In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 38, No. Suppl_1 ( 2018-05)
Abstract:
Background: Aortic atherosclerosis and dissection cause significant morbidity and mortality. Although atherosclerosis is associated with aortic dissection, points of interaction are unclear. Regulator-of-G-protein signaling 5 (RGS5) is still insufficiently characterized regarding its role in aortic atherosclerosis and dissection. Objectives: We investigated Rgs5-deficiencie’s effects on aortic atherosclerosis and dissection. Methods: ApoE -/- Rgs5 GFP/GFP double knockout mice (rraa, n=15) and WT littermates (RRaa, n=17) were fed a cholesterol-rich diet for 14weeks. Plaque size, plaque morphology (composition and a validated vulnerability score based on Stary criteria), macrophage phenotype and aortic dissection were evaluated. Results: rraa mice displayed more aortic dissections (5/15) compared to WT (0/17; p 〈 0.05 in Chi 2 -test). Surprisingly, rraa showed significantly smaller (rraa plaque size 190 657 μm 2 ± 93184 vs. control 398 279 μm 2 ± 153339) and less complicated plaques (5 of 15 mice with 〉 2 vulnerability features) compared to RRaa (14 of 15 with 〉 2 vulnerability features, p 〈 0.01). While relative areas of aSMA and lipids did not differ between genotypes, relative plaque areas positive for collagen and CD45 were increased in rraa (n=15/17, p 〈 0.01) compared to RRaa. Due to smaller plaque sizes were anti-inflammatory macrophages reduced and pro-inflammatory macrophages increased in absolute numbers (p 〈 0.05). Phenotyping of CD45 + -myeloid cells revealed increased proportions of macrophages staining positive for pro-inflammatory markers (Cd86/Cd45: 24.71 area% ± 3.75 for RRaa; 60.95 area% ± 5.909, for rraa and iNOS/Cd45: 37.22 area% ± 6.37, for RRaa; 73.99 area% ± 3.997 for rraa, p 〈 0.01), while anti-inflammatory markers (Cd163/Cd45 and Dectin/Cd45 double stainings) remained unchanged. Conclusions: rraa mice are more prone to aortic dissection despite smaller and less complex plaques with reduced anti-inflammatory but increased numbers of pro-inflammatory macrophages. We hypothesize that pro-inflammatory macrophage polarization along with evasion of anti-inflammatory macrophages in rraa mice could be causative for higher dissection numbers. Our data warrant further studies into the diverging pathomechanistic roles of Rgs5 in aortic dissection and atherosclerosis.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/atvb.38.suppl_1.416
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2018
detail.hit.zdb_id:
1494427-3
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