A lipid-busting lipoxygenase (LOX) enzyme triggers cardiac failure by luring troublemaking macrophages into the heart, according to Kayama et al. on page 1565.
Heart failure commonly follows heart attack, chronically high blood pressure, and heart disease. And macrophage build-up appears to accompany those conditions as they worsen. Here, Kayama and colleagues find that the enzyme 12/15-LOX is dramatically upregulated in the failing hearts of rodents, where it stimulates a macrophage attractant.
Mice whose hearts expressed excess 12/15-LOX accumulated macrophages and developed problematic pumping and cardiac fibrosis that eventually led to heart failure. Increased LOX activity boosted levels of the macrophage attractant MCP-1, and blocking MCP-1 signals reduced macrophage accumulation and restored normal heart function. The connection between the LOX and MCP-1 could also account for the enzyme's role in other heart disorders such as atherosclerosis.
LOX induces MCP-1 by metabolizing arachidonic acid into byproducts such as 12-HETE. This process occurred in cardiomyocytes, but the metabolite appears to trigger MCP-1 production by other heart cells. Fibroblasts and endothelial cells—but not cardiomyocytes—produced MCP-1 when treated with 12-HETE in vitro.
High cardiac pressure may call LOX into action suggest the authors, as inducing aortic constriction in another mouse model caused LOX activity and 12/15-HETE levels to increase.