Key result
Low sphingomyelin is linked to AF, while supplementation alleviates murine AF by suppressing Rap1.
Why the study?
Lipid metabolism abnormalities are frequently associated with cardiovascular diseases, but the regulatory roles of lipids in atrial fibrillation remain unclear.
Does sphingomyelin supplementation reduce AF susceptibility and atrial fibrosis in models of atrial fibrillation?
Case-Control (n=100)
Does sphingomyelin supplementation reduce AF susceptibility and atrial fibrosis in models of atrial fibrillation?
Sphingomyelin levels are markedly reduced in atrial fibrillation, and targeting sphingomyelin metabolism or the downstream Rap1 pathway represents a novel potential therapeutic strategy for mitigating AF.
Sphingomyelin supplementation may attenuate AF in mouse models; leaves open its therapeutic potential in human atrial fibrillation.
AIMS: Atrial fibrillation (AF) has emerged as one of the most prevalent cardiac arrhythmias globally, with its incidence continuously rising, thereby elevating it to a major public health concern. The heart is known for its high lipid content, and disorders or abnormalities in lipid metabolism are frequently associated with cardiovascular diseases. This study aimed to investigate the regulatory roles of lipids in AF. METHODS AND RESULTS: Using tree-based ensemble learning-assisted lipidomics, sphingomyelin was identified as a key differential metabolite and found to be significantly reduced in AF patients. Exogenous supplementation of sphingomyelin significantly attenuated acetylcholine-CaCl2-induced and angiotensin II-induced AF, fibrosis, and inflammation in mice. Furthermore, decreased sphingomyelin levels were attributed to increased activity of sphingomyelin phosphodiesterases (SMPDs) under AF conditions. Mechanistically, RNA-Seq analysis demonstrated that sphingomyelin inhibits AF-induced activation of the Rap1 signalling pathway, a finding corroborated by overexpression and knockdown of RAP1 in vivo. CONCLUSION: Together, these findings highlight the therapeutic potential of sphingomyelin and SMPD inhibitors in mitigating AF through inhibition of the Rap1 signalling pathway, thereby establishing the targeting of sphingomyelin metabolism as a viable and novel treatment strategy for AF.
No takes yet. Share an insight, caveat, or question.
Wang et al. (2026) conducted a case-control in Persistent Atrial Fibrillation (n=100). Sphingomyelin levels vs. Healthy controls was evaluated on Differential serum lipid profile (sphingomyelin reduction). Sphingomyelin levels were significantly reduced in the serum of patients with atrial fibrillation, and exogenous supplementation in mice alleviated AF, fibrosis, and inflammation by suppressing the Rap1 signaling pathway.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: