Long Noncoding RNA H19 Regulates the Foam Cell Formation of Vascular Smooth Muscle Cells by Inhibiting microRNA-107 to Activate the CD40/CD40L Pathway.

Objective: Atherosclerosis (AS) represents a life-threatening condition involving vascular inflammation and posing a high risk of death, yet effective therapeutic strategies remain limited. This research focused on elucidating the regulatory function of the long noncoding RNA H19 (lncRNA H19) in AS and its underlying molecular mechanisms.

Methods: To conduct the research, an AS mouse model induced by a high-fat diet and a vascular smooth muscle cell (VSMC) model exposed to oxidized low-density lipoprotein (ox-LDL) treatment were respectively constructed.

Results: There were significant aortic pathological changes and increased foam cell formation in the AS group versus the Control group. ox-LDL treatment effectively enhanced VSMC proliferation, VSMC migration, foam cell formation, and inflammatory cytokine secretion (TNF-α and IL-6), along with decreased microRNA-107 (miR-107) expression, while simultaneously increasing CD40 expression in VSMCs, all of which were reversed by knockdown of H19. Additionally, inhibition of miR-107 increased the migration and proliferation, inflammatory cytokine secretion, as well as foam cell formation in ox-LDL-treated VSMCs subjected to H19 knockdown. Moreover, miR-107 was confirmed to directly target CD40, and CD40 overexpression mitigated H19 knockdown-induced effects on ox-LDL-treated VSMCs.

Conclusion: H19 regulates the progression of AS by modulating the CD40/CD40L axis through regulation of miR-107. Targeting H19/miR-107 and CD40/CD40L may serve as a potential treatment strategy for AS.