Myocardial infarction (MI) is the most common cause of heart failure. Within two weeks after MI, monocytes accumulate in the wounded muscular tissue of the heart (myocardium). Whether monocyte infiltration into the heart exacerbates MI or aids in its repair has perplexed scientists for quite some time. Early studies suggested that the infiltrating monocytes were both destructive and reparative, but scientists were unsure as to exactly how this was possible (Nahrendorf et al. 2010).
The answer was buried in the existence of monocyte subsets that respond to MI in a temporally biphasic manner (Gordon and Taylor 2005). Murine studies showed that on days 1-4 after MI, proinflammatory Ly-6Chigh monocytes dominate the myocardium and promote digestion of the wounded heart tissue and removal of necrotic debris (Phase 1). These monocytes subsequently abate, and between days 4 and 8, the reparative Ly-6Clow monocytes dominate and induce repair (Phase 2) (Nahrendorf et al. 2010).
This biphasic monocyte response is necessary for proper healing after MI. This has also been demonstrated in humans. A longitudinal study of 36 patients with acute MI showed that after two weeks, inflammatory CD16- monocytes initially expand, peaking on day 2.6. This was followed by the accumulation of reparative CD16+ monocytes, which peaked on day 4.8. (Tsujioka et al. 2009).
This paradigm shift in our understanding of monocytes in heart disease from a monophasic to a biphasic response certainly opens up exciting therapeutic opportunities for MI. Specifically, it could be beneficial to modulate the timing of monocyte recruitment to favor tissue repair. It would also be useful to target specific recruitment mechanisms to control the distinct monocyte phases.
So what do monocytes have to do with the heart? It turns out that in heart disease, specifically MI, their main role is to repair the heart.
To learn more about monocyte lineage, development and characterization of monocyte subtypes, check out our monocyte mini-review.
Also check out a wide range of antibodies for studying the role of monocytes in your specific experimental model.