scholarly journals Runx2 deletion in smooth muscle cells inhibits vascular osteochondrogenesis and calcification but not atherosclerotic lesion formation

2016 ◽  
Vol 112 (2) ◽  
pp. 606-616 ◽  
Author(s):  
Mu-En Lin ◽  
Theodore M. Chen ◽  
Mary C. Wallingford ◽  
Ngoc B. Nguyen ◽  
Shunsuke Yamada ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Atherosclerotic Lesion ◽  
Muscle Cells ◽  
Lesion Formation ◽  
Atherosclerotic Lesion Formation

Abstract 436: Smooth Muscle Specific Knock-out of the Zinc-Finger Protein 148(ZFP148) Attenuates Atherosclerotic Lesion Formation via Regulation of Apoptotic Signaling Pathways

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Morgan Salmon ◽  
Anna Z Fashandi ◽  
Michael D Spinosa ◽  
Ashish K Sharma ◽  
Gary K Owens ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Zinc Finger Protein ◽  
Atherosclerotic Lesion ◽  
Muscle Cells ◽  
Lesion Size ◽  
Western Diet ◽  
Lesion Formation ◽  
Knock Out ◽  
Atherosclerotic Lesion Formation

Objective: Zinc-finger protein 148 (ZFP148) plays a profound role in the modulation of aortic aneurysm formation in part via modulation of smooth muscle (SMC) genes. The current study objective was to determine whether smooth muscle specific knock-out of ZFP148 is critical in atherosclerotic lesion formation. Methods: ZFP148 was examined via immunohistochemistry and confocal microscopy in human atherosclerotic lesion samples (n=12/group). 6-8 week male (n=12/group) ZFP flx/flx Myh11 Cre+ ApoE-/-(SMC tamoxifen ZFP148 KO), Myh11 ZFP148 flx/wt Cre+ ApoE-/- and Myh11 ZFP wt/wt Cre+ ApoE-/- underwent tamoxifen injections followed by western diet feeding for either 13 or 25 weeks. A separate set of mice were fed western diet for 18 weeks and then administered tamoxifen injections. Aortic samples were evaluated with histology for α-actin, macrophages, neutrophils, TER119, caspase3, Ki67, picosirus red and movat staining. In vitro ZFP148 was knocked down using siRNA in smooth muscle cells and stimulated with the oxidized phospholipid POVPC. Results: ZFP148 expression was elevated in human atherosclerotic lesion samples and localized to smooth muscle cells. Lesion size was significantly reduced in SMC ZFP148 KO mice compared with controls in 25 week western diet fed mice(p<0.0357). SMC ZFP148 KO demonstrated reduced macrophage, Caspase3, and TER119 staining. Conversely, SMC ZFP148 KO increased SMα-actin coverage. Lesion size was also decreased in mice that were administered tamoxifen injections following 18 weeks of western diet feeding(p<0.0415). There were no significant changes in lesion size at 13 weeks of western diet feeding; however, macrophage staining was decreased. Knock-down of ZFP148 followed by treatment with POVPC attenuated the down-regulation of SM22α, SM-MHC, and SMαA. Knock-down of ZFP148 followed by POVPC treatment also prevented the up-regulation of Bax and BAD in vascular smooth muscle cells. Conclusions: While earlier studies documented a role for ZFP148 in aneurysm disease, the present study suggests that SMC ZFP148 KO attenuates atherosclerotic lesion formation in early and late atherosclerotic disease. ZFP148 represents a key regulator of multiple types of vascular disease.

scholarly journals Dominant negative PPARγ promotes atherosclerosis, vascular dysfunction, and hypertension through distinct effects in endothelium and vascular muscle

2013 ◽  
Vol 304 (9) ◽  
pp. R690-R701 ◽  
Author(s):  
Christopher J. Pelham ◽  
Henry L. Keen ◽  
Steven R. Lentz ◽  
Curt D. Sigmund
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Type Ii Diabetes ◽  
Atherosclerotic Lesion ◽  
Dominant Negative ◽  
Type Ii ◽  
Lesion Formation ◽  
Specific Expression ◽  
Altered Expression ◽  
Atherosclerotic Lesion Formation

