Neu therapy for delaying post-ischaemic heart failure development: Angiotensin II receptor 2 agonist Vasoconstriction-Inhibiting Factor (VIF)  improves post-ischaemic left ventricular function in mice

Lei Hua (Aachen)1, K. Quach (Aachen)1, J. Jankowski (Aachen)1, A. Baleanu-Curaj (Aachen)1

1Uniklinik RWTH Aachen Institut für Molekulare Herz-Kreislaufforschung (IMCAR) Aachen, Deutschland



The renin-angiotensin-aldosterone system is essential in blood pressure regulation not only in preventing cardiovascular disease progression or cardiovascular acute events, but also in the drug therapy following an acute myocardial infarction (MI) to avoid excessive left ventricular (LV) remodelling and development of heart failure.

A recently identified peptide named VIF (Vasoconstriction-Inhibiting Factor) which has the capacity to diminish the vasoconstrictive effect of Ang-II by targeting the AT2-R was isolated from adrenal glands and was identified in higher concentrations in patients with heart failure. Based on its vasoregulatory effect, we hypothesized that VIF might be elevated in patients suffering from heart failure as a counterregulatory effect and might have additional protective effects in the healing process of MI. Therefore, clinical application of VIF might be extended to the multiple and high-risk patients aiming at a benefit for the in-clinic treatment of MI in order to sustain a better function of the left ventricle and delay the heart failure development.


Eight weeks old wild type mice subjected to open-chest permanent left anterior descending coronary artery ligature were treated with VIF via osmotic pump starting with the day of the MI onset for 2 weeks. Blood pressure and left ventricular ejection fraction (LV-EF) were measured at 28 days (28 d) post-MI in both VIF-treated and control untreated group, as well in mice treated with ß-blocker. Additionally, serial sections of paraffin embedded hearts explanted at different time points post-MI were performed for measuring the infarction size as well as the invasion sequence of inflammatory cells in the infarcted area.


VIF reduced the mortality post-MI (35% deaths post-MI) and had an additive effect to ß-blocker therapy (20% deaths post-MI) when compared to control untreated group (45% deaths post-MI). VIF treatment reduced the blood pressure level post-MI in both VIF-treated and ß-blocker-co-treated groups, in contrast with the VIF-untreated group (p=0.002). The LV-ejection fraction (EF) was significantly improved in VIF-treated (p=0,002) and ß-blocker co-treated mice (p=0.01). Additionally, VIF treatment induced a significant decrease in the infarction size from 50.5% of the left ventricle volume in the untreated group to 26.3% in the VIF-treated group (p=0,047) by improving the cardiomyocytes survival in the border zone (p=0,010). Furthermore, an increased level of M2 macrophages  recruitment at 4 and 7d post-MI was measured in VIF-treated group in comparison with the untreated group. Additionally, VIF modulated myofibroblasts accumulation in the scar tissue and led to a morphologically different scar formation as seen in two-photon laser microscopy.


VIF treatment has a positive influence on the healing process after MI by protecting the cardiomyocytes towards ischemia and sustaining the infiltration of reparatory monocytes, modulating myofibroblasts infiltration, and in this way allowing a smaller scar size formation leading to a preserved LV-EF. Moreover, VIF treatment can be combined with one of the pillars of the heart failure medication, namely the ß-blocker therapy, showing a positive additive effect to the ß-blocker therapy. Therefore, VIF might represent a candidate for treating the ischaemic induced heart failure.

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