<scp>FURIN</scp> suppresses the progression of atherosclerosis by promoting macrophage autophagy

Chen, Zhidong; Zhang, Lihui; Mi, Shao-Hua; Wang, Hua; Wang, Chunxiao; Jia, Wenjuan; Gong, Lei; Dong, Haibin; Xu, Bowen; Jing, Yanyan; Ge, Peipei; Pei, Zhigang; Zhong, Lin; Jun, Yang

doi:10.1096/fj.202201762rr

Cited by 7 publications

(9 citation statements)

References 48 publications

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“…121 In addition, aortic tissues from five patients who underwent the Bentall procedure showed increased furin levels and autophagic markers in the plaque. 121 Whether this controversial observation is a result of sex difference requires further research.…”

Section: ■ Atherosclerosismentioning

confidence: 96%

“…In contrast, furin overexpression promotes neointimal plaque formation in Apoe –/– mice with a wire injury model of atherosclerosis (Table ), supporting the role of furin in promoting atherosclerotic plaque progression in vivo (Figure ). However, the role of furin in vivo has been complicated by a recent study demonstrating that an increase in furin might suppress the progression of atherosclerosis . Female Apoe –/– mice fed a high-fat diet and with furin overexpression have enhanced macrophage autophagy, attenuated growth of intra-aortic plaques, and reduced plaque vulnerability .…”

Section: Atherosclerosismentioning

confidence: 99%

“…However, the role of furin in vivo has been complicated by a recent study demonstrating that an increase in furin might suppress the progression of atherosclerosis . Female Apoe –/– mice fed a high-fat diet and with furin overexpression have enhanced macrophage autophagy, attenuated growth of intra-aortic plaques, and reduced plaque vulnerability . In addition, aortic tissues from five patients who underwent the Bentall procedure showed increased furin levels and autophagic markers in the plaque .…”

Section: Atherosclerosismentioning

confidence: 99%

“…121 Female Apoe −/− mice fed a high-fat diet and with furin overexpression have enhanced macrophage autophagy, attenuated growth of intraaortic plaques, and reduced plaque vulnerability. 121 In addition, aortic tissues from five patients who underwent the Bentall procedure showed increased furin levels and autophagic markers in the plaque. 121 Whether this controversial observation is a result of sex difference requires further research.…”

Section: ■ Atherosclerosismentioning

confidence: 99%

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Functional Roles of Furin in Cardio-Cerebrovascular Diseases

Wichaiyo,

Koonyosying,

Morales

2024

ACS Pharmacol. Transl. Sci.

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Furin plays a major role in post-translational modification of several biomolecules, including endogenous hormones, growth factors, and cytokines. Recent reports have demonstrated the association of furin and cardio-cerebrovascular diseases (CVDs) in humans. This review describes the possible pathogenic contribution of furin and its substrates in CVDs. Early-stage hypertension and diabetes mellitus show a negative correlation with furin. A reduction in furin might promote hypertension by decreasing maturation of B-type natriuretic peptide (BNP) or by decreasing shedding of membrane (pro)renin receptor (PRR), which facilitates activation of the renin−angiotensin−aldosterone system (RAAS). In diabetes, furin downregulation potentially leads to insulin resistance by reducing maturation of the insulin receptor. In contrast, the progression of other CVDs is associated with an increase in furin, including dyslipidemia, atherosclerosis, ischemic stroke, myocardial infarction (MI), and heart failure. Upregulation of furin might promote maturation of membrane type 1-matrix metalloproteinase (MT1-MMP), which cleaves low-density lipoprotein receptor (LDLR), contributing to dyslipidemia. In atherosclerosis, elevated levels of furin possibly enhance maturation of several substrates related to inflammation, cell proliferation, and extracellular matrix (ECM) deposition and degradation. Neuronal cell death following ischemic stroke has also been shown to involve furin substrates (e.g., MT1-MMP, hepcidin, and hemojuvelin). Moreover, furin and its substrates, including tumor necrosis factor-α (TNF-α), endothelin-1 (ET-1), and transforming growth factor-β1 (TGF-β1), are capable of mediating inflammation, hypertrophy, and fibrosis in MI and heart failure. Taken together, this evidence provides functional significance of furin in CVDs and might suggest a potential novel therapeutic modality for the management of CVDs.

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Section: ■ Atherosclerosismentioning

confidence: 96%

Section: Atherosclerosismentioning

confidence: 99%

Section: Atherosclerosismentioning

confidence: 99%

Section: ■ Atherosclerosismentioning

confidence: 99%

See 2 more Smart Citations

Functional Roles of Furin in Cardio-Cerebrovascular Diseases

Wichaiyo,

Koonyosying,

Morales

2024

ACS Pharmacol. Transl. Sci.

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“…Apoptotic macrophages are exacerbated by MST1‐mediated autophagy inhibition, which secrete inflammatory factors to deteriorate the death of VSMCs, altogether contributing to plaque vulnerability 155 . Furthermore, FURIN increases VSMC proliferation and lipid droplet translocation to arrest AS by the AMPK‐ULK‐PI3K pathway 156 . Notably, chaperone‐mediated autophagy also takes part in AS development.…”

Section: Significance Of Macrophage Autophagy In Cvdsmentioning

confidence: 99%

Comprehensive view of macrophage autophagy and its application in cardiovascular diseases

Pan,

Zhang,

Zhang

et al. 2023

Cell Proliferation

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Cardiovascular diseases (CVDs) are the primary drivers of the growing public health epidemic and the leading cause of premature mortality and economic burden worldwide. With decades of research, CVDs have been proven to be associated with the dysregulation of the inflammatory response, with macrophages playing imperative roles in influencing the prognosis of CVDs. Autophagy is a conserved pathway that maintains cellular functions. Emerging evidence has revealed an intrinsic connection between autophagy and macrophage functions. This review focuses on the role and underlying mechanisms of autophagy‐mediated regulation of macrophage plasticity in polarization, inflammasome activation, cytokine secretion, metabolism, phagocytosis, and the number of macrophages. In addition, autophagy has been shown to connect macrophages and heart cells. It is attributed to specific substrate degradation or signalling pathway activation by autophagy‐related proteins. Referring to the latest reports, applications targeting macrophage autophagy have been discussed in CVDs, such as atherosclerosis, myocardial infarction, heart failure, and myocarditis. This review describes a novel approach for future CVD therapies.

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miR-424/322 attenuates cardiac remodeling by modulating the nuclear factor-activated T-cell 3/furin pathway

Tsai,

Wang,

Hsu

et al. 2024

Biomedical Journal

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FURIN suppresses the progression of atherosclerosis by promoting macrophage autophagy

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 7 publications

References 48 publications

Functional Roles of Furin in Cardio-Cerebrovascular Diseases

Functional Roles of Furin in Cardio-Cerebrovascular Diseases

Comprehensive view of macrophage autophagy and its application in cardiovascular diseases

miR-424/322 attenuates cardiac remodeling by modulating the nuclear factor-activated T-cell 3/furin pathway

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