Cha Ed, Hong Sung Ho, La Vy, Madabhushi Pranav, Teramoto Darren, Fung Cameron, Thankam Finosh G
Department of Translational Research, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA.
Department of Biology, University of California San Diego, San Diego, CA 92093, USA.
Biochem Cell Biol. 2025 Jan 1;103:1-15. doi: 10.1139/bcb-2024-0210. Epub 2024 Dec 17.
Epicardial adipose tissue (EAT) is a rich source of EAT-derived stromal cells (EATDS), which possess regenerative potential. CRSP2, HSP27, IL8, HSP90, and Cofilin 1 were detected in the secretome of left ventricular stromal cells under ischemia challenge. However, the association of these genes in the EAT and EATDS remain understudied. We aim to assess the status of cofilin 1, CRSP2, HSP27, IL8, and HSP90 in the EAT of myocardial infarction (MI) and coronary artery bypass graft (CABG) swine models and in vitro stimulated ischemic EATDS. Expression status of these proteins in EAT were assessed by immunostaining, and in EATDS using qRT-PCR, immunostaining, and Western blot. EATDS phenotyping was performed using sc-RNAseq analysis. Cofilin 1 was increased while the other four genes were decreased in the CABG. IL8 and HSP90 were increased, while CRSP2, HSP27, and cofilin 1 were decreased in the MI group. Similar trend was displayed in the expression of these genes in EATDS. Additionally, EATDS displayed versatile phenotypes at single cell resolution based on the differential expression of various gene signatures. The findings revealed novel insights into EAT/EATDS biology and further understanding regarding the EATDS sub-phenotypes would open novel avenues in translational cardiology.
心外膜脂肪组织（EAT）是心外膜脂肪组织来源的基质细胞（EATDS）的丰富来源，这些细胞具有再生潜力。在缺血挑战下，左心室基质细胞的分泌组中检测到CRSP2、HSP27、IL8、HSP90和丝切蛋白1。然而，这些基因在EAT和EATDS中的关联仍未得到充分研究。我们旨在评估丝切蛋白1、CRSP2、HSP27、IL8和HSP90在心肌梗死（MI）和冠状动脉搭桥术（CABG）猪模型的心外膜脂肪组织以及体外刺激的缺血性EATDS中的状态。通过免疫染色评估这些蛋白质在EAT中的表达状态，并使用qRT-PCR、免疫染色和蛋白质印迹法评估其在EATDS中的表达状态。使用单细胞RNA测序分析进行EATDS表型分析。在CABG中，丝切蛋白1增加，而其他四个基因减少。在MI组中，IL8和HSP90增加，而CRSP2、HSP27和丝切蛋白1减少。这些基因在EATDS中的表达也呈现出类似趋势。此外，基于各种基因特征的差异表达，EATDS在单细胞分辨率下表现出多种表型。这些发现揭示了关于EAT/EATDS生物学的新见解，对EATDS亚表型的进一步了解将为转化心脏病学开辟新途径。
