PMID- 17204292
OWN - NLM
STAT- MEDLINE
DCOM- 20070326
LR  - 20151119
IS  - 0024-3205 (Print)
IS  - 0024-3205 (Linking)
VI  - 80
IP  - 11
DP  - 2007 Feb 20
TI  - Endogenous angiotensin II enhances atherogenesis in apoprotein E-deficient mice 
      with renovascular hypertension through activation of vascular smooth muscle 
      cells.
PG  - 1057-63
AB  - Renovascular hypertension is one of the most important risk factors in the 
      development of atherosclerosis. However, very little is known about the role of 
      angiotensin II (AII), a key regulator of blood pressure homeostasis, on 
      renovascular hypertension-associated atherogenesis. To study a possible role of 
      AII on atherogenesis, we generated apoE-deficient hypertensive mice with either 
      normal or increased AII production by applying 1-kidney, 1-clip (1K1C) or 
      2-kidney, 1-clip (2K1C) operation, respectively. Hypertension was successfully 
      achieved in both mice groups, and was persistent for 8 weeks. Atherosclerosis 
      quantification showed a marked increase in lesion area in aortic sinus of 2K1C 
      mice as compared with 1K1C mice, suggesting a potential role of endogenous AII on 
      atherogenesis. In the immunohistochemical analysis, induction of renovascular 
      hypertension with 2K1C for 8 weeks led to an enhanced accumulation of macrophages 
      in the aortic sinus, which was accompanied by a parallel increase in scavenger 
      receptor A (SRA) expression on the macrophages. In in vitro experiments, although 
      treatment of cells with increasing concentrations of AII (0.1 to 10 microM) 
      affects neither SRA expression nor oxLDL uptake by macrophages, conditioned media 
      (CM) derived from AII-stimulated vascular smooth muscle cells (VSMC) increased 
      macrophage uptake of oxLDL in association with an enhanced expression of SRA on 
      the macrophages. These findings suggest that the increased generation of AII in 
      renovascular hypertension may initiate and promote atherosclerosis by activation 
      of VSMC.
FAU - Heo, Hye Jin
AU  - Heo HJ
AD  - Department of Pharmacology, College of Medicine and Medical Research Center for 
      Ischemic Tissue Regeneration, Pusan National University, Seo-Gu, Busan, Korea.
FAU - Yun, Mi Ran
AU  - Yun MR
FAU - Jung, Keun Hwa
AU  - Jung KH
FAU - Lee, Ji Young
AU  - Lee JY
FAU - Park, Ji Young
AU  - Park JY
FAU - Lee, Seung Jin
AU  - Lee SJ
FAU - Bae, Sun Sik
AU  - Bae SS
FAU - Lee, Won Suk
AU  - Lee WS
FAU - Kim, Chi Dae
AU  - Kim CD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20061215
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Apolipoproteins E)
RN  - 0 (Biomarkers)
RN  - 0 (Culture Media, Conditioned)
RN  - 11128-99-7 (Angiotensin II)
SB  - IM
MH  - Angiotensin II/*metabolism/pharmacology
MH  - Animals
MH  - Apolipoproteins E/*deficiency/genetics
MH  - Atherosclerosis/genetics/*metabolism/pathology
MH  - Biomarkers/metabolism
MH  - Cell Line
MH  - Culture Media, Conditioned/pharmacology
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Fluorescent Antibody Technique, Indirect
MH  - Foam Cells/drug effects/metabolism/pathology
MH  - Gene Silencing
MH  - Hypertension, Renovascular/genetics/*metabolism/pathology
MH  - Image Processing, Computer-Assisted
MH  - Immunoenzyme Techniques
MH  - Mice
MH  - Mice, Knockout
MH  - Muscle, Smooth, Vascular/*metabolism/pathology
MH  - Sinus of Valsalva/metabolism/pathology
EDAT- 2007/01/06 09:00
MHDA- 2007/03/27 09:00
CRDT- 2007/01/06 09:00
PHST- 2006/07/31 00:00 [received]
PHST- 2006/11/01 00:00 [revised]
PHST- 2006/11/24 00:00 [accepted]
PHST- 2007/01/06 09:00 [pubmed]
PHST- 2007/03/27 09:00 [medline]
PHST- 2007/01/06 09:00 [entrez]
AID - S0024-3205(06)00941-6 [pii]
AID - 10.1016/j.lfs.2006.11.046 [doi]
PST - ppublish
SO  - Life Sci. 2007 Feb 20;80(11):1057-63. doi: 10.1016/j.lfs.2006.11.046. Epub 2006 
      Dec 15.