Winning Abstract of Breaking News ISCOMS 2017

Title: Endogenous inhibitor of inflammation Del-1 protects from Angiotensin II induced hypertension
and cardiovascular remodeling

Author: Theresa Failer

Field of research: Vascular medicine

Hypertension is a global health concern and the major risk factor for cardiovascular diseases. There is
a strong evidence that inflammation contributes to development of hypertension. Chronic activation of
renin-angiotensin-system and particularly angiotensin II (ANGII) promotes vascular inflammation
leading to vascular stiffness and ultimately to hypertension. Interleukin 17 (IL-17) is an effector cytokine
mediating adverse vascular effects of ANGII. Recently, we identified Del-1- an extracellular matrix protein
expressed by endothelial cells, which is a potent inhibitor of IL-17 production.
We tested the hypothesis that Del-1 protects from ANGII mediated adverse aortic remodeling and
development of hypertension via inhibition of IL-17 production.

Material & methods
Hypothesis was tested in endothelial specific Del-1 overexpressing (Del-1 TG) and wild type (WT) mice, which
were infused with ANGII (0.7 mg/kg/day) for 4 weeks. Endothelial function was tested indirectly by assessing
endothelium-dependent vasorelaxation with acetylcholine in Mulvany myograph. Sirius red staining, hematoxylin
eosin staining and Van Gieson Elastin staining were used to evaluate fibrosis, medial hypertrophy and content of
Elastin in the aorta, respectively. IL-17 was detected with immunostaining. The amount of hematopoietic cells in
aorta and adventitia was assessed with flow cytometry

Results show that Del-1 TG mice developed significantly (P<0.01) less aortic fibrosis and medial hypertrophy with
significantly (P<0.01) improved endothelial function compared to WT. While WT mice lost ~50% of aortic elastin,
in aorta of Del-1 Tg mice aortic elastin was preserved. This was associated with significantly (P<0.01) less activity
of MMP-2 in aorta of Del-1 mice. There was markedly less infiltration of CD8 and CD4 lymphocytes in aorta of
Del-1 mice compared to WT.  Immunostainings demonstrated less IL-17 in aortas of Del-1 Tg mice in contrast
with WT. Systolic blood pressure was significantly (P<0.01) lower in Del-1 Tg than in WT. We found less cardiac
hypertrophy, interstitial and coronary fibrosis in the myocardium in Del-1 Tg mice compared to WT.

Our study reveals Del-1 as a protective factor in development of ANGII mediated adverse cardiovascular remodeling
and hypertension via inhibition of IL-17 production. Del-1 is a potential therapeutic agent in prevention of cardiovascular
remodeling and hypertension.