Epithalon

Although the clinical application of cell-free tissue-engineered vascular grafts (TEVGs) has been proposed, vascular tissue regeneration mechanisms have not been fully clarified. Here, we report that monocyte subpopulations reconstruct vascular-like tissues through integrin signaling. An Arg-Glu-Asp-Val peptide-modified acellular long-bypass graft was used as the TEVG, and tissue regeneration in the graft was evaluated using a cardiopulmonary pump system and porcine transplantation model. In 1 day, the luminal surface of the graft was covered with cells that expressed CD163, CD14, and CD16, which represented the monocyte subpopulation, and they exhibited proliferative and migratory abilities. RNA sequencing showed that captured cells had an immune-related phenotype similar to that of monocytes and strongly expressed cell adhesion-related genes. In vitro angiogenesis assay showed that tube formation of the captured cells occurred via integrin signal activation. After medium- and long-term graft transplantation, the captured cells infiltrated the tunica media layer and constructed vascular with a CD31/CD105-positive layer and an αSMA-positive structure after 3 months. This finding, including multiple early-time observations provides clear evidence that blood-circulating monocytes are directly involved in vascular remodeling.

Acute exposure of isolated ventricular cardiomyocytes to non-opiate analogue of leu-enkephalin (NALE peptide: Phe-D-Ala-Gly-Phe-Leu-Arg) in a concentration of 100 μg/liter and 6-h incubation in NALE solution did not significantly change ATP-dependent K⁺ current, L-type Ca²⁺ current, p53 protein expression, and number of nucleoli in the cardiomyocyte nuclei. Incubation of cardiomyocytes with NALE (100 μg/liter) in combination with NOP receptor blocker J-113397 (1 mg/liter) was followed by an increase in Ca²⁺ L-type current and the number of p53⁺ cells. The exposure of cardiomyocytes to NALE in a concentration 1000 μg/liter induced similar changes in the studied parameters (increase in Ca²⁺ L-type current and number of p53⁺ cardiomyocytes); an increase in the mean number of nucleoli was also observed. Our findings suggest that NALE peptide has direct effect on cardiomyocytes and NOP receptors are involved in this effect.