CLINICAL STUDY
Activation of cardiac renin-angiotensin system in unstable angina
Gian Gastone Neri Serneri, MD*,
Maria Boddi, MD, PhD*,
Loredana Poggesi, MD*,
Ignazio Simonetti, MD*,
Mirella Coppo, BSc*,
Maria Letizia Papa, BSc*,
Gian Franco Lisi, MD ,
Massimo Maccherini, MD,
Roberto Becherini, MD*,
Andrea Boncompagni, MD*,
Thomas Toscano, MD and
Pietro Amedeo Modesti, MD, PhD*
* Clinica Medica Generale e Cardiologia, University of Florence, Florence, Italy
Institute of Thoracic and Cardiovascular Surgery, University of Siena, Siena, Italy
Manuscript received December 6, 2000;
revised manuscript received March 29, 2001,
accepted April 5, 2001.
Reprint requests and correspondence: Dr. Gian Gastone Neri Serneri, Clinica Medica Generale e Cardiologia, University of Florence, Viale Morgagni 85 50134, Florence, Italy
gg.neriserneri{at}dfc.unifi.it
OBJECTIVES
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.
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Abbreviations and Acronyms
| | ACE | = angiotensin-converting enzyme | | AGTN | = angiotensinogen | | Ang | = angiotensin | | AT1 | = angiotensin II type 1 receptor | | AT2 | = angiotensin II type 2 receptor | | CBF | = coronary blood flow | | CVR | = coronary vascular resistance | | GAPDH | = glyceraldeyde-3-phosphate dehydrogenase | | mRNA | = messenger RNA | | PRA | = plasma renin activity | | RAS | = renin-angiotensin system | | RT-PCR | = reverse transcriptase-polymerase chain reaction | | SA | = stable effort angina | | UA | = unstable angina |
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