BackgroundFibro-fatty replacement of the myocardium plays a key role in the pathogenesis of arrhythmogenic cardiomyopathy (ACM) and may be associated with progressive heart failure (HF). We aimed to investigate the characteristic of the fibro-fatty tissues of ACM patients and the plasma chemokines levels according to HF burden.MethodsThe expression level of markers for brown, beige, and white fat of fibro-fatty tissues was determined using a quantitative real-time polymerase chain reaction. Lipidomics analysis of fibro-fatty tissues (n = 10 for normal control [NC]; n = 24 for ACM patients) was conducted using LC-MS. Single-cell RNA sequencing (n = 2 for NC; n = 6 for ACM patients) was used to compare the immune environment in the myocardium. Immunostaining and enzyme-linked immunosorbent assay were used to examine the expression of CCL3 in the myocardium and plasma samples, respectively.ResultsThe expression level of beige (TBX1 and TMEM26) and brown (TNFRSF9) fat markers were higher in the fibro-fatty tissues of ACM patients compared to NC. The fibro-fatty tissues revealed a significant increased level of saturated triglycerides (TGs) in ACM patients compared with NC. Single-cell RNA sequencing revealed the obvious accumulation of proinflammatory macrophages and a high expression level of proinflammatory markers in the myocardium of ACM patients compared to NC. The expression of CCL3 in the fibro-fatty tissues was positively correlated with HF progression in patients with ACM. Plasma CCL3 levels were significantly higher in patients with ACM compared to healthy volunteer. A total of 102 patients with ACM have been followed for a median of 7.8 years, indicating that plasma CCL3 levels could successfully predict the incidence of HF and heart transplantation (HTx)/death in patients with ACM (hazard ratio = 3.122 [95% confidence interval, 1.556-6.264]). The ROC curve analysis revealed the AUC value reached 0.814 for HF and 0.756 for HTx/death.ConclusionsThe increased level of saturated TGs and CCL3 in the fibro-fatty tissues might promote HF progression in ACM patients. Plasma CCL3 levels are useful for predicting HF-related adverse events in patients with ACM, but requiring further validation in larger and independent cohorts.
[1]Chinese Acad Med Sci & Peking Union Med Coll, Cardiomyopathy Res Grp, State Key Lab Cardiovasc Dis, Fuwai Hosp,Natl Ctr Cardiovasc Dis, 167A Beilishi Rd, Beijing 100037, Peoples R China.
[2]Chinese Acad Med Sci & Peking Union Med Coll, Fuwai Hosp, Beijing Key Lab Preclin Res & Evaluat Cardiovasc I, Natl Ctr Cardiovasc Dis,Anim Expt Ctr, Beijing 100037, Peoples R China.
[3]Chinese Acad Med Sci & Peking Union Med Coll, Fuwai Hosp, Natl Ctr Cardiovasc Dis, Dept Cardiac Surg, Beijing 100037, Peoples R China.
[4]Capital Med Univ, Beijing Shijitan Hosp, Galactophore Ctr, Galactophore Dept, Beijing, Peoples R China.
[5]Anzhen Hosp, Dept Cardiol, Beijing, Peoples R China.
[6]Univ Zurich, Ctr Mol Cardiol, Wagistr 12, CH-8952 Zurich, Switzerland.
[7]Chinese Acad Med Sci & Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Cardiol, State Key Lab Complex Severe & Rare Dis, Beijing, Peoples R China.
[8]Peking Union Med Coll & Chinese Acad Med Sci, Fuwai Hosp, Natl Ctr Cardiovasc Dis, Natl Clin Res Ctr Cardiovasc Dis, Beijing, Peoples R China.
[9]Kunming Med Univ, Fuwai Yunnan Hosp, Chinese Acad Med Sci, Dept Cardiac Surg,Affiliated Cardiovasc Hosp, Kunming, Peoples R China.
[10]Chinese Acad Med Sci, Shenzhen Key Lab Cardiovasc Dis, Fuwai Hosp, Shenzhen 518057, Peoples R China.
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