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.