Genistein suppresses smooth muscle cell-derived foam cell formation through tyrosine kinase pathway

Lin, Jinghan; Xu, Yi; Zhao, Tingting; Sun, Lina; Yang, Meimei; Liu, Tingjiao; Sun, Hui; Zhang, Liming

doi:10.1016/j.bbrc.2015.04.155

Cited by 13 publications

(5 citation statements)

References 38 publications

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“…LOX-1 mediated signaling has been implicated in the development and progression of cardiovascular diseases 14, 27) . By interacting with ox-LOX-1, LOX-1 acts as a key regulator in activating endothelial cells, promoting the adhesion ability of monocytes to the endothelium, and altering VSMCs phenotype by increasing the levels of inflammatory chemokines and adhesion molecules, including monocyte chemotactic protein 1 (MCP-1), E-selectin, P-selectin, and vascular cell adhesion molecule-1 (VCAM-1) 28–30) . In ApoE knockout mice, pretreatment with an anti-LOX-1 antibody partly recovered the endothelial-dependent diastolic dysfunction of the micro coronary artery induced by high-fat diet 31, 32) .…”

Section: Discussionmentioning

confidence: 99%

Association of the LOX-1 rs1050283 Polymorphism with Risk for Atherosclerotic Cerebral Infarction and its Effect on sLOX-1 and LOX-1 Expression in a Chinese Population

Guo

Xiang

Yang

et al. 2017

J Atheroscler Thromb

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Aims: The interaction between lectin-like oxidized low density lipoprotein (LDL) receptor-1 (LOX-1) and oxidized LDL (ox-LDL) has been viewed as an important pathogenic factor for cardiovascular diseases. This study aimed to explore the association of a functional polymorphism rs1050283 in the 3′-untranslated region of the LOX-1 gene with atherosclerotic cerebral infarction (ACI) susceptibility, and we also investigated the effects of the rs1050283 polymorphism on LOX-1 expression and serum levels of sLOX-1 in patients with ACI.Methods: A case-controlled study was performed in 526 patients with ACI and 640 healthy controls. Genotyping was performed by DNA sequencing method. Real-time PCR and Western blotting were used to determine the level of LOX-1 expression. Serum levels of sLOX-1 were quantified using ELISA according to the manufacturer's instruction.Results: The results of the present study showed that the frequency of rs1050283 T allele was significantly higher in patients with ACI than in healthy controls. We also found that the rs1050283 polymorphism T allele was associated with increased LOX-1 expression at mRNA and protein levels in patients with ACI. Furthermore, we also observed that among patients with ACI, those with the rs1050283 T allele showed an increased serum level of sLOX-1.Conclusion: Our research demonstrated that the rs1050283 T allele of LOX-1 is strongly associated with an increased risk for ACI in a Chinese population, which also affects levels of LOX-1 and sLOX-1.

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Section: Discussionmentioning

confidence: 99%

Association of the LOX-1 rs1050283 Polymorphism with Risk for Atherosclerotic Cerebral Infarction and its Effect on sLOX-1 and LOX-1 Expression in a Chinese Population

Guo

Xiang

Yang

et al. 2017

J Atheroscler Thromb

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“…Douchi is used as a complementary and alternative medicine in the treatment of heat-related disease such as heartburn, inflammation and common cold [21]. It was found that it contains isoflavones such as genistein, daidzein [22], and its components are known to have an effect of regulating PKC and Th2 response in inflammatory disorders [23–25]. Several animal studies also reported that fermented soybeans, which is similar to Douchi, have therapeutic effects on inflammatory allergic diseases that involve Th2 immunomodulatory activity [26, 27].…”

Section: Introductionmentioning

confidence: 99%

Douchi (fermented Glycine max Merr.) alleviates atopic dermatitis-like skin lesions in NC/Nga mice by regulation of PKC and IL-4

