclerosis

Activation of Nrf2 signaling: A key molecular mechanism of protection against cardiovascular diseases by natural products

Oxidized LDL receptors: a recent update

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