Key result
MAERL knockdown restores macrophage efferocytosis and curbs inflammation in atherosclerosis by targeting TGM2.
The MAERL/TGM2 pathway in macrophages is identified as a key regulatory mechanism in homocysteine-induced atherosclerosis, highlighting a potential therapeutic target.
Atherosclerotic cardio-cerebrovascular diseases remain the leading contributor to global disease burden and mortality. Impaired efferocytosis—the clearance of apoptotic cells by macrophages—is known to exacerbate inflammation and promote necrotic core formation within atherosclerotic plaques. Hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis development. However, the role of long non-coding RNAs (lncRNAs) induced by Hcy in this process remains largely unexplored. Here, we demonstrate that Hcy impairs macrophage efferocytosis and enhances inflammation in atherosclerosis, both in HMD-fed ApoE-/- mice and in RAW264.7 cells treated with Hcy. We further identify a markedly up-regulated lncRNA in Hcy-induced macrophages, termed macrophage efferocytosis-related lncRNA (MAERL). Knockdown of MAERL attenuated the impairment of efferocytosis and reduced inflammation. Mechanistically, MAERL interacts with and inhibits TGM2, thereby significantly suppressing macrophage efferocytosis and promoting inflammation. Collectively, these findings reveal a MAERL/TGM2 pathway in macrophages as a key regulatory mechanism in the development of atherosclerosis.
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Xiao et al. (2026) studied Atherosclerosis. MAERL knockdown vs. Control was evaluated on Macrophage efferocytosis and inflammation. Knockdown of the homocysteine-induced lncRNA MAERL attenuated the impairment of macrophage efferocytosis and reduced inflammation by interacting with and inhibiting TGM2 in atherosclerosis models.
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