PMID- 20110337
OWN - NLM
STAT- MEDLINE
DCOM- 20100920
LR  - 20231213
IS  - 1755-3245 (Electronic)
IS  - 0008-6363 (Print)
IS  - 0008-6363 (Linking)
VI  - 87
IP  - 1
DP  - 2010 Jul 1
TI  - An angiotensin II- and NF-kappaB-dependent mechanism increases connexin 43 in 
      murine arteries targeted by renin-dependent hypertension.
PG  - 166-76
LID - 10.1093/cvr/cvq031 [doi]
AB  - AIMS: Connexins (Cxs) play a role in the contractility of the aorta wall. We 
      investigated how connexins of the endothelial cells (ECs; Cx37, Cx40) and smooth 
      muscle cells (SMCs; Cx43, Cx45) of the aorta change during renin-dependent and 
      -independent hypertension. METHODS AND RESULTS: We subjected both wild-type (WT) 
      mice and mice lacking Cx40 (Cx40(-/-)), to either a two-kidney, one-clip 
      procedure or to N-nitro-l-arginine-methyl-ester treatment, which induce 
      renin-dependent and -independent hypertension, respectively. All hypertensive 
      mice featured a thickened aortic wall, increased levels of Cx37 and Cx45 in SMC, 
      and of Cx40 in EC (except in Cx40(-/-) mice). Cx43 was up-regulated, with no 
      effect on its S368 phosphorylation, only in the SMCs of renin-dependent models of 
      hypertension. Blockade of the renin-angiotensin system of Cx40(-/-) mice 
      normalized blood pressure and prevented both aortic thickening and Cx 
      alterations. Ex vivo exposure of WT aortas, carotids, and mesenteric arteries to 
      physiologically relevant levels of angiotensin II (AngII) increased the levels of 
      Cx43, but not of other Cx. In the aortic SMC line of A7r5 cells, AngII activated 
      kinase-dependent pathways and induced binding of the nuclear factor-kappa B 
      (NF-kappaB) to the Cx43 gene promoter, increasing Cx43 expression. CONCLUSION: In 
      both large and small arteries, hypertension differently regulates Cx expression 
      in SMC and EC layers. Cx43 is selectively increased in renin-dependent 
      hypertension via an AngII activation of the extracellular signal-regulated kinase 
      and NF-kappaB pathways.
FAU - Alonso, Florian
AU  - Alonso F
AD  - Service of Internal Medicine, Laboratory of Experimental Medicine 19-135S, 
      University Hospital, CHUV-1011 Lausanne, Switzerland.
FAU - Krattinger, Nathalie
AU  - Krattinger N
FAU - Mazzolai, Lucia
AU  - Mazzolai L
FAU - Simon, Alexander
AU  - Simon A
FAU - Waeber, Gerard
AU  - Waeber G
FAU - Meda, Paolo
AU  - Meda P
FAU - Haefliger, Jacques-Antoine
AU  - Haefliger JA
LA  - eng
GR  - HL64232/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 - 20100128
PL  - England
TA  - Cardiovasc Res
JT  - Cardiovascular research
JID - 0077427
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Connexin 43)
RN  - 0 (Connexins)
RN  - 0 (GJA1 protein, mouse)
RN  - 0 (NF-kappa B)
RN  - 11128-99-7 (Angiotensin II)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 3.4.23.15 (Renin)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
SB  - IM
MH  - Angiotensin II/*metabolism
MH  - Angiotensin II Type 1 Receptor Blockers/pharmacology
MH  - Angiotensin-Converting Enzyme Inhibitors/pharmacology
MH  - Animals
MH  - Antihypertensive Agents/pharmacology
MH  - Aorta/drug effects/*metabolism/physiopathology
MH  - Binding Sites
MH  - Blood Pressure
MH  - Carotid Arteries/metabolism/physiopathology
MH  - Cell Line
MH  - Connexin 43/genetics/*metabolism
MH  - Connexins/deficiency/genetics
MH  - Disease Models, Animal
MH  - Endothelial Cells/metabolism
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Genes, Reporter
MH  - Hypertension, Renovascular/drug therapy/etiology/*metabolism/physiopathology
MH  - Mesenteric Arteries/metabolism/physiopathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Myocytes, Smooth Muscle/metabolism
MH  - NF-kappa B/*metabolism
MH  - NG-Nitroarginine Methyl Ester
MH  - Nephrectomy
MH  - Phosphorylation
MH  - Promoter Regions, Genetic
MH  - Rats
MH  - Renin/*blood
MH  - Time Factors
MH  - Transfection
MH  - Up-Regulation
MH  - Gap Junction alpha-5 Protein
PMC - PMC2883896
EDAT- 2010/01/30 06:00
MHDA- 2010/09/21 06:00
PMCR- 2011/07/01
CRDT- 2010/01/30 06:00
PHST- 2010/01/30 06:00 [entrez]
PHST- 2010/01/30 06:00 [pubmed]
PHST- 2010/09/21 06:00 [medline]
PHST- 2011/07/01 00:00 [pmc-release]
AID - cvq031 [pii]
AID - 10.1093/cvr/cvq031 [doi]
PST - ppublish
SO  - Cardiovasc Res. 2010 Jul 1;87(1):166-76. doi: 10.1093/cvr/cvq031. Epub 2010 Jan 
      28.