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European Heart Journal Advance Access originally published online on August 31, 2007
European Heart Journal 2007 28(22):2785-2791; doi:10.1093/eurheartj/ehm370
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© Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2007. For permissions please email: journals.permissions@oxfordjournals.org

Upregulation of myocardial Annexin A5 in hypertensive heart disease: association with systolic dysfunction

Susana Ravassa1, Arantxa González1, Begoña López1, Javier Beaumont1, Ramón Querejeta2, Mariano Larman3 and Javier Díez1,4,*

1 Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain
2 Division of Cardiology, Donostia University Hospital, San Sebastián, Spain
3 Division of Hemodynamics, Guipuzcoa Polyclinics, San Sebastián, Spain
4 Department of Cardiology and Cardiovascular Surgery, University Clinic, University of Navarra, Pamplona, Spain

Received 23 March 2007; revised 3 July 2007; accepted 3 August 2007; online publish-ahead-of-print 31 August 2007.

* Corresponding author. Tel: +34 948 194700; fax: +34 948 194716. E-mail address: jadimar{at}unav.es

See page 2695 for the editorial comment on this article (doi:10.1093/eurheartj/ehm452)

Aims: To investigate whether Annexin A5 (AnxA5) is related to hypertensive heart disease (HHD) and whether this relation is dependent of apoptosis.

Methods and results: Hypertensives without cardiac abnormalities (stage A), with left ventricular hypertrophy (LVH) (stage B), and with LVH and clinical manifestations of chronic HF (stage C), were studied. AnxA5 was quantified in endomyocardial biopsies by real time RT–PCR, Western blot, and immunohistochemistry, and apoptosis by DNA fragmentation, caspase-3 activation, and PARP and Bax/Bcl-2 ratios. Plasma AnxA5 was measured by ELISA in samples from the coronary sinus and the antecubital vein. Although AnxA5 mRNA did not change, myocardial and plasma AnxA5 were increased in hypertensives stages B and C compared with normotensives and hypertensives stage A. Myocardial AnxA5 was inversely correlated with parameters assessing systolic function in all hypertensives, this association being independent of apoptosis. Myocardial AnxA5 was directly correlated with plasma AnxA5. Plasma AnxA5 was inversely correlated with systolic function in all hypertensives.

Conclusion: This cross-sectional study shows that myocardial AnxA5 upregulation is associated with HHD and impairment of systolic function in hypertensive patients, this association being independent of apoptosis. Plasma AnxA5 can be a marker of myocardial AnxA5 upregulation and systolic dysfunction in patients with HHD.

Key Words: Annexin A5 • Apoptosis • Heart failure • Hypertension


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