Activation pattern of ACE2/Ang-(1-7) and ACE/Ang II pathway in course of heart failure assessed by multiparametric MRI in vivo in Tg{alpha}q*44 mice

Here we analyzed systemic (plasma) and local (heart/aorta) changes in ACE/ACE-2 balance in Tgαq*44 mice in course of heart failure (HF). Tgαq*44 mice with cardiomyocyte specific Gαq overexpression and late onset of HF were analyzed at different age for angiotensin pattern in plasma, heart and aorta using liquid chromatography/mass spectrometry, for progression of HF by in vivo magnetic resonance imaging under isoflurane anesthesia and for exercise capacity by voluntary wheel running. Six-month-old Tgαq*44 mice displayed decreased ventricle radial strains and impaired left atrial function. At 8-10-month Tgαq*44 mice showed impaired systolic performance, reduced voluntary wheel running, but exhibit preserved inotropic reserve. At 12 month Tgαq*44 mice demonstrated a severe impairment of basal cardiac performance and modestly compromised inotropic reserve with reduced voluntary wheel running. Angiotensin analysis in plasma revealed increase in concentration of angiotensin-(1-7) in 6-10-month-old Tgαq*44 mice. However, at 12-14-month-old Tgαq*44 mice, increase angiotensin-II was noted with a concomitant increase in Ang III, IV, angiotensin A and angiotensin-(1-10). The pattern of changes in the heart and in the aorta was also compatible with activation of ACE-2 followed by activation of ACE pathway. In conclusion, mice with cardiomyocyte Gαq protein overexpression develop HF that is associated with activation of the systemic and local ACE/Ang II pathway. However, it is counterbalanced by a prominent ACE2/Ang-(1-7) activation, possibly allowing to delay decompensation.

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