Crocin prevents platelet‑derived growth factor BB‑induced vascular smooth muscle cells proliferation and phenotypic switch

Tong, Lijian; Qi, Guoxian

doi:10.3892/mmr.2018.8854

Cited by 16 publications

(12 citation statements)

References 39 publications

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“…Atheromatosis is known to increase the vascular wall thickness, which decreases oxygen diffusion to the wall layers and causes tissue hypoxia [30]. Smooth muscle cell proliferation is a key component of this process and crocin has been found to decrease smooth muscle cell proliferation [31].…”

Section: Discussionmentioning

confidence: 99%

Mechanistic insights on the effect of crocin, an active ingredient of saffron, on atherosclerosis in apolipoprotein E knockout mice

Makaritsis

Kotidis

Papacharalampous

et al. 2022

Coronary Artery Disease

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Background We investigated the effect of crocin treatment on atherosclerosis and serum lipids in apolipoprotein E knockout (ApoE−/−) mice, focusing on the expression of endothelial nitric oxide synthase (eNOS) and hypoxia-induced factor-1 alpha (HIF-1α). Methods Sixty-two animals were divided into two groups and randomly allocated to crocin (100 mg/kg/day) in drinking water or no crocin. All mice were maintained on standard chow diet containing 5% fat. Crocin was initiated at the 16th week of age and continued for 16 additional weeks. At 32 weeks of age, after blood sampling for plasma lipid determination and euthanasia, proximal aorta was removed and 3 μm sections were used to measure the atherosclerotic area and determine the expression of eNOS and HIF-1α by immunohistochemistry. Results Each group consisted of 31 animals (17 males and 14 females in each group). Crocin significantly reduced the atherosclerotic area (mm2 ± SEM) in treated mice compared to controls, both in males (0.0798 ± 0.017 vs. 0.1918 ± 0.028, P < 0.002, respectively) and females (0.0986 ± 0.023 vs. 0.1765 ± 0.025, P < 0.03, respectively). eNOS expression was significantly increased in crocin-treated mice compared to controls, both in males (2.77 ± 0.24 vs. 1.50 ± 0.34, P=0.004, respectively) and females (3.41 ± 0.37 vs. 1.16 ± 0.44, P=0.003, respectively). HIF-1α expression was significantly decreased in crocin-treated mice compared to controls, both in males (21.25 ± 2.14 vs. 156.5 ± 6.67, P < 0.001, respectively) and females (35.3 ± 7.20 vs. 113.3 ± 9.0, P < 0.01, respectively). No difference was noticed in total, low- and high-density lipoprotein cholesterol between treated and control mice. Conclusion Crocin reduces atherosclerosis possibly by modulation of eNOS and HIF-1α expression in ApoE−/− mice without affecting plasma cholesterol.

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Section: Discussionmentioning

confidence: 99%

Mechanistic insights on the effect of crocin, an active ingredient of saffron, on atherosclerosis in apolipoprotein E knockout mice

Makaritsis

Kotidis

Papacharalampous

et al. 2022

Coronary Artery Disease

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“…These results suggest that synthetic phenotype marker switching is dependent on CTGF. According to previous studies, the expression interaction between synthetic and contractile markers tends to be inversely proportional [ 9 , 35 ]. However, it is unlikely that the expressions of both markers always have an inversely proportional relationship.…”

Section: Discussionmentioning

confidence: 99%

Kahweol, a Diterpenoid Molecule, Inhibits CTGF-Dependent Synthetic Phenotype Switching and Migration in Vascular Smooth Muscle Cells

