Hydrogen sulfide inhibits early development of atherosclerosis by modulating macrophage uptake of oxidized lipoproteins

Abstract

Atherosclerosis, a major cause of cardiovascular diseases, is characterized by the accumulation of oxidized lipoproteins (ox-LDL) within arterial walls, leading to inflammation and plaque formation. Hydrogen sulfide (H2S) has demonstrated anti-inflammatory and vascular protective properties, but its role in modulating macrophage endocytosis of ox-LDL and its impact on early atherosclerosis development remains unclear. Macrophage cultures were utilized for ox-LDL uptake experiments. Macrophages were pretreated with NaHS (50 μmol/L) or propargylglycine (PPG, 3 mmol/L) for one hour, followed by incubation with DiI-ox-LDL (10 μg/mL) for an additional two hours. DiI-ox-LDL uptake was visualized using live cell imaging. The expression of scavenger receptors CD36 and SR-A was assessed through immunofluorescent staining and Western blot analysis. To determine the intracellular signal transduction pathways involved, macrophages were pretreated with NF-κB pathway blocker PDTC or MAPK inhibitor PD98059 before the addition of NaHS. NaHS significantly inhibited ox-LDL uptake by macrophages, while PPG treatment markedly increased this process. Immunocytochemistry and Western blot analysis revealed that the expressions of CD36 and SR-A were induced by ox-LDL but inhibited by NaHS in a concentration- and time-dependent manner. Furthermore, H2S down-regulated ox-LDL receptors CD36 and SR-A through the NF-κB signal pathway. H2S inhibits early atherosclerosis development by modulating macrophage uptake of ox-LDL through the down-regulation of CD36 and SR-A receptors via the NF-κB signaling pathway. These findings provide new evidence for the role of H2S in atherosclerosis and its potential therapeutic value.