Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, Box 596, Uppsala, S-751 24, Sweden.
Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, S-182 88, Sweden.
BMC Genomics. 2024 Oct 7;25(1):938. doi: 10.1186/s12864-024-10851-9.
Epicardial adipose tissue (EAT) surrounds the heart and is hypothesised to play a role in the development of heart failure (HF). In this study, we first investigated the differences in gene expression between epicardial adipose tissue (EAT) and subcutaneous adipose tissue (SAT) in patients undergoing elective coronary artery bypass graft (CABG) surgery (n = 21; 95% male). Secondly, we examined the association between EAT and SAT in patients at risk for HF stage A (n = 12) and in pre-HF patients, who show signs but not symptoms of HF, stage B (n = 9).
The study confirmed a distinct separation between EAT and SAT. In EAT 17 clusters of genes were present, of which several novel gene modules are associated with characteristics of HF. Notably, seven gene modules showed significant correlation to measures of HF, such as end diastolic left ventricular posterior wall thickness, e', deceleration time and BMI. One module was particularly distinct in EAT when compared to SAT, featuring key genes such as FLT4, SEMA3A, and PTX3, which are implicated in angiogenesis, inflammation regulation, and tissue repair, suggesting a unique role in EAT linked to left ventricular dysfunction. Genetic expression was compared in EAT across all pre-HF and normal phenotypes, revealing small genetic changes in the form of 18 differentially expressed genes in ACC/AHA Stage A vs. Stage B.
The roles of subcutaneous and epicardial fat are clearly different. We highlight the gene expression difference in search of potential modifiers of HF progress. The true implications of our findings should be corroborated in other studies since HF ACC/AHA stage B patients are common and carry a considerable risk for progression to symptomatic HF.
心外膜脂肪组织(EAT)环绕心脏,据推测在心衰(HF)的发展中发挥作用。在这项研究中,我们首先研究了接受择期冠状动脉旁路移植术(CABG)的患者(n=21;95%为男性)心外膜脂肪组织(EAT)和皮下脂肪组织(SAT)之间基因表达的差异。其次,我们检查了 HF A 期(n=12)和 Pre-HF 期(n=9)高危患者的 EAT 和 SAT 之间的相关性,Pre-HF 期患者出现 HF 但无症状,处于 B 期。
该研究证实了 EAT 和 SAT 之间的明显分离。EAT 中有 17 个基因簇,其中几个新的基因模块与 HF 的特征有关。值得注意的是,有七个基因模块与 HF 的测量值有显著相关性,如舒张末期左心室后壁厚度、e'、减速时间和 BMI。与 SAT 相比,EAT 中有一个模块特别明显,其特征基因包括 FLT4、SEMA3A 和 PTX3,它们参与血管生成、炎症调节和组织修复,提示 EAT 在左心室功能障碍方面具有独特的作用。对所有 Pre-HF 和正常表型的 EAT 进行基因表达比较,发现 ACC/AHA 阶段 A 与阶段 B 相比有 18 个差异表达基因的微小遗传变化。
皮下和心外膜脂肪的作用显然不同。我们强调基因表达的差异,寻找 HF 进展的潜在修饰因子。我们的发现的真正意义应该在其他研究中得到证实,因为 HF ACC/AHA 阶段 B 患者很常见,并且有进展为有症状 HF 的相当大的风险。