Abstract 584: Smooth Muscle Cell-derived IL-17C Plays an Atherogenic Role via the Recruitment of Pro-inflammatory IL-17A
            +
            T Cells to the Aorta

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.

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

Biochemistry and Cell Biology ◽

10.1139/o96-036 ◽

1996 ◽

Vol 74 (3) ◽

pp. 333-345 ◽

Cited By ~ 14

Author(s):

Angel López-Candales ◽

Michael J. Scott ◽

Samuel A. Wickline ◽

Dennis R. Holmes ◽

Robert W. Thompson

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cell ◽

Muscle Cell ◽

Short Wavelength ◽

Ex Vivo ◽

Zealand White Rabbit ◽

Light Therapy ◽

Vascular Cells

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.

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Abstract 552: IL-17C-Producing Aortic Smooth Muscle Cells Play a Pro-Atherogenic Role Via the Recruitment of Inflammatory IL-17A+ T Cells

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.35.suppl_1.552 ◽

2015 ◽

Vol 35 (suppl_1) ◽

Author(s):

Matthew J Butcher ◽

Elena V Galkina

Keyword(s):

T Cells ◽

Smooth Muscle ◽

Smooth Muscle Cells ◽

Th17 Cells ◽

Muscle Cells ◽

Western Diet ◽

Atherosclerotic Lesions ◽

Flow Cytometric ◽

Cytokine Networks

Atherosclerosis is characterized by frequent communication between infiltrating leukocytes and vascular cells, through chemokine and cytokine networks. Various IL-17 cytokine family members are detected within atherosclerotic plaques; however the involvement of IL-17B-IL-17E has not been thoroughly examined. Aortic IL-17 cytokines were initially profiled and Il17a, Il17f, and Il17c mRNA expression was found to be elevated in Apoe-/- aortas in comparison to C57Bl6 controls. To determine the cellular sources of aortic IL-17C, aortic IL-17C-producing cells were phenotyped by flow cytometry. Surprisingly, these experiments revealed a major population of IL-17C-producing smooth muscle cells within Apoe-/- versus C57Bl6 aortas. To determine the role of IL-17C in atherosclerosis, we generated Il17c-/-Apoe-/- mice and compared 12 week western diet-fed Apoe-/- and Il17c-/-Apoe-/- mice. Atherosclerotic lesions were reduced by 42±2.6% in WD-fed Il17c-/-Apoe-/- aortas in comparison to Apoe-/- controls. Flow cytometric analyses of Il17c-/-Apoe-/- mice revealed a reduction in the number of aortic leukocytes, macrophages, neutrophils, and T cells, which corresponded with smaller atherosclerotic lesions (40±5%). However, the percentage and number of aortic IL-17A+ TCRγδ T cells and Th17 cells were disproportionately reduced within Il17c-/-Apoe-/- aortas (70±5%). We hypothesized that IL-17C might support the recruitment of Th17 cells to the aorta. To study comparative Th17 migration, Apoe-/- T cells were transferred to western diet-fed Il17c-/-Apoe-/- and Apoe-/- recipients and examined for Th1 and Th17 migration 48 hours post transfer. We found diminished accumulation of Th17, but not Th1 T cells, in the aortas of Il17c-/-Apoe-/- versus Apoe-/- recipients. Thus smooth muscle cell-derived IL-17C plays a pro-atherogenic role by supporting the recruitment of Th17 cells to atherosclerotic lesions.

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