Effects of flavonoids on MicroRNA 145 regulation through Klf4 and myocardin in neointimal formation in vitro and in vivo

Lin, Chiu Mei; Wang, Bao Wei; Pan, Chun Ming; Fang, Wei; Chua, Su Kiat; Hou, Sheng Wen; Chang, Hang; Shyu, Kou‐Gi

doi:10.1016/j.jnutbio.2017.08.016

Cited by 13 publications

(7 citation statements)

References 36 publications

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“…3f). Due to the low expression of KLF4 in normal SMCs, all the experimental groups were treated with Ang II primarily, which could improve the expression of KLF4 in SMCs 47 . The significantly deeper band in the Ang II group than the blank group illustrated the successful upregulation of KLF4 in SMCs.…”

Section: Resultsmentioning

confidence: 99%

Multifunctional cationic nanosystems for nucleic acid therapy of thoracic aortic dissection

Xu¹,

Zhang

et al. 2019

Nat Commun

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Thoracic aortic dissection (TAD) is an aggressive vascular disease that requires early diagnosis and effective treatment. However, due to the particular vascular structure and narrowness of lesion location, there are no effective drug delivery systems for the therapy of TAD. Here, we report a multifunctional delivery nanosystem (TP-Gd/miRNA-ColIV) composed of gadolinium-chelated tannic acid (TA), low-toxic cationic PGEA (ethanolamine-aminated poly(glycidyl methacrylate)) and type IV collagen targeted peptide (ColIV) for targeted nucleic acid therapy, early diagnosis and noninvasive monitoring of TAD. Such targeted therapy with miR-145 exhibits impressive performances in stabilizing the vascular structures and preventing the deterioration of TAD. After the treatment with TP-Gd/miR-145-ColIV, nearly no dissection occurs in the thoracic aortic arches of the mice with TAD model. Moreover, TP-Gd/miRNA-ColIV also demonstrates good magnetic resonance imaging (MRI) ability and can be used to noninvasively monitor the development conditions of TAD.

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Section: Resultsmentioning

confidence: 99%

Multifunctional cationic nanosystems for nucleic acid therapy of thoracic aortic dissection

Xu¹,

Zhang

et al. 2019

Nat Commun

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“…Recently, many elements have been confirmed by scientists to play a critical role in the development of VSMC function and arteriosclerosis, such as miR-125b, miR-145, miR-21, miR-206, etc. [46][47][48][49]. Because miR-125a-3p has a significant impact on the cellular events of VSMCs in vitro, we hypothesized that miR-125a-3p has a high probability of playing a significant role in the process of vascular stenosis in vivo.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-125a-3p affects smooth muscle cell function in vascular stenosis

Chang

Zhang

et al. 2019

Journal of Molecular and Cellular Cardiology

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Many studies have indicated that microRNAs are closely related to the process of peripheral arterial disease (PAD). Previously, we found that microRNA-125a-3p (miR-125a-3p) in restenotic arteries after interventional therapy of lower extremity vessels was notably decreased compared with that of normal control arteries. However, its role in the development of vascular stenosis is not yet clearly understood. The purpose of this study was to investigate the expression, regulatory mechanism and function of miR-125a-3p in the process of vascular stenosis. Methods and results: Quantitative reverse-transcription polymerase chain reaction assays indicated that miR-125a-3p in restenotic arteries after interventional therapy was significantly lower than that in normal control arteries. Immunofluorescence and in situ hybridization co-staining assays in arterial sections demonstrated that miR-125a-3p was mainly expressed in the medial smooth muscle layer. Transfection of miR-125a-3p mimics into cultured vascular smooth muscle cells (VSMCs) effectively inhibited cell proliferation and migration. Then, western blot and luciferase activity assays showed that recombinant human mitogen-activated protein kinase 1 (MAPK1) was a functional target of miR-125a-3p and was involved in miR-125a-3p-mediated cell effects. Finally, the lentiviral infection of miR-125a-3p in balloon-injured rat carotid vascular walls showed that miR-125a-3p overexpression significantly reduced the probability of neointimal membrane production. Conclusions: miR-125a-3p can effectively inhibit the function of VSMCs and the occurrence of vascular stenosis by targeting MAPK1. This study introduces a new molecular mechanism of PAD. We show that regulation of the miR-125a-3p level has the potential to provide a new treatment for PAD and other proliferative vascular diseases. MicroRNAs are highly conserved single-stranded, non-coding RNA

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“…Moreover, MP effectively decreased the expression of basal and FBS-induced expression osteopontin, further emphasizing the maintenance of a contractile phenotype of VSMCs. In 2018, Lin et al showed that the flavonoid, (−)-epigallocatechin gallate (EGCG), attenuated Ag-II induced proliferation and migration in vitro and neointimal formation in vivo [125]. These inhibitory effects were mediated by myocardin.…”

Section: Discussionmentioning

confidence: 99%

7-O-Methylpunctatin, a Novel Homoisoflavonoid, Inhibits Phenotypic Switch of Human Arteriolar Smooth Muscle Cells

et al. 2019

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Remodeling of arterioles is a pivotal event in the manifestation of many inflammation-based cardio-vasculopathologies, such as hypertension. During these remodeling events, vascular smooth muscle cells (VSMCs) switch from a contractile to a synthetic phenotype. The latter is characterized by increased proliferation, migration, and invasion. Compounds with anti-inflammatory actions have been successful in attenuating this phenotypic switch. While the vast majority of studies investigating phenotypic modulation were undertaken in VSMCs isolated from large vessels, little is known about the effect of such compounds on phenotypic switch in VSMCs of microvessels (microVSMCs). We have recently characterized a novel homoisoflavonoid that we called 7-O-methylpunctatin (MP). In this study, we show that MP decreased FBS-induced cell proliferation, migration, invasion, and adhesion. MP also attenuated adhesion of THP-1 monocytes to microVSMCs, abolished FBS-induced expression of MMP-2, MMP-9, and NF-κB, as well as reduced activation of ERK1/2 and FAK. Furthermore, MP-treated VSMCs showed an increase in early (myocardin, SM-22α, SM-α) and mid-term (calponin and caldesmon) differentiation markers and a decrease in osteopontin, a protein highly expressed in synthetic VSMCs. MP also reduced transcription of cyclin D1, CDK4 but increased protein levels of p21 and p27. Taken together, these results corroborate an anti-inflammatory action of MP on human microVSMCs. Therefore, by inhibiting the synthetic phenotype of microVSMCs, MP may be a promising modulator for inflammation-induced arteriolar pathophysiology.

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Effects of flavonoids on MicroRNA 145 regulation through Klf4 and myocardin in neointimal formation in vitro and in vivo

Cited by 13 publications

References 36 publications

Multifunctional cationic nanosystems for nucleic acid therapy of thoracic aortic dissection

Multifunctional cationic nanosystems for nucleic acid therapy of thoracic aortic dissection

MicroRNA-125a-3p affects smooth muscle cell function in vascular stenosis

7-O-Methylpunctatin, a Novel Homoisoflavonoid, Inhibits Phenotypic Switch of Human Arteriolar Smooth Muscle Cells

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