TRPV2 Knockout Mice Demonstrate Better Cardiac Performance Following Myocardial Infarction Relative to Their Wild-type Counterparts Potentially due to Attenuated Macrophage-Dependent Phagocytosis

Background: We have recently shown that the expression of the transient receptor potential vanilloid 2 channel, TRPV2, is upregulated in the peri-infarct zone 3-5 days following an acute myocardial infarction (AMI). Further analysis has demonstrated that invading monocytes maturing to macrophages merely harbor the documented elevated expression of this channel (Entin-Meer, PLoS ONE, 2014).

Purpose: Analyze the potential involvement of TRPV2-expressing macrophages in the recovery from AMI.

Methods: 1. Macrophages derived from wild-type (WT) or TRPV2- knockout (KO) mice were isolated and their migration capacity towards conditioned media (CM) of HL-1 cardiomyocytes was tested.
2. TRPV2-KO or WT mice were induced with AMI by ligation of the left anterior descending artery (LAD). Cardiac parameters were obtained by echocardiography 1 day and 30 days post infarction. The relative change in the ejection fraction (EF) and in the endocardial fractional area change (FAC) between baseline (day 1) and day 30 were calculated and statistical significance was determined (SPSS).

Results: WT macrophages, but not KO macrophages, migrated towards HL-1 CM in the in vitro analysis. Interestingly, the in vivo study showed that while EF was significantly decreased in the WT animals from 44.1 ± 2.3 on day 1 to 32.4 ± 1.8 on day 30 (n=9, p<0.001), EF was only slightly and insignificantly reduced in the KO animals (40.9± 3.2 and 37.5± 3.7 on day 1 versus day 30, respectively; n=14, p=0.08). Likewise, endocardial FAC was reduced from 40.0±1.7 on day 1 to 28.6± 1.9 on day 30 in the WT mice (p<0.001). In the KO animals, FAC was only moderately reduced (38.8± 2.3 versus 35.1± 3.7 on day 1 versus day 30, respectively; p=0.05).

Conclusion: Our data suggest that TRPV2-expressing macrophages enhance phagocytosis processes following AMI. Knockout of the TRPV2 channel may attenuate macrophage-dependent pro-inflammatory processes and result in better cardiac recovery.