Agonists of the nuclear hormone receptor peroxisome proliferator-activated receptor γ (PPARγ) have potent insulin-sensitizing effects and inhibit atherosclerosis progression in patients with Type II diabetes. Conversely, missense mutations in the ligand-binding domain of PPARγ that render the transcription factor dominant negative (DN) cause early-onset hypertension and Type II diabetes. We tested the hypothesis that DN PPARγ-mediated interference of endogenous wild-type PPARγ in the endothelium and vascular smooth muscle exacerbates atherosclerosis in apolipoprotein E-deficient (ApoE−/−) mice. Endothelium-specific expression of DN PPARγ on the ApoE−/− background unmasked significant impairment of endothelium-dependent relaxation in aortic rings, increased systolic blood pressure, altered expression of atherogenic markers (e.g., Cd36, Mcp1, Catalase), and enhanced diet-induced atherosclerotic lesion formation in aorta. Smooth muscle-specific expression of DN PPARγ, which induces aortic dysfunction and increased systolic blood pressure at baseline, also resulted in enhanced diet-induced atherosclerotic lesion formation in aorta on the ApoE−/− background that was associated with altered expression of a shared, yet distinct, set of atherogenic markers (e.g., Cd36, Mcp1, Osteopontin, Vcam1). In particular, induction of Osteopontin expression by smooth muscle-specific DN PPARγ correlated with increased plaque calcification. These data demonstrate that inhibition of PPARγ function specifically in the vascular endothelium or smooth muscle may contribute to cardiovascular disease.

scholarly journals Influence of conjugated linoleic acids on functional properties of vascular cells

2009 ◽  
Vol 102 (8) ◽  
pp. 1099-1116 ◽  
Author(s):  
Robert Ringseis ◽  
Klaus Eder
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Functional Properties ◽  
Inflammatory Responses ◽  
Atherosclerotic Lesion ◽  
Muscle Cells ◽  
Vascular Wall ◽  
Mechanisms Of Action ◽  
Conjugated Linoleic Acids

Conjugated linoleic acids (CLA) are biologically highly active lipid compounds that inhibit the development of atherosclerotic plaques in experimental animals. The underlying mechanisms of action, however, are only poorly understood. Since cell-culture experiments are appropriate to provide a detailed view into the mechanisms of action of a compound, the present review summarises results from in vitro studies dealing with the effects of CLA isomers and CLA mixtures on functional properties of cells of the vascular wall, such as endothelial cells, smooth muscle cells and monocyte-derived macrophages, which are amongst the major cells contributing to atherosclerotic lesion development. Based on these studies, it can be concluded that CLA exert several beneficial actions in cells of the vascular wall through the activation of nuclear PPAR. These actions of CLA, which may, at least partially, explain the inhibition of atherogenesis by dietary CLA, include modulation of vasoactive mediator release from endothelial cells, inhibition of inflammatory and fibrotic processes in activated smooth muscle cells, abrogation of inflammatory responses in activated macrophages, and reduction of cholesterol accumulation in macrophage-derived foam cells.

scholarly journals The LIM-Only Protein FHL2 Reduces Vascular Lesion Formation Involving Inhibition of Proliferation and Migration of Smooth Muscle Cells

PLoS ONE ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. e94931 ◽  
Author(s):  
Kondababu Kurakula ◽  
Mariska Vos ◽  
Iker Otermin Rubio ◽  
Goran Marinković ◽  
Reinhard Buettner ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Vascular Lesion ◽  
Lesion Formation ◽  
Inhibition Of Proliferation ◽  
And Migration ◽  
Proliferation And Migration

scholarly journals Apigenin Retards Atherogenesis by Promoting ABCA1-Mediated Cholesterol Efflux and Suppressing Inflammation

2018 ◽  
Vol 47 (5) ◽  
pp. 2170-2184 ◽  
Author(s):  
Kun Ren ◽  
Ting Jiang ◽  
Hui-Fang Zhou ◽  
Yin Liang ◽  
Guo-Jun Zhao
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Inflammatory Cytokines ◽  
Cholesterol Efflux ◽  
Atherosclerotic Lesion ◽  
Muscle Cells ◽  
Dependent Manner ◽  
Cellular Cholesterol ◽  
Abca1 Expression ◽  
Pro Inflammatory Cytokines

