Cardiac Exosomes in Ischemic Heart Disease—A Narrative Review

Figure 1. Schematic overview of remote ischemic preconditioning (RIPC) stimulating exosome production resulting in myocardial protection. (A) Repeated cycles of ischemia reperfusion induced by blood pressure cuff inflation at the arm. (B) RIPC induces shear stress in the vasculature. (C) The shear stress stimulates the humoral system to release cardioprotective factors into the blood. (D) Cardioprotective factors are carried by the blood. (E) Cardioprotective factors reach the myocardium and activate cardioprotective signaling pathways that lead to reduced tissue damage and improved function.

Figure 2. Simplified overview of major protective signaling pathways involved in RIPC, the reperfusion injury salvage (RISK) pathway, and the survivor activating factor enhancement (SAFE) pathway. Abbreviations: G protein-coupled receptors (GPCRs); MEK1/2, also known as mitogen-activated protein kinase 1/2; Erk1/2, extracellular-regulated kinases 1/2; PI3K, phosphatidylinositol-4, 5-bisphosphate3-kinase; Bcl-2-associated death promoter (BAD); Bcl-2-associated X protein (BAX); glycogen synthase kinase-3ß (GSK3ß); mitochondrial permeability transition pore (mPTP). Akt, also known as protein kinase B; nitric oxide synthase 3/endothelial nitric oxide synthase (NOS3/eNOS) and nitric oxide (NO); Janus kinase (JAK), protein kinase G (PKG); protein kinase C (PKC), mechanistic target of rapamycin (mTOR); sodium hydrogen exchanger (NHE); signal transducer and activator of transcription 3, STAT-3. P indicates phosphorylation. Red lines indicate inhibition.

Figure 3. Overview of the cardioprotective proteins found in exosomes secreted from different cells of the myocardium.

Figure 4. Cardioprotective factors associated with the diagnosis and prognosis of heart failure and acute myocardial infarction. miRs in the blue box are associated with multiple pathologies; miRs in the yellow box and proteins in the green box are associated with a single pathology.