2021

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Vascular smooth muscle cell (VSMC) phenotype switching from contractile to synthetic is essential for proliferation and migration in vascular pathophysiology. Connective tissue growth factor (CTGF) is a matricellular protein involved in cell adhesion, migration, and proliferation. Kahweol, a diterpene molecule in arabica coffee beans, has been reported to have anti-inflammatory, antiproliferative, and apoptotic effects in many cells. However, in VSMCs, the effects of kahweol on CTGF activities have not been investigated. Thus, in this study, the effects and associated mechanisms of kahweol in CTGF-dependent phenotype switching and migration in VSMCs were examined. Experiments were performed on primary rat aortic smooth muscle cells and a rat VSMC line, A7r5. Western blot analysis was used to determine the protein levels. The mRNA levels of synthetic markers were measured by qRT-PCR. Migration of VSMCs was evaluated by wound healing and transwell assays. Kahweol reduced the angiotensin II (Ang II)-induced CTGF expression. Further, kahweol inhibited expressions of synthetic phenotype markers of VSMC. The kahweol-reduced synthetic marker protein levels were reversed by the administration of rCTGF. However, expressions of contractile phenotype markers of VSMC were not affected. Kahweol suppressed Ang II-stimulated VSMC migration. Moreover, kahweol downregulated Ang II-induced p-FAK, p-Erk, and Yes-associated protein (YAP) protein expressions. Taken together, in Ang II-stimulated VSMCs, kahweol inhibited CTGF-dependent synthetic phenotype switching and migration, with focal adhesion kinase (FAK), Erk, and YAP involved in the underlying mechanisms of the kahweol effects. These results suggest that kahweol has a potential as a therapeutic agent to inhibit CTGF, which is a molecular target in sclerogenic vascular disease.

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“…Interestingly, PDGF-BB has also been implicated in the pathogenesis of coronary atherosclerosis (44), a common non-AIDS-defining disorder, with a prevalence twice that of HIVuninfected persons (45). In this setting, disease pathogenesis involves PDGF-BB-mediated induction of smooth muscle cell proliferation together with phenotypic changes to these cells, promoting migration and formation of neointima (46,47).…”

Section: Discussionmentioning

confidence: 99%

Differential Responsiveness of the Platelet Biomarkers, Systemic CD40 Ligand, CD62P, and Platelet-Derived Growth Factor-BB, to Virally-Suppressive Antiretroviral Therapy

et al. 2021

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Systemic biomarkers of inflammation, including cytokines and chemokines, are potentially useful in the management of both HIV infection and non-AIDS-defining disorders. However, relatively little is known about the utility of measurement of circulating biomarkers of platelet activation as a strategy to monitor the efficacy of combination antiretroviral therapy (cART), as well as the persistence of systemic inflammation following virally-suppressive therapy in HIV-infected persons. These issues have been addressed in the current study to which a cohort consisting of 199 HIV-infected participants was recruited, 100 of whom were cART-naïve and the remainder cART-treated and virally-suppressed. Fifteen healthy control participants were included for comparison. The study focused on the effects of cART on the responsiveness of three biomarkers of platelet activation, specifically soluble CD40 ligand (sCD40L), sCD62P (P-selectin), and platelet-derived growth factor-BB (PDGF-BB), measured using multiplex suspension bead array technology. Most prominently sCD40L in particular, as well as sCD62P, were significantly elevated in the cART-naïve group relative to both the cART-treated and healthy control groups. However, levels of PDGF-BB were of comparable magnitude in both the cART-naïve and –treated groups, and significantly higher than those of the control group. Although remaining somewhat higher in the virally-suppressed group relative to healthy control participants, these findings identify sCD40L, in particular, as a potential biomarker of successful cART, while PDGF-BB may be indicative of persistent low-level antigenemia.

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Crocin prevents platelet‑derived growth factor BB‑induced vascular smooth muscle cells proliferation and phenotypic switch

Cited by 16 publications

References 39 publications

Mechanistic insights on the effect of crocin, an active ingredient of saffron, on atherosclerosis in apolipoprotein E knockout mice

Mechanistic insights on the effect of crocin, an active ingredient of saffron, on atherosclerosis in apolipoprotein E knockout mice

Kahweol, a Diterpenoid Molecule, Inhibits CTGF-Dependent Synthetic Phenotype Switching and Migration in Vascular Smooth Muscle Cells

Differential Responsiveness of the Platelet Biomarkers, Systemic CD40 Ligand, CD62P, and Platelet-Derived Growth Factor-BB, to Virally-Suppressive Antiretroviral Therapy

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