Single exposure to radiation produces early anti-angiogenic effects in mouse aorta.
Radiation exposure can increase the risk for many non-malignant physiological complications, including cardiovascular disease. We have previously demonstrated that ionizing radiation can induce endothelial dysfunction, which contributes to increased vascular stiffness. In this study, we demonstrate that gamma radiation exposure reduced endothelial cell viability or proliferative capacity using an in vitro aortic angiogenesis assay. Segments of mouse aorta were embedded in a Matrigel-media matrix 1 day after mice received whole-body gamma irradiation between 0 and 20 Gy. Using three-dimensional phase contrast microscopy, we quantified cellular outgrowth from the aorta. Through fluorescent imaging of embedded aortas from Tie2GFP transgenic mice, we determined that the cellular outgrowth is primarily of endothelial cell origin. Significantly less endothelial cell outgrowth was observed in aortas of mice receiving radiation of 5, 10, and 20 Gy radiation, suggesting radiation-induced endothelial injury. Following 0.5 and 1 Gy doses of whole-body irradiation, reduced outgrowth was still detected. Furthermore, outgrowth was not affected by the location of the aortic segments excised along the descending aorta. In conclusion, a single exposure to gamma radiation significantly reduces endothelial cell outgrowth in a dose-dependent manner. Consequently, radiation exposure may inhibit re-endothelialization or angiogenesis after a vascular injury, which would impede vascular recovery.
Soucy
Kevin G
KG
Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
Attarzadeh
David O
DO
Ramachandran
Raghav
R
Soucy
Patricia A
PA
Romer
Lewis H
LH
Shoukas
Artin A
AA
Berkowitz
Dan E
DE
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects*; D001013:Aorta, Thoracic / Q000166:cytology / Q000502:physiology / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D042783:Endothelial Cells / Q000166:cytology / Q000528:radiation effects; D005720:Gamma Rays; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000528:radiation effects*; D014916:Whole-Body Irradiation
Methods Enzymol. 2008;443:119-36
18772014
Nitric Oxide. 1997 Aug;1(4):275-81
9441899
J Clin Oncol. 2002 Jan 1;20(1):282-8
11773180
Radiother Oncol. 2002 May;63(2):129-45
12063002
Circulation. 1999 Aug 10;100(6):635-41
10441101
Radiat Res. 2001 Feb;155(2):353-9
11175671
Radiat Res. 1999 Jul;152(1):14-28
10381837
Radiat Res. 1995 May;142(2):117-32
7724726
Radiother Oncol. 1999 Aug;52(2):157-64
10577701
Microsc Res Tech. 2003 Jan 1;60(1):107-14
12500267
Int J Radiat Oncol Biol Phys. 2001 Jul 15;50(4):1033-9
11429231
Radiat Environ Biophys. 2007 Jun;46(2):179-86
17256177
Radiol Clin North Am. 1971 Dec;9(3):511-31
5001977
Science. 1997 Feb 14;275(5302):964-7
9020076
JAMA. 1993 Oct 27;270(16):1949-55
8411552
Int J Radiat Oncol Biol Phys. 1985 Apr;11(4):801-8
3980275
Am J Pathol. 2004 Jun;164(6):1887-92
15161625
Radiat Res. 1987 Apr;110(1):118-28
3562789
Lancet. 2000 May 20;355(9217):1757-70
10832826
Radiat Res. 2001 Sep;156(3):232-40
11500132
J Immunol. 2008 Oct 15;181(8):5711-9
18832730
FASEB J. 2008 Apr;22(4):1226-36
18032636
Radiat Res. 1995 Oct;144(1):64-72
7568773
Nature. 2005 Dec 15;438(7070):932-6
16355210
Clin Exp Pharmacol Physiol. 2001 Oct;28(10):816-21
11553021
Circ Res. 2004 Aug 20;95(4):343-53
15321944
Biochem Biophys Res Commun. 2008 Apr 4;368(2):364-7
18237547
Blood. 1998 Aug 1;92(3):765-9
9680342
J Natl Cancer Inst. 2009 Jul 1;101(13):928-37
19535773
Cancer Res. 2003 Mar 1;63(5):1012-9
12615716
Lancet Oncol. 2006 May;7(5):431-5
16648048
J Am Coll Cardiol. 2008 Feb 12;51(6):660-8
18261686
Radiat Res. 2003 Oct;160(4):381-407
12968934
Br J Pharmacol. 1998 Feb;123(4):653-60
9517384