Jung

Ahn

Park

et al. 2016

BMC Complement Altern Med

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BackgroundDouchi (fermented Glycine max Merr.) is produced from fermented soybeans, which is widely used in traditional herbal medicine. In this study, we investigated whether Douchi attenuates protein kinase C (PKC) and interleukin (IL)-4 response and cutaneous inflammation in Atopic dermatitis (AD)-like NC/Nga mice.MethodsTo induce AD-like skin lesions, D. farinae antigen was applied to the dorsal skin of 3-week-old NC/Nga mice. After inducing AD, Douchi extract was administered 20 mg/kg daily for 3 weeks to the Douchi-treated mice group. We identified the changes of skin barrier and Th2 differentiation through PKC and IL-4 by immunohistochemistry.ResultsDouchi treatment of NC/Nga mice significantly reduced clinical scores (p < 0.01) and histological features. The levels of PKC and IL-4 were significantly reduced in the Douchi-treated group (p < 0.01). The reduction of IL-4 and PKC led to decrease of inflammatory factors such as substance P, inducible nitric oxide synthase (iNOS) and Matrix metallopeptidase 9 (MMP-9) (all p < 0.01). Douchi also down-regulated Th1 markers (IL-12, TNF-α) as well as Th2 markers (IL-4, p-IκB) (p < 0.01).ConclusionDouchi alleviates AD-like skin lesions through suppressing of PKC and IL-4. These results also lead to diminish levels of substance P, iNOS and MMP-9 in skin lesions. Therefore, Douchi may have potential applications for the prevention and treatment of AD.

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“…Besides, a prior work unraveled that genistein resulted in the decrease in VSMC proliferation and migration during neointima formation (33). Genistein could suppress VSMCderived foam cell formation through the downregulation of LOX-1 by blocking tyrosine kinase pathway (34). Furthermore, our work exhibited that inhibition of L-Ca channels participated in the suppressive impacts of genistein on ox-LDL-induced VSMC proliferation, migration, and foaming.…”

Section: Discussionmentioning

confidence: 51%

Anti-atherosclerotic effects of genistein in preventing ox-low-density lipoprotein-induced smooth muscle-derived foam cell formation via inhibiting SRC expression and L-Ca channel currents

Zhang¹,

Zhang²,

Zhang³

2022

Ann Transl Med

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Background: Atherosclerosis (AS) is associated with inflammation and abnormal proliferation and migration of vascular smooth muscle cells (VSMCs). Genistein may curtail the migration of VSMCs.Therefore, explorations are required to determine the molecular mechanism of genistein in AS. In this context, animal and cell models were developed to ascertain mechanisms of genistein in AS by modulating VSMC activities. Methods: Genistein treatment and ectopic expression of lectin-like oxidized LDL receptor-1 (LOX-1) were conducted in high-fat diet-induced AS rats, followed by analyses of atherosclerotic plaque lesion areas and lipid deposition using Oil Red O and hematoxylin and eosin (HE) staining. The isolated VSMCs were stimulated with oxidized low-density lipoprotein (ox-LDL). Following genistein treatment combined with gain-and loss-of-function experiments in ox-LDL-exposed VSMCs, viability, migration, intracellular lipid deposition, intracellular cholesterol content, and L-type calcium (L-Ca) channel currents were assessed using Cell Counting Kit-8 (CCK-8), scratch test, Oil Red O staining, enzymatic colorimetry, and patchclamp experiments, respectively. Western blot analysis was performed to evaluate the protein expression of SRC proto-oncogene, non-receptor tyrosine kinase (SRC), calcium voltage-gated channel subunit alpha1 C (CACNA1C), and LOX-1. Results: Genistein treatment counteracted upregulated SRC phosphorylation, CACNA1C and LOX-1 expression, and L-Ca channel currents in aortic tissues of AS rats and ox-LDL-exposed VSMCs. Genistein deceased L-Ca channel currents by downregulating SRC, and SRC augmented LOX-1 expression by acting on the L-Ca channel subunit CACNA1C. The ox-LDL-induced VSMC proliferation, migration, and foaming of VSMCs were reduced by genistein treatment, silencing SRC, CACNA1C, or LOX-1, or suppressing L-Ca channels. Genistein treatment diminished atherosclerotic plaque lesion formation and lipid deposition, and these results were annulled by upregulating LOX-1. Conclusions: Collectively, genistein might block the SRC/CACNA1C/LOX-1 axis to impede ox-LDLinduced VSMC proliferation, migration, and foaming and alleviate AS formation.

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Genistein suppresses smooth muscle cell-derived foam cell formation through tyrosine kinase pathway

Cited by 13 publications

References 38 publications

Association of the LOX-1 rs1050283 Polymorphism with Risk for Atherosclerotic Cerebral Infarction and its Effect on sLOX-1 and LOX-1 Expression in a Chinese Population

Association of the LOX-1 rs1050283 Polymorphism with Risk for Atherosclerotic Cerebral Infarction and its Effect on sLOX-1 and LOX-1 Expression in a Chinese Population

Douchi (fermented Glycine max Merr.) alleviates atopic dermatitis-like skin lesions in NC/Nga mice by regulation of PKC and IL-4

Anti-atherosclerotic effects of genistein in preventing ox-low-density lipoprotein-induced smooth muscle-derived foam cell formation via inhibiting SRC expression and L-Ca channel currents

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