Download 2015 department of medicine research day

2015 DEPARTMENT OF MEDICINE RESEARCH DAY
Title of Poster: Ambient Ultrafine Particles Impair Vascular Repair via Notch Signaling
Presenter: Rongsong Li
Division: Cardiology
X Faculty ☐Fellow ☐Resident ☐Post-doc Research Fellow ☐Graduate Student ☐Medical Student ☐Other
Principal Investigator/Mentor: Tzung Hsiai
Kaboodrangidaem
Co-Investigators: Kyung Baek, Tyler Bebee, Amir
Thematic Poster Category: Genetic Diseases, Gene-Environment Interactions, Gene Therapy
Abstract
Introduction: Epidemiologic studies have consistently supported the link of air pollution with
cardiopulmonary diseases. Ultrafine particles (UFP), which are less than 0.1 micrometer in diameter,
are the major component of particular matter (PM) in air pollutant with higher oxidant capacity and
pro-inflammatory potential and more harmful to human health than larger PM. We and others have
previous shown UFP induce oxidative stress and endothelial cell dysfunction to promote
atherosclerosis. In this study, we tested the hypothesis that UFPs impair vascular repair via
modulation of notch signaling in zebrafish tail amputation model.
Methods and Results: Vascular repair was assessed using the Tg(flk-1:EGFP) transgenic zebrafish.
Tail amputation was performed three days post fertilization (dpf). Post-amputation fishes were treated
with or without 25 µg/ml UFP in E3 solution. UFP induced abnormal vascular repair in the zebrafish
model (n=16 out of 20) compared to control (n=4 out of 20). Abnormalities included incomplete
repair between the dorsal aorta and dorsal longitudinal anastomotic vessel and irregular sprouting.
Accompanied with abnormal vascular repair, the expression of Notch signaling related genes such as
notch receptor Notch1b, notch target gene Hey2, and notch ligand JAG1 and JAG2 were downregulated. Treatment of embryos with Adam10-inhibitor to decrease notch signaling recapitulated
similar impaired vascular regeneration and the down-regulation of Notch signaling genes. Human
aortic endothelial cells (HAEC) treated with UFP inhibited Notch signaling as demonstrated by Notch
reporter assay and the expression of Notch signaling related genes.
Conclusions: The results indicate that UFP induces aberrant vessel repair associated with inhibition
of Notch signaling. Rescuing vessel repair by over-expressing notch signaling in our zebrafish vascular
repair model will open avenues for notch-based intervention to mitigate the effects of UFP on vascular
function.
Acknowledgements: This study was supported by NIH R01HL083015, R01HL111437, and
R01HL129727.