Hydrogen sulfide, as a novel gaseous mediator, has been suggested to play a key role in atherogenesis. However, the precise mechanisms by which H2S affects atherosclerosis remain unclear. Therefore, the present study aimed to investigate the potential role of H2S in atherosclerosis and the underlying mechanism with respect to chemokines (CCL2, CCL5 and CX3CL1) and chemokine receptors (CCR2, CCR5, and CX3CR1) in macrophages. Mouse macrophage cell line RAW 264.7 or mouse peritoneal macrophages were pre-incubated with saline or NaHS (50 µM, 100 µM, 200 µM), an H2S donor, and then stimulated with interferon-γ (IFN-γ) or lipopolysaccharide (LPS). It was found that NaHS dose-dependently inhibited IFN-γ or LPS-induced CX3CR1 and CX3CL1 expression, as well as CX3CR1-mediated chemotaxis in macrophages. Overexpression of cystathionine γ-lyase (CSE), an enzyme that catalyzes H2S biosynthesis resulted in a significant reduction in CX3CR1 and CX3CL1 expression as well as CX3CR1-mediated chemotaxis in stimulated macrophages. The inhibitory effect of H2S on CX3CR1 and CX3CL1 expression was mediated by modulation of proliferators-activated receptor-γ (PPAR-γ) and NF-κB pathway. Furthermore, male apoE−/− mice were fed a high-fat diet and then randomly given NaHS (1 mg/kg, i.p., daily) or DL-propargylglycine (PAG, 10 mg/kg, i.p., daily). NaHS significantly inhibited aortic CX3CR1 and CX3CL1 expression and impeded aortic plaque development. NaHS had a better anti-atherogenic benefit when it was applied at the early stage of atherosclerosis. However, inhibition of H2S formation by PAG increased aortic CX3CR1 and CX3CL1 expression and exacerbated the extent of atherosclerosis. In addition, H2S had minimal effect on the expression of CCL2, CCL5, CCR2 and CCR5 in vitro and in vivo. In conclusion, these data indicate that H2S hampers the progression of atherosclerosis in fat-fed apoE−/− mice and downregulates CX3CR1 and CX3CL1 expression on macrophages and in lesion plaques.

This study provides evidence that preoperative serum levels of haptoglobin could serve as an independent prognostic factor in patients presenting with epithelial ovarian cancer.

Hydrogen sulfide (H2S) has been recognized as an important gasotransmitter exerting various physiological effects, especially in the cardiovascular system. Herein we investigated the cardioprotective effects of a novel long-term and slow-releasing H2S donor, DATS-MSN, using in vivo myocardial ischemia/reperfusion (I/R) models and in vitro hypoxia/reoxygenation cardiomyocyte models. Unlike the instant-releasing pattern of sodium hydrosulphide (NaHS), the release of H2S from DATS-MSN was quite slow and continuous both in the cell culture medium and in rat plasma (elevated H2S concentrations during 24 h and 72 h reperfusion). Correspondingly, DATS-MSN demonstrated superior cardioprotective effects over NaHS in I/R models, which were associated with greater survival rates, reduced CK-MB and troponin I levels, decreased cardiomyocyte apoptosis index, increased antioxidant enzyme activities, inhibited myocardial inflammation, greater reduction in the infarct area and preserved cardiac ejection fraction. Some of these effects of DATS-MSN were also found to be superior to classic slow-releasing H2S donor, GYY4137. In in vitro experiments, cardiomyocytes injury was also found to be relived with the use of DATS-MSN compared to NaHS after the hypoxia/reoxygenation processes. The present work provides a novel long-term and slow-releasing H2S donor and an insight into how the release patterns of H2S donors affect its physiological functionality.