Sex Influence on Autophagy Markers and miRNAs in Basal and Angiotensin II-Treated Human Umbilical Vein Endothelial...

Cardiovascular diseases (CVD) display many sex and gender differences, and endothelial dysfunction, angiotensin II (Ang II), and autophagy represent key factors in the autophagic process Therefore, we studied whether Ang II modulates the mentioned processes in a sex-specific way in HUVECs obtained from healthy male and female newborns. In basal HUVECs, the Parkin gene and protein were higher in FHUVECs than in MHUVECs, while the Beclin-1 protein was more expressed in MHUVECs, and no other significant differences were detected. Ang II significantly increases LAMP-1 and p62 protein expression and decreases the expression of Parkin protein in comparison to basal in MHUVECs. In FHUVECs, Ang II significantly increases the expression of Beclin-1 gene and protein, and Parkin gene. The LC3 II/I ratio and LAMP-1 protein were significantly higher in MHUVECs than in FHUVECs, while Parkin protein was significantly more expressed in Ang II-treated FHUVECs than in male cells. Ang II affects the single miRNA levels: miR-126-3p and miR-133a-3p are downregulated and upregulated in MHUVECs and FHUVECs, respectively. MiR-223 is downregulated in MHUVEC and FHUVECs. Finally, miR-29b-3p and miR-133b are not affected by Ang II. Ang II effects and the relationship between miRNAs and organelles-specific autophagy is sex-dependent in HUVECs. This could lead to a better understanding of the mechanisms underlying sex differences in endothelial dysfunction, providing useful indications for innovative biomarkers and personalized therapeutic approaches.