Hamid Lotfimehr
, Narges Mardi, Reza Rahbarghazi
* , Mohammad Nori, Shahram Rabbani
Abstract
Introduction Blood re-establishment into ischemic myocardium can salvage cardiomyocytes from pathologic cardiac remodeling. Extracellular vesicles (EVs), especially exosomes (Exos), have been used as suitable nanocarriers for the delivery of cytokines to different tissues. Here, the therapeutic properties of YKL-40-loaded amniotic fluid Exos (YKL-40@AFExos) were assessed in infarcted rats. Methods Human AFExos were loaded with exogenous YKL-40 via sonication, and YKL-40@AFExos were injected directly into the border zone of ischemic myocardium in rats. After two weeks, rats were euthanized, and the angiogenesis properties and fibrotic changes were studied using histological examination and western blotting. Results Data indicated loading efficiency of YKL-40 onto AFExos was in the range of 55.5 ± 1.5%. Masson’s trichrome staining revealed the reduction of collagen fibers in rats that received YKL-40@AFExos compared to MI and YKL-40 groups (p<0.05). These features coincided with the reduction of recruited immune cells and an increase in viable cardiomyocytes. IHC staining confirmed the significant increase of alpha-smooth muscle actin (α-SMA) and von Willebrand factor (vWF) vessels in YKL-40@AFExos, AFExos, and YKL-40 groups compared to the MI rats (p<0.05). Administration of YKL-40@AFExos in MI rats significantly reduced apoptosis (Bax↓) and autophagic response (LC3-II/I ratio↓) (p<0.05). The injection of YKL-40 alone can promote angiogenesis via the local increase in VEGFR-1, but not VEGFR-2 and VEGFR. These values did not reach significant levels in YKL-40@AFExos and AFExos groups. Conclusion Transplantation of YKL-40@AFExos in infarcted rats led to regeneration of ischemic myocardium via enhancing angiogenesis and reduction of fibrotic changes, rather than YKL-40 peptide alone.