Association of hydrogen sulfide with alterations of monocyte chemokine receptors, CCR2 and CX3CR1 in patients with coronary artery disease.

Abstract

OBJECTIVES:

Recent data in human and mice suggest that monocyte chemokine receptors CX3CR1 and CCR2 are involved in the pathogenesis of atherosclerosis. Our previous study showed that hydrogen sulfide, a novel gaseous mediator hampered the progression of atherosclerosis in fat-fed apoE(-/-) mice with downregulating CX3CR1 and CX3CL1 expressions. However, there is a paucity of information regarding the clinical association between endogenous H2S metabolism and alterations of monocyte chemokine receptors in patients with cardiovascular disease. Therefore, in this study, we investigated circulating monocyte heterogeneity with differential expressions of CCR2 and CX3CR1 and its relevance to plasma H2S level in patients with coronary artery disease (CAD).

METHODS:

Sixty-three CAD patients with acute coronary syndrome (ACS, n = 46) or stable angina pectoris (SAP, n = 17) undergoing either percutaneous coronary intervention or coronary angiography and eleven non-CAD patients were enrolled in the study. Plasma levels of H2S as well as chemokines (CCL2 and CX3CL1) and expressions of CCR2 and CX3CR1 on peripheral monocytes were measured.

RESULTS:

It was found that plasma H2S level was significantly reduced, whereas plasma CCL2 and CX3CL1 levels were substantially elevated in patients with ACS, as compared with patients with SAP or non-CAD patients. Furthermore, patients with ACS had significantly higher proportion of CD14(+)CCR2(+)CX3CR1(+) and CD14(+)CCR2(-)CX3CR1(+) monocytes but lower percentage of CD14(+)CCR2(+)CX3CR1(-) monocytes than SAP or non-CAD patients did. Lastly, plasma H2S level showed a significantly negative correlation with the proportion of CD14(+)CCR2(+)CX3CR1(+) monocytes, but not other monocyte subsets.

CONCLUSIONS:

These data indicate that decreased endogenous H2S production may predispose stable CAD patients to rupture of vulnerable plaque and thus to ACS, probably in relation to circulating monocyte phenotypic transformation with differential expressions of CCR2 and CX3CR1.

• Authors: Lin Gao, Zuojun Xu, Zhaofang Yin, Kan Chen, Changqian Wang, Huili Zhang
• Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 64 Issue 8 Pg. 627-35 (Aug 2015) ISSN: 1420-908X [Electronic] Switzerland
• PMID: 26123579 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCR2 protein, human
• CX3C Chemokine Receptor 1
• CX3CR1 protein, human
• Receptors, CCR2
• Receptors, Chemokine
• Hydrogen Sulfide

Topics

• Aged
• Aged, 80 and over
• CX3C Chemokine Receptor 1
• Coronary Angiography
• Coronary Artery Disease (blood, metabolism)
• Female
• Humans
• Hydrogen Sulfide (blood)
• Male
• Middle Aged
• Monocytes (metabolism)
• Receptors, CCR2 (blood, metabolism)
• Receptors, Chemokine (blood, metabolism)