Effects of ultraviolet light in vascular cells in vitro and in intact atherosclerotic explants: potential role of apoptosis in vascular biology

1996 ◽  
Vol 74 (3) ◽  
pp. 333-345 ◽  
Author(s):  
Angel López-Candales ◽  
Michael J. Scott ◽  
Samuel A. Wickline ◽  
Dennis R. Holmes ◽  
Robert W. Thompson

Complex cell-to-cell interactions are known to participate during vascular injury and remodeling, resulting in smooth muscle cell proliferation. Mechanical interventions have yielded little benefit in limiting this process and several site-specific genetic therapies are not yet clinically available. The aim of this study was to delineate the effect of very short wavelength ultraviolet (UVC) light therapy on the viability of macrophage and smooth muscle cells. Vascular cells were both treated in vitro and in intact explanted atherosclerotic aortic segments ex vivo with UVC light. Brief exposure to short wavelength UVC light in the absence of photosensitizers elicited a differential temporal and functional response among treated cells. However, dramatic reduction in both cellular viability and proliferative capacity with eventual cell demise was observed in all UVC-treated cells. Flow cytometry and immunohistochemical analyses revealed the presence of extensive DNA fragmentation, suggestive of apoptosis as a predominant pathway of cell death in these cells exposed to UVC light. We hypothesize that selective induction of apoptosis, in contrast to necrosis, with UVC light may represent a beneficial approach to interdict the complex biologic cascade of messengers that participate in the restenotic response to vascular injury.Key words: apoptosis, macrophage, smooth muscle cell, atherosclerotic aorta, New Zealand White rabbit.

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Matthew J Butcher ◽  
Tayab C Waseem ◽  
Elena V Galkina

Atherosclerosis is characterized by frequent communication between infiltrating leukocytes and vascular cells, through chemokine and cytokine networks. IL-17 cytokine family members, including IL-17C, are detectable within atherosclerotic plaques, however the potential involvement of these cytokines have not been examined. Thus we sought to investigate the role of IL-17C in atherosclerosis. The expression of IL-17 cytokines was profiled within atherosclerotic Apoe -/- aortas and Il17c expression was elevated. Flow cytometry experiments revealed a major population of aortic IL-17C-producing smooth muscle cells. To determine the role of IL-17C in atherosclerosis, we generated Il17c -/- Apoe -/- mice and compared atherosclerotic lesions between western diet-fed Apoe -/- and Il17c -/- Apoe -/- mice. Atherosclerotic lesion and collagen content was diminished within WD-fed Il17c -/- Apoe -/- aortas and aortic roots in comparison to Apoe -/- controls, and IL-17C treated Apoe -/- aortas up-regulated Col1A1 expression ex vivo . Flow cytometric analysis of Il17c -/- Apoe -/- aortas revealed a proportional reduction in aortic leukocytes, macrophages, neutrophils, T cells, Th1, and T regulatory cells, without corresponding changes in the peripheral immune composition. Examination of aortic IL-17A + TCRγδ T cells and Th17 cells demonstrated a stark reduction in the percentage and number of these subsets within Il17c -/- Apoe -/- mice versus Apoe -/- controls. Explanted 12 week WD Apoe -/- aortas treated with IL-17C resulted in the induction of multiple vascular chemokines and cytokines, and short-term homing experiments revealed diminished recruitment of Th17 cells to the aorta of Il17c -/- Apoe -/- recipients. Smooth muscle cell-derived IL-17C plays a pro-atherogenic role by supporting the recruitment of Th17 cells to atherosclerotic lesions.


1998 ◽  
Vol 83 (3) ◽  
pp. 241-251 ◽  
Author(s):  
Karen O Yee ◽  
Michael M. Rooney ◽  
Cecilia M. Giachelli ◽  
Susan T. Lord ◽  
Stephen M. Schwartz

1997 ◽  
Vol 78 (02) ◽  
pp. 880-886 ◽  
Author(s):  
Monique J Wijnberg ◽  
Paul H A Quax ◽  
Nancy M E Nieuwenbroek ◽  
Jan H Verheijen

SummaryThe plasminogen activation system is thought to be important in cell migration processes. A role for this system during smooth muscle cell migration after vascular injury has been suggested from several animal studies. However, not much is known about its involvement in human vascular remodelling. We studied the involvement of the plasminogen activation system in human smooth muscle cell migration in more detail using an in vitro wound assay and a matrix invasion assay. Inhibition of plasmin activity or inhibition of urokinase-type plasminogen activator (u-PA) activity resulted in approximately 40% reduction of migration after 24 h in the wound assay and an even stronger reduction (70-80%) in the matrix invasion assay. Migration of smooth muscle cells in the presence of inhibitory antibodies against tissue-type plasminogen activator (t-PA) was not significantly reduced after 24 h, but after 48 h a 30% reduction of migration was observed, whereas in the matrix invasion assay a 50% reduction in invasion was observed already after 24 h. Prevention of the interaction of u-PA with cell surface receptors by addition of soluble u-PA receptor or α2-macroglobulin receptor associated protein (RAP) to the culture medium, resulted in a similar inhibition of migration and invasion. From these results it can be concluded that both u-PA and t-PA mediated plasminogen activation can contribute to in vitro human smooth muscle cell migration and invasion. Furthermore, the interaction between u-PA and its cell surface receptor appears also to be involved in this migration and invasion process. The inhibitory effects on migration and invasion by the addition of RAP suggests an involvement of a RAP sensitive receptor of the LDL receptor family, possibly the LDL-receptor related protein (LRP) and/or the VLDL receptor.


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