PMID- 29061718
OWN - NLM
STAT- MEDLINE
DCOM- 20171120
LR  - 20180113
IS  - 1524-4563 (Electronic)
IS  - 0194-911X (Linking)
VI  - 70
IP  - 6
DP  - 2017 Dec
TI  - Inhibition of Aneurysm Progression by Direct Renin Inhibition in a Rabbit Model.
PG  - 1201-1209
LID - 10.1161/HYPERTENSIONAHA.117.09815 [doi]
AB  - Angiotensin II is thought to participate in aneurysm formation, because of its 
      ability to induce and perpetuate inflammation in the aortic wall. Because 
      activation of renin is the first step of the renin-angiotensin system, renin 
      inhibition could inhibit all components of this system effectively. Therefore, we 
      examined the hypothesis that direct inhibition of renin activity could decrease 
      the expansion of aortic aneurysm using a rabbit model. Aortic dilatation was 
      induced by incubation with elastase around the rabbit abdominal aorta. Continuous 
      administration of a direct renin inhibitor, aliskiren, was started at 1 week 
      before incubation with elastase and continued for 5 weeks. Treatment with 
      aliskiren markedly inhibited tissue renin activation and resulted in a 
      significant reduction in angiotensin I and II production in the aneurysm wall. 
      Consequently, the inhibition of renin activity prevented the expansion of 
      experimental aortic aneurysm associated with preservation of the medial layer, 
      independent of its blood pressure-lowering effect. Administration of aliskiren 
      led to the inhibition of activation of NF-kappaB (nuclear factor-kappaB), AP-1 (activator 
      protein-1), and CREB (cAMP response element-binding protein), which are thought 
      to cooperatively regulate the inflammatory gene expression profile associated 
      with aneurysm formation. As a result, treatment with aliskiren inhibited 
      macrophage accumulation through suppression of MCP-1 (monocyte chemoattractant 
      protein-1) and CCL4 (C-C motif chemokine ligand 4) expression, and TNF-alpha (tumor 
      necrosis factor-alpha) production and activation of MMP-2 (matrix 
      metalloproteinase-2) and MMP-9 (matrix metalloproteinase-9) were also suppressed 
      in the aneurysm wall. In addition, inhibition of (pro)renin receptor elevation 
      was also observed after treatment with aliskiren. Direct inhibition of renin 
      activity using aliskiren prevented the progression of aortic aneurysm, suggesting 
      it as a therapeutic option to treat abdominal aortic aneurysm.
CI  - (c) 2017 American Heart Association, Inc.
FAU - Miyake, Takashi
AU  - Miyake T
AD  - From the Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka 
      University, Japan.
FAU - Miyake, Tetsuo
AU  - Miyake T
AD  - From the Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka 
      University, Japan.
FAU - Shimizu, Hideo
AU  - Shimizu H
AD  - From the Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka 
      University, Japan.
FAU - Morishita, Ryuichi
AU  - Morishita R
AD  - From the Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka 
      University, Japan. morishit@cgt.med.osaka-u.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20171023
PL  - United States
TA  - Hypertension
JT  - Hypertension (Dallas, Tex. : 1979)
JID - 7906255
RN  - 0 (Amides)
RN  - 0 (Fumarates)
RN  - 502FWN4Q32 (aliskiren)
RN  - 63231-63-0 (RNA)
RN  - EC 3.4.23.15 (Renin)
SB  - IM
MH  - Amides/*pharmacology
MH  - Animals
MH  - Aorta, Abdominal/*diagnostic imaging
MH  - Aortic Aneurysm, Abdominal/diagnosis/*drug therapy/genetics
MH  - Blotting, Western
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Fumarates/*pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Immunoenzyme Techniques
MH  - Immunohistochemistry
MH  - RNA/*genetics
MH  - Rabbits
MH  - Real-Time Polymerase Chain Reaction
MH  - Renin/*antagonists & inhibitors/genetics/metabolism
MH  - Renin-Angiotensin System/genetics
MH  - Ultrasonography
OTO - NOTNLM
OT  - aneurysm
OT  - angiotensin II
OT  - aortic aneurysm, abdominal
OT  - renin
OT  - renin-angiotensin system
EDAT- 2017/10/25 06:00
MHDA- 2017/11/29 06:00
CRDT- 2017/10/25 06:00
PHST- 2017/06/04 00:00 [received]
PHST- 2017/06/15 00:00 [revised]
PHST- 2017/09/26 00:00 [accepted]
PHST- 2017/10/25 06:00 [pubmed]
PHST- 2017/11/29 06:00 [medline]
PHST- 2017/10/25 06:00 [entrez]
AID - HYPERTENSIONAHA.117.09815 [pii]
AID - 10.1161/HYPERTENSIONAHA.117.09815 [doi]
PST - ppublish
SO  - Hypertension. 2017 Dec;70(6):1201-1209. doi: 10.1161/HYPERTENSIONAHA.117.09815. 
      Epub 2017 Oct 23.