The Transient Receptor Potential Vanilloid 2 Cation Channel is Abundant in Macrophages at the Peri-infarct Zone and May Be Involved in Necrotic Cardiomyocytes Phagocytosis 

Background: A new super-family of channels that may have a role in cardiac calcium homeostasis has recently been described. These are non-selective and non-voltage-gated transient receptor potential (TRP) channels; most of them are permeable for Ca²⁺ and gated by diverse stimuli. We have previously shown that the expression level of one of which, TRPV2, is exclusively upregulated in the heart 3-5 days post myocardial infarction. Further analysis, using IHC and flow cytometry techniques, has demonstrated that the invading monocytes maturing to active macrophages merely harbor the documented elevated expression of this channel.

Methods: Murine leukemia macrophage cell line, Raw 264.7, and rat alveolar macrophage cell line NR3838 were pre-treated with the semi-specific inhibitor ruthenium red or transiently transfected with a specific TRPV2 siRNA. The macrophages were then allowed to migrate towards hypoxic condition media of the murine cariomoyocyte cell line HL-1 or the rat cardiac myoblast line C9H2, respectively, using a transwell migration assay. Four hours later, the macrophage cells migrating to the bottom side of the inserts were fixed, stained and counted.

Results: Following inhibition of the TRPV2 channel, the number of migrating macrophages towards condition media of hypoxic cardiomyocytes was significantly reduced. The data suggest that TRPV2, which is highly abundant on the peri-infarct macrophages, may mediate their migration capacity towards necrotic cardiomyocytes in order to eliminate them by phagocytosis.

Conclusion: TRPV2 may play an important role in post MI phagocytosis processes. The data stand in line with recent publications suggesting that TRPV2 translocation from the intracellular compartments to the cell membrane may enhance the cytoskeletal organization necessary for phagocytic receptor clustering- the macrophage podosome;  which eventually enhances the migration capacity of the macrophages by regulating the increase in Ca²⁺ entry. The data may pave the way for identifying new targets and novel treatments for post MI patients.