Submitted on December 19, 2005
Accepted on June 8, 2006
ACE2 Gene Transfer Attenuates Hypertension Linked Pathophysiological Changes in the SHR
Carlos Diez-Freire1, Jorge Vazquez1, Maria F Correa de Adjounian1, Merari FR Ferrari1, Lihui Yuan1, Xeve Silver1, Raquel Torres1, and Mohan K. Raizada1*
1 Physiology and Functional Genomics, University of Florida, Gainesville, Florida, United States
* To whom correspondence should be addressed. E-mail: mraizada{at}phys.med.ufl.edu.
Recently discovered angiotensin converting enzyme (ACE2) is an important therapeutic target in the control of cardiovascular diseases as a result of its proposed central role in the control of angiotensin peptides. Thus, our objective in the present study was to determine if ACE2 gene transfer could decrease high blood pressure (BP) and would improve cardiac dysfunctions induced by hypertension in the SHR model. Five-day old SHR and normotensive WKY rats received a single intra cardiac bolus injection of lentiviral vector containing either murine ACE2 (ACE2) or control EGFP genes. Systolic BP, cardiac functions and perivascular fibrosis were evaluated four months following ACE2 gene transduction. ACE2 gene transfer resulted in a significant attenuation of high BP in the SHR (149+2mmHg in lenti-ACE2 vs. 180+9 mmHg in lenti-EGFP p<0.01). In contrast, no significant effect of lenti-ACE2 on BP of WKY rats was observed. Lenti-ACE2-treated SHR showed an 18% reduction in left ventricular wall thickness (1.52+0.04mm vs. 1.86 + 0.04mm in lenti-EGFP, p<0.01). In addition, there was a 12% increase in left ventricular end diastolic and 21% increase in end systolic diameters in lenti-ACE2 treated SHR. Finally, lenti-ACE2 treatment resulted in a significant attenuation of perivascular fibrosis in the SHR. In contrast, ACE2 gene transfer did not influence any of these parameters in WKY rats. These observations demonstrate that ACE2 over expression exerts protective effects on high BP and cardiac pathophysiology induced by hypertension in the SHR.
