PMID- 11349007
OWN - NLM
STAT- MEDLINE
DCOM- 20010628
LR  - 20220129
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Linking)
VI  - 88
IP  - 9
DP  - 2001 May 11
TI  - Cardiac angiotensin II formation in the clinical course of heart failure and its 
      relationship with left ventricular function.
PG  - 961-8
AB  - In 76 patients with heart failure (HF) (New York Heart Association [NYHA] classes 
      I through IV) and in 15 control subjects, cardiac angiotensin II (Ang II) 
      generation and its relationship with left ventricular function were investigated 
      by measuring aorta-coronary sinus concentration gradients of endogenous 
      angiotensins and in a part of patients by studying (125)I-labeled Ang I kinetics. 
      Gene expression and cellular localization of the cardiac renin-angiotensin system 
      components, the density of AT(1) and AT(2) on membranes and isolated myocytes, 
      and the capacity of isolated myocytes for synthesizing the hypertrophying growth 
      factors insulin-like growth factor-I (IGF-I) and endothelin (ET)-1 were also 
      investigated on 22 HF explanted hearts (NYHA classes III and IV) and 7 nonfailing 
      (NF) donor hearts. Ang II generation increased with progression of HF, and 
      end-systolic wall stress was the only independent predictor of Ang II formation. 
      Angiotensinogen and angiotensin-converting enzyme mRNA levels were elevated in HF 
      hearts, whereas chymase levels were not, and mRNAs were almost exclusively 
      expressed on nonmyocyte cells. Ang II was immunohistochemically detectable both 
      on myocytes and interstitial cells. Binding studies showed that AT(1) density on 
      failing myocytes did not differ from that of NF myocytes, with preserved 
      AT(1)/AT(2) ratio. Conversely, AT(1) density was lower in failing membranes than 
      in NF ones. Ang II induced IGF-I and ET-1 synthesis by isolated NF myocytes, 
      whereas failing myocytes were unable to respond to Ang II stimulation. This study 
      demonstrates that (1) the clinical course of HF is associated with progressive 
      increase in cardiac Ang II formation, (2) AT(1) density does not change on 
      failing myocytes, and (3) failing myocytes are unable to synthesize IGF-I and 
      ET-1 in response to Ang II stimulation.
FAU - Serneri, G G
AU  - Serneri GG
AD  - Clinica Medica Generale e Cardiologia, University of Florence, Institute of 
      Thoracic and Cardiovascular Surgery, University of Siena, Italy.
FAU - Boddi, M
AU  - Boddi M
FAU - Cecioni, I
AU  - Cecioni I
FAU - Vanni, S
AU  - Vanni S
FAU - Coppo, M
AU  - Coppo M
FAU - Papa, M L
AU  - Papa ML
FAU - Bandinelli, B
AU  - Bandinelli B
FAU - Bertolozzi, I
AU  - Bertolozzi I
FAU - Polidori, G
AU  - Polidori G
FAU - Toscano, T
AU  - Toscano T
FAU - Maccherini, M
AU  - Maccherini M
FAU - Modesti, P A
AU  - Modesti PA
LA  - eng
GR  - 864/TI_/Telethon/Italy
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Endothelin-1)
RN  - 0 (Iodine Radioisotopes)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (Protein Precursors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 0 (Receptor, Angiotensin, Type 2)
RN  - 0 (Receptors, Angiotensin)
RN  - 11002-13-4 (Angiotensinogen)
RN  - 11128-99-7 (Angiotensin II)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 9041-90-1 (Angiotensin I)
RN  - EC 3.4.15.1 (Peptidyl-Dipeptidase A)
RN  - EC 3.4.21.- (Serine Endopeptidases)
RN  - EC 3.4.21.39 (Chymases)
SB  - IM
CIN - Circ Res. 2001 May 11;88(9):861-3. PMID: 11348994
MH  - Analysis of Variance
MH  - Angiotensin I/metabolism/pharmacology
MH  - Angiotensin II/*metabolism/pharmacology
MH  - Angiotensinogen/genetics
MH  - Cardiomyopathy, Dilated/genetics/metabolism/pathology
MH  - Cardiovascular Diseases/genetics/*metabolism/pathology
MH  - Chymases
MH  - Endothelin-1/genetics
MH  - Gene Expression
MH  - Gene Expression Regulation/drug effects
MH  - Heart Ventricles/cytology/metabolism/physiopathology
MH  - Immunohistochemistry
MH  - In Situ Hybridization
MH  - Insulin-Like Growth Factor I/genetics
MH  - Iodine Radioisotopes
MH  - Myocardial Ischemia/genetics/metabolism/pathology
MH  - Myocardium/*metabolism
MH  - Peptidyl-Dipeptidase A/genetics
MH  - Platelet-Derived Growth Factor/genetics
MH  - Protein Precursors/genetics
MH  - RNA, Messenger/drug effects/genetics/metabolism
MH  - Receptor, Angiotensin, Type 1
MH  - Receptor, Angiotensin, Type 2
MH  - Receptors, Angiotensin/genetics
MH  - Serine Endopeptidases/genetics
MH  - *Ventricular Function, Left
EDAT- 2001/05/23 10:00
MHDA- 2001/06/29 10:01
CRDT- 2001/05/23 10:00
PHST- 2001/05/23 10:00 [pubmed]
PHST- 2001/06/29 10:01 [medline]
PHST- 2001/05/23 10:00 [entrez]
AID - 10.1161/hh0901.089882 [doi]
PST - ppublish
SO  - Circ Res. 2001 May 11;88(9):961-8. doi: 10.1161/hh0901.089882.