PMID- 31402541
OWN - NLM
STAT- MEDLINE
DCOM- 20200902
LR  - 20210110
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 23
IP  - 10
DP  - 2019 Oct
TI  - Anatomically specific reactive oxygen species production participates in Marfan 
      syndrome aneurysm formation.
PG  - 7000-7009
LID - 10.1111/jcmm.14587 [doi]
AB  - Marfan syndrome (MFS) is a connective tissue disorder that results in aortic root 
      aneurysm formation. Reactive oxygen species (ROS) seem to play a role in aortic 
      wall remodelling in MFS, although the mechanism remains unknown. MFS 
      Fbn1(C1039G/+) mouse root/ascending (AS) and descending (DES) aortic samples were 
      examined using DHE staining, lucigenin-enhanced chemiluminescence (LGCL), 
      Verhoeff's elastin-Van Gieson staining (elastin breakdown) and in situ zymography 
      for protease activity. Fbn1(C1039G/+) AS- or DES-derived smooth muscle cells 
      (SMC) were treated with anti-TGF-beta antibody, angiotensin II (AngII), anti-TGF-beta 
      antibody + AngII, or isotype control. ROS were detected during early aneurysm 
      formation in the Fbn1(C1039G/+) AS aorta, but absent in normal-sized DES aorta. 
      Fbn1(C1039G/+) mice treated with the unspecific NADPH oxidase inhibitor, apocynin 
      reduced AS aneurysm formation, with attenuated elastin fragmentation. In situ 
      zymography revealed apocynin treatment decreased protease activity. In vitro SMC 
      studies showed Fbn1(C1039G/+) -derived AS SMC had increased NADPH activity 
      compared to DES-derived SMC. AS SMC NADPH activity increased with AngII treatment 
      and appeared TGF-beta dependent. In conclusion, ROS play a role in MFS aneurysm 
      development and correspond anatomically with aneurysmal aortic segments. ROS 
      inhibition via apocynin treatment attenuates MFS aneurysm progression. AngII 
      enhances ROS production in MFS AS SMCs and is likely TGF-beta dependent.
CI  - (c) 2019 The Authors. Journal of Cellular and Molecular Medicine published by 
      Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
FAU - Emrich, Fabian
AU  - Emrich F
AD  - Department of Cardiothoracic Surgery, Stanford University, Stanford, California.
AD  - Department of Cardiothoracic Surgery, Leipzig University Heart Center, Leipzig, 
      Germany.
FAU - Penov, Kiril
AU  - Penov K
AD  - Department of Cardiothoracic Surgery, Stanford University, Stanford, California.
AD  - Department of Cardiothoracic Surgery, Leipzig University Heart Center, Leipzig, 
      Germany.
FAU - Arakawa, Mamoru
AU  - Arakawa M
AD  - Department of Cardiothoracic Surgery, Stanford University, Stanford, California.
AD  - Department of Cardiovascular Surgery, Jichi Medical University, Saitama, Japan.
FAU - Dhablania, Nathan
AU  - Dhablania N
AD  - Department of Cardiothoracic Surgery, Stanford University, Stanford, California.
FAU - Burdon, Grayson
AU  - Burdon G
AD  - Department of Cardiothoracic Surgery, Stanford University, Stanford, California.
FAU - Pedroza, Albert J
AU  - Pedroza AJ
AD  - Department of Cardiothoracic Surgery, Stanford University, Stanford, California.
FAU - Koyano, Tiffany K
AU  - Koyano TK
AD  - Department of Cardiothoracic Surgery, Stanford University, Stanford, California.
FAU - Kim, Young M
AU  - Kim YM
AD  - Department of Cardiovascular Medicine, Stanford University, Stanford, California.
FAU - Raaz, Uwe
AU  - Raaz U
AD  - Department of Cardiovascular Medicine, Stanford University, Stanford, California.
FAU - Connolly, Andrew J
AU  - Connolly AJ
AD  - Department of Pathology, Stanford University, Stanford, California.
FAU - Iosef, Cristiana
AU  - Iosef C
AUID- ORCID: 0000-0002-0535-8605
AD  - Department of Cardiothoracic Surgery, Stanford University, Stanford, California.
FAU - Fischbein, Michael P
AU  - Fischbein MP
AUID- ORCID: 0000-0002-0638-2025
AD  - Department of Cardiothoracic Surgery, Stanford University, Stanford, California.
LA  - eng
GR  - R01 AR066629/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20190811
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (Acetophenones)
RN  - 0 (Fibrillin-1)
RN  - 0 (Reactive Oxygen Species)
RN  - 11128-99-7 (Angiotensin II)
RN  - B6J7B9UDTR (acetovanillone)
RN  - EC 1.6.3.- (NADPH Oxidases)
SB  - IM
MH  - Acetophenones/pharmacology
MH  - Aneurysm/*complications/*metabolism
MH  - Angiotensin II
MH  - Animals
MH  - Aorta/metabolism/pathology
MH  - Disease Models, Animal
MH  - Fibrillin-1/deficiency/metabolism
MH  - Marfan Syndrome/*complications/*metabolism
MH  - Mice, Inbred C57BL
MH  - Myocytes, Smooth Muscle/drug effects/metabolism
MH  - NADPH Oxidases/metabolism
MH  - Reactive Oxygen Species/*metabolism
PMC - PMC6787454
OTO - NOTNLM
OT  - Marfan syndrome
OT  - aneurysm
OT  - reactive oxygen species
COIS- None.
EDAT- 2019/08/14 06:00
MHDA- 2020/09/04 06:00
PMCR- 2019/10/01
CRDT- 2019/08/13 06:00
PHST- 2019/06/06 00:00 [received]
PHST- 2019/07/15 00:00 [revised]
PHST- 2019/07/17 00:00 [accepted]
PHST- 2019/08/14 06:00 [pubmed]
PHST- 2020/09/04 06:00 [medline]
PHST- 2019/08/13 06:00 [entrez]
PHST- 2019/10/01 00:00 [pmc-release]
AID - JCMM14587 [pii]
AID - 10.1111/jcmm.14587 [doi]
PST - ppublish
SO  - J Cell Mol Med. 2019 Oct;23(10):7000-7009. doi: 10.1111/jcmm.14587. Epub 2019 Aug 
      11.