Introduction:

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). The vasoregulatory effects of the angiotensin peptides are mediated by the angiotensin II (Ang-II) type 1 receptor (AT1-R), with vasoconstrictive effects, and Ang-II type 2 receptor (AT2-R) and Mas receptor, with vasodilatative effects.

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. Based on its vasoregulatory effect, we hypothesized that VIF 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.

Method:

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.

Results:

VIF treatment preserved the blood pressure in both VIF-treated and ß-blocker-treated groups, in contrast with the VIF-untreated group which developed significant high blood pressure upon MI-induction (p=0.002). The LV-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 infarcted area (p=0,010) as evaluated with TUNEL-analysis of 1d post-MI histological slides. Furthermore, an increased level of reparatory monocyte recruitment at 4 and 7d post-MI was measured in VIF-treated group in comparison with the untreated group.

Conclusions:

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 and in this way allowing a smaller scar size formation leading to a preserved LV-EF.