Increased concentrations of platelet- and endothelial-derived microparticles in patients with myocardial infarction and reduced renal function- a descriptive study

Abstract

Background Patients with chronic kidney disease (CKD) have a high risk of recurring thrombotic events following acute myocardial infarction (AMI). Microparticles (MPs) are circulating small vesicles shed from various cells. Platelet microparticles (PMPs) reflect platelet activation and endothelial microparticles (EMPs) reflect endothelial activation or dysfunction. Both increase following AMI, and may mediate important biological effects. We hypothesized that AMI patients with CKD have further elevated PMPs and EMPs compared with non-CKD patients, despite concurrent antithrombotic treatment. Methods We performed a descriptive study of patients with AMI. Fasting blood samples were acquired from 47 patients on dual antiplatelet treatment. Patients were stratified by renal function: normal (H; n = 19) mean eGFR 88; moderate CKD (CKD3; n = 15) mean eGFR 47, and severe CKD (CKD4–5; n = 13) mean eGFR 20 mL/min/1.73 m 2 . MPs were measured by flow-cytometry and phenotyped according to size (< 1.0 μm) and expression of CD41 (GPIIb; PMPs) and CD62E (E-selectin; EMPs). In addition, expression of platelet activation markers P-selectin (CD62P) and CD40ligand (CD154) were also investigated. Results PMPs expressing CD40 ligand were higher in CKD4–5: 210 /μl (174–237); median and interquartile range; vs. group H; 101 /μl (71–134; p < 0.0001) and CKD 3: 142 /μl (125–187; p = 0.006). PMPs expressing P-selectin were higher in CKD4–5 compared with H, but not in CKD3. EMPs were higher in CKD4–5; 245 /μl (189–308) compared with H; 83 /μl (53–140; p < 0.0001) and CKD3; 197 /μl (120–245; p < 0.002). Conclusions In AMI patients, PMPs and EMPs from activated platelets and endothelial cell are further elevated in CKD patients. This indicate impaired endothelial function and higher platelet activation in CKD patients, despite concurrent antiplatelet treatment.

An extracellular vesicle epitope profile is associated with acute myocardial infarction

“…They also correlated positively to peak hs‐troponin levels and inversely to LVEF, suggesting a direct correlation to injury severity. These findings are in general agreement with previous data showing increased numbers of platelet‐ and endothelial‐derived EVs in patients with ACS, possibly reflecting the formation of coronary thrombotic occlusions, compared to patients with chronic CAD and healthy individuals 12‐23 . We also found an increase in SSEA‐4, an antigen expressed by ‘very‐small embryonic‐like stem cells’ that are mobilized from bone marrow after cardiac ischemia and participate in endothelial repair, 33 at 24‐48 hours in STEMI patients.…”

“…Most circulating EVs in healthy individuals are derived from platelets and erythrocytes; however, vesicles also are released from leucocytes, endothelial cells, monocytes, neutrophils and lymphocytes 7,11 . Previous studies have shown increased numbers of platelet, endothelial cell‐ and leucocyte‐derived EVs in patients with acute coronary syndromes (ACS) or chronic CAD 12‐23 . However, partially divergent results have been reported, in part due to methodological differences in EV isolation 24,25 .…”

CD40/CD40L Signaling as a Promising Therapeutic Target for the Treatment of Renal Disease

“…Concentration of CD40 ligand + PMPs is positively associated with severity of CKD and inversely correlated with eGFR [35] Circulating sCD40L and sCD40…”

“…Platelet-derived microparticles (PMPs) are the most abundant microparticles in circulation and increased PMPs are associated with diabetes mellitus, myocardial infarction, and CKD [31][32][33][34]. Mörtberg and colleagues have recently shown that circulating concentrations of PMPs expressing CD40 ligand were positively associated with the severity of chronic kidney disease, and the concentration of CD40 ligand + PMPs is inversely correlated with estimated glomerular filtration rate (eGFR) [35]. In other studies, CD40 ligand + PMPs of CKD patients can be reduced by the vitamin D2 derivative, paricalcitol [36], or lipid-lowering treatment (LLT) with simvastatin in the settings of diabetes mellitus (DM)-CKD [34].…”

How do Uremic Toxins Affect the Endothelium?

“…In uremic conditions, it was demonstrated that PCS, IS, and inorganic phosphate induced the formation of EMPs from endothelial cells [ 113 , 163 , 167 , 168 , 169 ]. Studies have also shown that EMPs are related to endothelial dysfunction in CKD patients [ 17 , 167 , 170 , 171 ]. In vitro, Carmona et al [ 163 ] showed that EMPs from endothelial cells exposed to IS had increased levels of ICAM-1 and PECAM-1, and miRNAs (e.g., miR-181a-5p, miR-4454, and miR-150-5p).…”