scholarly journals Inhibition of Aortic Intimal Hyperplasia and Vascular Smooth Muscle Proliferation and Extracellular Matrix Protein Expressions by Astragalus–Angelica Combination

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Huifang Yan ◽  
Xiwei Peng ◽  
Hao Xu ◽  
Jiahuan Zhu ◽  
Changqing Deng
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Intimal Hyperplasia ◽  
Matrix Protein ◽  
Vascular Wall ◽  
Extracellular Matrix Protein ◽  
Nuclear Antigen ◽  
Balloon Injury ◽  
Vsmc Proliferation ◽  
Pathway Activation

VSMC proliferation and ECM deposition always resulted in intimal hyperplasia. Astragalus–Angelica combination has a protective effect on the cardiovascular system. The inhibition effect of different Astragalus–Angelica combination on the hyperplastic intima after vascular balloon injury in rats was investigated in this study. Astragalus–Angelica combination can inhibit the intima hyperplasia after balloon injury, in which a 1:1 ratio shows excellent results. Astragalus–Angelica combination can enhance the expression of smooth muscleα-actin (SMа-actin) and inhibit the expression of proliferating cell nuclear antigen (PCNA), cyclin D1, cyclin E, collagen I (Col-I), fibronectin (FN), and matrix metallopeptidase-9 (MMP-9) in hyperplastic intima, suggesting that Astragalus–Angelica combination can inhibit the intimal hyperplasia of blood vessels in rats. The mechanism is related to the inhibition of PI3K/Akt signaling pathway activation and thereby inhibits the phenotypic transformation and cell proliferation of VSMCs and thus inhibits the extracellular matrix (ECM) deposition of vascular wall during intimal hyperplasia.

scholarly journals Ablation of the miRNA Cluster 24 Has Profound Effects on Extracellular Matrix Protein Abundance in Cartilage

2020 ◽  
Vol 21 (11) ◽  
pp. 4112
Author(s):  
Veronika S. Georgieva ◽  
Julia Etich ◽  
Björn Bluhm ◽  
Mengjie Zhu ◽  
Christian Frie ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Matrix Protein ◽  
Immunoblot Analysis ◽  
Extracellular Matrix Protein ◽  
Mirna Cluster ◽  
Rna Molecules ◽  
Genetic Ablation ◽  
Pathway Activation ◽  
Matrix Metallopeptidase

MicroRNAs (miRNAs) regulate cartilage differentiation and contribute to the onset and progression of joint degeneration. These small RNA molecules may affect extracellular matrix organization (ECM) in cartilage, but for only a few miRNAs has this role been defined in vivo. Previously, we showed that cartilage-specific genetic ablation of the Mirc24 cluster in mice leads to impaired cartilage development due to increased RAF/MEK/ERK pathway activation. Here, we studied the expression of the cluster in cartilage by LacZ reporter gene assays and determined its role for extracellular matrix homeostasis by proteome and immunoblot analysis. The cluster is expressed in prehypertrophic/hypertrophic chondrocytes of the growth plate and we now show that the cluster is also highly expressed in articular cartilage. Cartilage-specific loss of the cluster leads to increased proteoglycan 4 and matrix metallopeptidase 13 levels and decreased aggrecan and collagen X levels in epiphyseal cartilage. Interestingly, these changes are linked to a decrease in SRY-related HMG box-containing (SOX) transcription factors 6 and 9, which regulate ECM production in chondrocytes. Our data suggests that the Mirc24 cluster is important for ECM homoeostasis and the expression of transcriptional regulators of matrix production in cartilage.

scholarly journals The mTOR/p70 S6K1 pathway regulates vascular smooth muscle cell differentiation

2004 ◽  
Vol 286 (3) ◽  
pp. C507-C517 ◽  
Author(s):  
Kathleen A. Martin ◽  
Eva M. Rzucidlo ◽  
Bethany L. Merenick ◽  
Diane C. Fingar ◽  
David J. Brown ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Intimal Hyperplasia ◽  
Transcriptional Control ◽  
Matrix Protein ◽  
Kinase Inhibitors ◽  
Extracellular Matrix Protein ◽  
Induced Expression ◽  
Synthetic Phenotype

Vascular smooth muscle cells (VSMC) in mature, normal blood vessels exhibit a differentiated, quiescent, contractile morphology, but injury induces a phenotypic modulation toward a proliferative, dedifferentiated, migratory phenotype with upregulated extracellular matrix protein synthesis (synthetic phenotype), which contributes to intimal hyperplasia. The mTOR (the mammalian target of rapamycin) pathway inhibitor rapamycin inhibits intimal hyperplasia in animal models and in human clinical trials. We report that rapamycin treatment induces differentiation in cultured synthetic phenotype VSMC from multiple species. VSMC treated with rapamycin assumed a contractile morphology, quantitatively reflected by a 67% decrease in cell area. Total protein and collagen synthesis were also inhibited by rapamycin. Rapamycin induced expression of the VSMC differentiation marker contractile proteins smooth muscle (SM) α-actin, calponin, and SM myosin heavy chain (SM-MHC), as observed by immunoblotting and immunohistochemistry. Notably, we detected a striking rapamycin induction of calponin and SM-MHC mRNA, suggesting a role for mTOR in transcriptional control of VSMC gene expression. Rapamycin also induced expression of the cyclin-dependent kinase inhibitors p21cip and p27kip, consistent with cell cycle withdrawal. Rapamycin inhibits mTOR, a signaling protein that regulates protein synthesis effectors, including p70 S6K1. Overexpression of p70 S6K1 inhibited rapamycin-induced contractile protein and p21cip expression, suggesting that this kinase opposes VSMC differentiation. In conclusion, we report that regulation of VSMC differentiation is a novel function of the rapamycin-sensitive mTOR signaling pathway.

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