Circulating monocyte-platelet aggregates with different monocyte subsets and their association with disease severity in chronic kidney disease

Many studies have demonstrated a strong association between inflammation and the risk of atherosclerosis and future cardiovascular events in CKD. Patients with CKD, especially with end stage renal disease (ESRD) often suffer from endothelial cells damage, dysregulation of many inflammatory cytokines, the immune imbalance of T cells, and abnormal activation of monocytes and platelets. ^{, ,} Monocytes are crucially involved in practically all stages of CKD as the cellular drivers of immune inflammation. In addition to roles in thrombosis, platelets also present ability to influence the phenotype of other immune and vascular cells through cell-cell signaling, and play an important and central role in immune inflammation. Activated platelets promote monocytes arrest on the endothelium and enhance monocytes recruitment into developing atherosclerotic lesions.

Therefore, Interaction between platelets and monocytes is considered a crucial pathophysiological mechanism linking immune inflammation and atherosclerosis in the development of CKD.

Cross-talk between platelets and monocytes is reflected by formation monocyte-platelet aggregates (MPAs). Human monocytes are classified as classical (CD14++CD16−; CM), intermediate (CD14++CD16+; IM) and non-classical (CD14+CD16++; NCM) monocytes based on expression of the lipopolysaccharide (LPS) receptor (CD14) and the low-affinity Fc receptor III for IgG (CD16) on their cell surface.

^, Studies have shown that the potential significance of CD16+ monocytes have the strong binding affinity to the endothelium and participate in arteriosclerosis. On the other hand, CD14++CD16-monocytes are also reported to be increased in subjects with cardiovascular disease risk factors. Platelets can bind to three monocyte subsets which differ in functional properties. Several recent studies have found elevated MPAs levels in inflammatory diseases that are related to endothelial cell damage, such as coronary artery disease, aortic stenosis, unstable angina, and acute myocardial infarction, lung injury and ischemic stroke. MPAs initiate production of proinflammatory cytokine, expression of cell-adhesion molecules, and the release of matrix metalloproteinases, all of which may be important in atherosclerosis. Thus, MPAs simultaneously participates in the progress of immune inflammation and atherosclerosis that are both important processes closely related to progression of CKD. However, the relationship between the MPAs, especially MPAs with different monocyte subsets, and CKD has not been systematically evaluated. Therefore, the aim of this study was to investigate the circulating MPAs and examine changes of monocyte subsets in MPAs in CKD2-5 compared to healthy controls to determine if an altered distribution of in MPAs with different monocyte subsets is associated with the different stages and severity of CKD.