Association of plasma macrophage colony-stimulating factor with cardiovascular morbidity and all-cause mortality in chronic hemodialysis patients

Abstract

Background Cardiovascular disease (CVD) events are the main cause of death in long-term hemodialysis (HD) patients. Macrophage colony- stimulating factor (M-CSF) is actively involved in the formation of atherosclerosis and causes plaque instability, thrombosis and the development of acute coronary syndromes. However, little information is available on the role of M-CSF in HD patients. We aimed to investigate the association between plasma M-CSF levels and CVD events as well as all-cause mortality in patients undergoing long-term HD. Methods Fifty two HD patients and 8 healthy controls were recruited in this study. HD patients were followed up from September 2014 to May 2017. The primary end point was CVD event, the secondary outcome was death from any cause. Patients were divided into two groups with low and high M-CSF levels based on the optimal cut-off value determined by the ROC curve. Cox regression analyses were used to assess the predictive value of plasma M-CSF for CVD events and all-cause mortality in HD patients. We tested the levels of plasma M-CSF and other inflammatory cytokines in surviving HD patients using ELISA or CBA kit. Results The average plasma level of M-CSF in 52 patients was approximately twice that of healthy controls (992.4 vs. 427.2 pg/mL; p < 0.05). During 32 months of follow-up, 26 patients (50.0%) had at least one CVD event and 8 patients (15.4%) died. The mean plasma M-CSF concentration increased in survivors after follow-up compared to that detected at baseline (1277.8 ± 693.3 vs. 997.2 ± 417.4 pg/mL; p < 0.05). Multivariate Cox regression analysis showed that plasma M-CSF is an independent risk factor for CVD events in HD patients ( p < 0.05). In the Cox regression model after adjusting for gender and age, high M-CSF levels were related to an increased risk of all-cause death ( p < 0.05). We also found that M-CSF levels were positively correlated with IL-6 and IL-18 levels (both p < 0.05), which are the major pathogentic cytokines that contribute to HD-related CVD events. Conclusion M-CSF is a prognostic factor for CVD events and all-cause mortality in HD patients.

The Role of Macrophage Dynamics in Atherosclerosis Analyzed Using a Petri Net-Based Model

“…The model suggests that inhibiting M-CSF significantly affects the formation of atherosclerotic plaques by altering macrophage behavior and inflammatory responses, while disturbances in cholesterol homeostasis continue to lead to lipid accumulation. This is supported by research indicating M-CSF's pivotal role in macrophage activation, foam cell creation, and chronic inflammation, which are essential for plaque development and instability [44,46,49]. As a result, future therapeutic strategies that aim to target M-CSF and its associated cytokines are proposed to mitigate inflammatory conditions, thus potentially decreasing the risk of adverse events related to atherosclerosis [49].…”

“…The differentiation and functions of hematopoietic progenitors in monocytes and macrophages are regulated by a cytokine known as M-CSF. It plays a crucial role in promoting the growth of these progenitors, inducing inflammation, and triggering tissue factor production, which leads to plaque instability and significantly contributes to the development of atherosclerosis [44][45][46].…”

“…It contributes to inflammation, which in turn leads to macrophage destruction and the progression of atherosclerosis. Furthermore, M-CSF triggers tissue factor production, which can result in plaque thrombosis and instability, which can lead to acute coronary syndrome [44]. Elevated levels of M-CSF have been observed in the bloodstream not only in cardiovascular diseases (CVDs) but also in various other diseases, such as tumors [45].…”