PMID- 25752363
OWN - NLM
STAT- MEDLINE
DCOM- 20160615
LR  - 20181202
IS  - 1880-3873 (Electronic)
IS  - 1340-3478 (Print)
IS  - 1340-3478 (Linking)
VI  - 22
IP  - 8
DP  - 2015 Aug 26
TI  - Angiotensin Ⅱ Activates MCP-1 and Induces Cardiac Hypertrophy and Dysfunction via 
      Toll-like Receptor 4.
PG  - 833-44
LID - 10.5551/jat.27292 [doi]
AB  - AIM: Angiotensin Ⅱ(Ang Ⅱ) produces reactive oxygen species (ROS), thus 
      contributing to the development of cardiac hypertrophy and subsequent heart 
      failure, and stimulates the expression of monocyte chemoattractant protein-1 
      (MCP-1). In addition, Toll-like receptor 4 (TLR4) is involved in the upregulation 
      of MCP-1. In order to clarify whether TLR4 is involved in the onset of cardiac 
      dysfunction caused by Ang Ⅱ stimulation, we investigated the effects of TLR4 on 
      oxidative stress, the MCP-1 expression and cardiac dysfunction in mice with Ang 
      Ⅱ-induced hypertension. METHODS: TLR4-deficient (Tlr4(lps-d)) and wild-type (WT) 
      mice were randomized into groups treated with Ang Ⅱ, norepinephrine (NE) or a 
      subdepressor dose of the Ang Ⅱreceptor blocker irbesartan (IRB) and Ang Ⅱ for two 
      weeks. RESULTS: Ang Ⅱ and NE similarly increased systolic blood pressure in all 
      drug-treated groups compared to that observed in the control group among both WT 
      and Tlr4(lps-d) mice (p＜0.05). In the WT mice, Ang Ⅱ induced cardiac hypertrophy 
      as well as vascular remodeling and perivascular fibrosis of the intramyocardial 
      arteries and monocyte/macrophage infiltration in the heart (p＜0.05). Furthermore, 
      Ang Ⅱ treatment decreased the left ventricular diastolic function and resulted in 
      a greater left ventricular end-systolic dimension (p＜0.05) in addition to 
      producing a five-fold increase in the NADPH oxidase activity, ROS content and 
      MCP-1 expression (p＜0.05). In contrast, the Tlr4(lps-d) mice showed little 
      effects of Ang Ⅱ on these indices. In the WT mice, IRB treatment reversed these 
      changes compared to that seen in the mice treated with Ang Ⅱ alone. NE produced 
      little effect on any of the indices in either the WT or Tlr4(lps-d) mice. 
      CONCLUSIONS: TLR4 may be involved in the processes underlying the increased 
      oxidative stress, selectively activated MCP-1 expression and cardiac hypertrophy 
      and dysfunction seen in cases of Ang Ⅱ- induced hypertension.
FAU - Matsuda, Susumu
AU  - Matsuda S
AD  - Department of Medicine and Clinical Science, Yamaguchi University Graduate School 
      of Medicine.
FAU - Umemoto, Seiji
AU  - Umemoto S
FAU - Yoshimura, Koichi
AU  - Yoshimura K
FAU - Itoh, Shinichi
AU  - Itoh S
FAU - Murata, Tomoaki
AU  - Murata T
FAU - Fukai, Tohru
AU  - Fukai T
FAU - Matsuzaki, Masunori
AU  - Matsuzaki M
LA  - eng
GR  - I01 BX001232/BX/BLRD VA/United States
GR  - R01 HL070187/HL/NHLBI NIH HHS/United States
GR  - R01 HL 070187/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150305
PL  - Japan
TA  - J Atheroscler Thromb
JT  - Journal of atherosclerosis and thrombosis
JID - 9506298
RN  - 0 (Adrenergic alpha-Agonists)
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Tetrazoles)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Vasoconstrictor Agents)
RN  - 11128-99-7 (Angiotensin II)
RN  - J0E2756Z7N (Irbesartan)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Adrenergic alpha-Agonists/pharmacology
MH  - Angiotensin II/*pharmacology
MH  - Angiotensin II Type 1 Receptor Blockers/pharmacology
MH  - Animals
MH  - Biphenyl Compounds/pharmacology
MH  - Cardiomegaly/*etiology
MH  - Chemokine CCL2/*physiology
MH  - Hypertension/*etiology
MH  - Irbesartan
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Norepinephrine/pharmacology
MH  - Oxidative Stress/physiology
MH  - Tetrazoles/pharmacology
MH  - Toll-Like Receptor 4/*physiology
MH  - Vasoconstrictor Agents/*pharmacology
PMC - PMC5509415
MID - NIHMS877686
COIS- Conflicts of Interest The remaining authors declare no conflicts of interest.
EDAT- 2015/03/11 06:00
MHDA- 2016/06/16 06:00
PMCR- 2017/07/13
CRDT- 2015/03/11 06:00
PHST- 2015/03/11 06:00 [entrez]
PHST- 2015/03/11 06:00 [pubmed]
PHST- 2016/06/16 06:00 [medline]
PHST- 2017/07/13 00:00 [pmc-release]
AID - 10.5551/jat.27292 [doi]
PST - ppublish
SO  - J Atheroscler Thromb. 2015 Aug 26;22(8):833-44. doi: 10.5551/jat.27292. Epub 2015 
      Mar 5.