scholarly journals Dynamic Interplay Between Smooth Muscle Cells and Macrophages in Vascular Disease

10.5772/61089 ◽  
2015 ◽  
Author(s):  
Hiroshi Iwata ◽  
Masanori Aikawa
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Disease ◽  
Muscle Cells ◽  
Dynamic Interplay

Abstract 144: A20 Inhibits Pathologic Interferon-? Signaling in Smooth Muscle Cells to Prevent Atherosclerotic Vascular Disease

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Herwig P Moll ◽  
Andy Lee ◽  
Christiane Ferran
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Disease ◽  
Muscle Cells ◽  
Interferon Γ ◽  
Atherosclerotic Vascular Disease ◽  
Human Coronary Artery ◽  
Protein Levels

The pleiotropic cytokine Interferon-γ (IFNγ), best known for its anti-viral and immunomodulatory activities, also demonstrates pro-atherogenic effects. Implication of IFNγ in the pathogenesis of atherosclerosis results in part from the upregulation of a number of pro-inflammatory interferon stimulated genes (ISGs) in vascular smooth muscle cells (SMC). Hence, strategies to reduce IFNγ signaling are of particular interest to reduce or prevent pathologic vascular remodeling associated with atherosclerotic disease, for instance transplant arteriosclerosis. We discovered that the anti-inflammatory and vasculoprotective protein A20 inhibits IFNγ signaling and thus the expression of ISG in vitro in human coronary artery SMC, and in vivo in vascular allografts. The aim of this study was to unveil the mechanism(s) of A20 mediated inhibition of IFNγ signaling. Adenovirus-mediated overexpression of A20 in SMC significantly decreased mRNA and protein levels of signal transducer and activator of transcription 1 (STAT1), the key mediator of IFNγ signaling, as a result of lower transcription. Moreover, overexpression of A20 in SMC also efficiently inhibited activating Y701 phosphorylation of STAT1, through a mechanism possibly implicating A20 binding to STAT1, as confirmed by co-immunoprecipitation. As expected, overexpression of A20 also inhibited NF-κB activation in SMC, which is required for full-blown IFNγ responses. Indeed, we confirmed that inhibition of NF-κB by overexpression of its inhibitor, IκBα also quenched upregulation of ISGs in SMC, albeit without down-regulating STAT1. Overall, our results identify A20 as a potent inhibitor of IFNγ signaling in SMC through several non-mutually exclusive mechanisms. This novel function of A20 in SMC further qualifies its atheroprotective properties and supports the pursuit of A20-based therapies for the cure of atherosclerotic vascular disease.

Peripheral Vascular Disease: Comparative Ultrastructure Of Veins, Valves And Arteries

1981 ◽  
Author(s):  
R L Reddick ◽  
T Griggs ◽  
A Romanenko ◽  
K M Brinkhous
Keyword(s):  
Smooth Muscle ◽  
Basement Membrane ◽  
Smooth Muscle Cells ◽  
Vascular Disease ◽  
Peripheral Vascular Disease ◽  
Muscle Cells ◽  
Cell Junctions ◽  
Ultrastructural Changes ◽  
Peripheral Vascular ◽  
Vein Wall

Ultrastructural changes in the coronary and cerebral arteries in thromboatherosclerosis have been well documented. Similar detailed studies in peripheral vascular disease (PVD) have not been described. Since PVD is frequently complicated by venous thrombosis, a comparative study of the arterial and venous pathology in patients with occlusive peripheral atherosclerosis was done. Anterior tibial artery and accompanying veins from seven cases were studied by light, transmission and scanning microscopy. Endothelial cell morphology was abnormal in all arteries. Cells contained lipid inclusions, prominent lysosomes, and cytoplasmic filaments were disorganized. Cell junctions were altered. Endothelial cells from both the vein wall and valve were morphologically normal. Basement membrane was reduplicated in both arteries and veins. In some arteries, the basement membrane was partially obscured by the atheromatous changes. Elastic lamina in veins, valves and arteries was fragmented. Smooth muscle cells of the arterial intima has significant morphologic alterations. The cells had a disorganized pattern and contained glycogen granules, lipid droplets and lysosomes in association with lipid. The filamentous pattern was disorganized and many cells appeared devoid of a basement membrane. Pinocytic vesicles were clearly evident. Smooth muscle cells comprising vein wall and valve were unremarkable. Collagen in arteries, veins and valves was haphazardly arranged with variation in fibrillar size. In some arteries, fibrous type collagen was found. Irregular, smudged collagen was present in all vessels examined. Calcification was noted in arteries only. These findings show a) a diversity of transmural alterations in arterial wall and b) ultrastructural changes in collagen in venous wall. The former is associated with thrombotic events, the latter not.

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