title: Activation of cardiac renin-angiotensin system in unstable angina.
abstract: OBJECTIVE
  The aim of this study was to investigate the activity of the cardiac renin-angiotensin system (RAS) in unstable angina (UA).
  
  
  BACKGROUND
  Angiotensin (Ang) II locally produced by continuously operating cardiac RAS may affect the pathophysiology of UA.
  
  
  METHODS
  In 35 patients with UA, 32 with stable effort angina (SA) and 21 with atypical chest pain (controls), cardiac RAS was investigated during coronary angiography after five days of Holter monitoring by combining the measurement of aorta-coronary sinus gradient for Ang I and Ang II with the kinetics study of 125I-Ang I. Messenger RNAs (mRNA) for all the components of RAS were also quantified with the reverse transcriptase-polymerase chain reaction (RT-PCR) and localized by in situ hybridization in myocardial biopsy specimens from patients who underwent aorta-coronary bypass surgery.
  
  
  RESULTS
  Cardiac Ang II generation was higher in patients with UA than it was in patients with SA or in controls (p < 0.001) due to increased de novo cardiac Ang I formation and its enhanced fractional conversion rate to Ang II. Messenger RNA levels for angiotensinogen (AGTN), angiotensin-converting enzyme (ACE) and Ang II type 1 (AT1) subtype receptors were higher in patients with UA (p < 0.01) than they were in patients with SA or in control hearts. Messenger RNAs for AGTN and ACE were almost exclusively expressed on endothelial and interstitial cells. Angiotensin II formation was correlated with ischemia burden (p < 0.001). However, the amount of Ang II formed and the expression levels of mRNAs for AGTN, ACE and AT1 were not related to the time that had elapsed since the last anginal attack.
  
  
  CONCLUSIONS
  In patients with UA, cardiac RAS is activated, resulting in increased Ang II formation. Myocardial ischemia is essential for RAS activation, but it is unlikely to be a direct and immediate cause of RAS activation.
authors.affiliation: Clinica Medica Generale e Cardiologia, University of Florence, Italy. gg.neriserneri@dfc.unifi.it
authors.forename: G G
authors.initials: GG
authors.lastname: Neri Serneri
authors.forename: M
authors.initials: M
authors.lastname: Boddi
authors.forename: L
authors.initials: L
authors.lastname: Poggesi
authors.forename: I
authors.initials: I
authors.lastname: Simonetti
authors.forename: M
authors.initials: M
authors.lastname: Coppo
authors.forename: M L
authors.initials: ML
authors.lastname: Papa
authors.forename: G F
authors.initials: GF
authors.lastname: Lisi
authors.forename: M
authors.initials: M
authors.lastname: Maccherini
authors.forename: R
authors.initials: R
authors.lastname: Becherini
authors.forename: A
authors.initials: A
authors.lastname: Boncompagni
authors.forename: T
authors.initials: T
authors.lastname: Toscano
authors.forename: P A
authors.initials: PA
authors.lastname: Modesti
mesh_terms: D000368:Aged; D000789:Angina, Unstable / Q000503:physiopathology*; D000804:Angiotensin II / Q000502:physiology; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology; D012333:RNA, Messenger / Q000032:analysis; D011945:Receptors, Angiotensin / Q000502:physiology; D012084:Renin-Angiotensin System; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D000804:Angiotensin II