Background/Aims: The development of atherosclerosis is accompanied by escalating inflammation and lipid accumulation within blood vessel walls. ABCA1 plays a crucial role in mediating cholesterol efflux from macrophages, which protects against atherogenesis. This research was designed to explore the effects and underlying mechanisms of apigenin (4’, 5, 7-trihydroxyflavone) on ABCA1-mediated cellular cholesterol efflux and LPS-stimulated inflammation in RAW264.7 macrophages and apoE-/- mice. Methods: Expression of genes or proteins was examined by RT-PCR or western blot analysis. Liquid scintillation counting was used to detect percent cholesterol efflux. Cellular cholesterol content was measured using HPLC assay. The secretion levels of pro-inflammatory cytokines were quantified by ELISA assay. Atherosclerotic lesion sizes were determined with Oil Red O staining. The contents of macrophages and smooth muscle cells in atherosclerotic lesion were evaluated using immunohistochemistry. Plasma TC, TG, HDL-C and LDL-C levels in apoE-/- mice were evaluated using commercial test kits. Results: Apigenin potently increased ABCA1 expression through miR-33 repression in a dose- and time-dependent manner. Treatment with apigenin significantly increased ABCA1-mediated cholesterol efflux, and reduced TC, FC and CE levels in macrophage-derived foam cells. In LPS-treated macrophages, the expression levels of TLR-4, MyD88 and p-IκB-α as well as nuclear NF-κB p65 were decreased by the addition of apigenin. Moreover, apigenin markedly decreased secretion levels of several pro-inflammatory cytokines. Lastly, in LPS-challenged apoE-/- mice, apigenin administration augmented ABCA1 expression, decreased the contents of macrophages and smooth muscle cells in atherosclerotic lesion, reduced miR-33, TLR-4, and NF-κB p65 levels, improved plasma lipid profile and relieved inflammation, which results in less atherosclerotic lesion size. Conclusions: Taken together, these results suggest that apigenin may attenuate atherogenesis through up-regulating ABCA1-mediated cholesterol efflux and inhibiting inflammation.

scholarly journals Human Activin-A Is Expressed in the Atherosclerotic Lesion and Promotes the Contractile Phenotype of Smooth Muscle Cells

1999 ◽  
Vol 85 (10) ◽  
pp. 931-939 ◽  
Author(s):  
Marten A. Engelse ◽  
Jolanda M. Neele ◽  
Tanja A. E. van Achterberg ◽  
Benien E. van Aken ◽  
Ron H. N. van Schaik ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Atherosclerotic Lesion ◽  
Muscle Cells ◽  
Activin A ◽  
Contractile Phenotype

scholarly journals Vascular smooth muscle cells in atherosclerosis: time for a re-assessment

2021 ◽  
Author(s):  
Mandy O J Grootaert ◽  
Martin R Bennett
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Atherosclerotic Lesion ◽  
Muscle Cells ◽  
Lineage Tracing ◽  
Phenotypic Switching ◽  
Fibrous Cap ◽  
The Media

Abstract Vascular smooth muscle cells (VSMCs) are key participants in both early and late-stage atherosclerosis. VSMCs invade the early atherosclerotic lesion from the media, expanding lesions, but also forming a protective fibrous cap rich in extracellular matrix to cover the ‘necrotic’ core. Hence, VSMCs have been viewed as plaque-stabilizing, and decreased VSMC plaque content—often measured by expression of contractile markers—associated with increased plaque vulnerability. However, the emergence of lineage-tracing and transcriptomic studies has demonstrated that VSMCs comprise a much larger proportion of atherosclerotic plaques than originally thought, demonstrate multiple different phenotypes in vivo, and have roles that might be detrimental. VSMCs down-regulate contractile markers during atherosclerosis whilst adopting alternative phenotypes, including macrophage-like, foam cell-like, osteochondrogenic-like, myofibroblast-like, and mesenchymal stem cell-like. VSMC phenotypic switching can be studied in tissue culture, but also now in the media, fibrous cap and deep-core region, and markedly affects plaque formation and markers of stability. In this review, we describe the different VSMC plaque phenotypes and their presumed cellular and paracrine functions, the regulatory mechanisms that control VSMC plasticity, and their impact on atherogenesis and plaque stability.

Sign in / Sign up

Export Citation Format

Share Document