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This article focuses on screening the major secreted proteins by the ischemia-challenged cardiac stromal fibroblasts (CF), the assessment of their expression status and functional role in the post-ischemic left ventricle (LV) and in the ischemia-challenged CF culture and to phenotype CF at single cell resolution based on the positivity of the identified mediators. The expression level of CRSP2, HSP27, IL-8, Cofilin-1, and HSP90 in the LV tissues following coronary artery bypass graft (CABG) and myocardial infarction (MI) and CF cells followed the screening profile derived from the MS/MS findings. The histology data unveiled ECM disorganization, inflammation and fibrosis reflecting the ischemic pathology. CRSP2, HSP27, and HSP90 were significantly upregulated in the LV-CABG tissues with a concomitant reduction ion LV-MI whereas Cofilin-1, IL8, Nrf2, and Troponin I were downregulated in LV-CABG and increased in LV-MI. Similar trends were exhibited by ischemic CF. Single cell transcriptomics revealed multiple sub-phenotypes of CF based on their respective upregulation of CRSP2, HSP27, IL-8, Cofilin-1, HSP90, Troponin I and Nrf2 unveiling pathological and pro-healing phenotypes. Further investigations regarding the underlying signaling mechanisms and validation of sub-populations would offer novel translational avenues for the management of cardiac diseases., (© 2024. The Author(s).)

Background: Despite the recent advancements in the cardiac regenerative technologies, the lack of an ideal translationally relevant experimental model simulating the clinical setting of acute myocardial infarction (MI) hurdles the success of cardiac regenerative strategies., Methods: We developed a modified minimally invasive acute MI model in Yucatan miniswine by catheter-driven controlled occlusion of LCX branches for regenerative cardiology. Using a balloon catheter in three pigs, the angiography guided occlusion of LCX for 10-15 minutes resulted in MI induction which was confirmed by the pathological ECG changes compared to the baseline control., Results: Ejection fraction was considerably decreased post-procedure compared to the baseline. Importantly, the highly sensitive MI biomarker Troponin I was significantly increased in post-MI and follow-up groups along with LDH and CCK than the baseline control. The postmortem infarct zone tissue displayed the classical features of MI including ECM disorganization, hypertrophy, inflammation, and angiogenesis confirming the MI at the tissue level., Conclusions: The present model possesses the advantage of minimal mortality, simulating the pathological features of clinical MI and the suitability for injectable regenerative therapies suggesting the translational significance in regenerative cardiology., Competing Interests: Conflict of Interest Statement The authors have read the journal’s authorship agreement and policy on disclosure of potential conflicts of interest. The authors declare no conflict of interest. No writing assistance was utilized in the production of this manuscript.

The global incidence of coronary artery diseases (CADs), especially myocardial infarction (MI), has drastically increased in recent years. Even though the conventional therapies have improved the outcomes, the post-MI complications and the increased rate of recurrence among the survivors are still alarming. Molecular events associated with the pathogenesis and the adaptive responses of the surviving myocardium are largely unknown. Focus on exosome-mediated signaling for cell-cell/matrix communications at the infarct zone reflects an emerging opportunity in cardiac regeneration. Also, cardiac tissue engineering provides promising insights for the next generation of therapeutic approaches in the management of CADs. In this article, we critically reviewed the current understanding on the biology of cardiac exosomes, therapeutic potential of exosomes, and recent developments in cardiac tissue engineering and discussed novel translational approaches based on tissue engineering and exosomes for cardiac regeneration and CADs.