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ACE2 gene transfer attenuates hypertension-linked pathophysiological changes in the SHR
Carlos Díez-Freire1, Jorge Vázquez, María F Correa de Adjounian
1Department of Physiology and Functional Genomics, College of Medicine, and Advanced Magnetic Resonance Imaging and Spectroscopy Facility at the McKnight Brain Institute, University of Florida, Gainesville, Florida 32610, USA.
Physiological Genomics
|June 22, 2006
Summary
Gene transfer of angiotensin-converting enzyme-2 (ACE2) effectively lowered high blood pressure and improved cardiac dysfunction in hypertensive rats. This study highlights ACE2
Area of Science:
- Cardiovascular Research
- Gene Therapy
- Hypertension Studies
Background:
- Angiotensin-converting enzyme-2 (ACE2) plays a key role in regulating angiotensin peptides.
- ACE2 is a potential therapeutic target for cardiovascular diseases.
Purpose of the Study:
- To investigate the effects of ACE2 gene transfer on high blood pressure (BP) and cardiac dysfunction in spontaneously hypertensive rats (SHR).
Main Methods:
- Intracardiac injection of lentiviral vectors carrying murine ACE2 or enhanced green fluorescent protein (EGFP) in young SHR and WKY rats.
- Evaluation of systolic BP, cardiac function, and perivascular fibrosis 4 months post-transduction.
Main Results:
- ACE2 gene transfer significantly reduced systolic BP in SHR compared to controls.
- ACE2 treatment led to reduced left ventricular wall thickness and attenuated perivascular fibrosis in SHR.
- No significant effects on BP or cardiac parameters were observed in normotensive WKY rats.
Conclusions:
- Overexpression of ACE2 via gene transfer demonstrates protective effects against hypertension-induced cardiac pathophysiology in SHR.
- ACE2 gene therapy offers a promising approach for managing hypertension and associated cardiac complications.