Leukocyte–platelet aggregates—a phenotypic characterization of different stages of peripheral arterial disease

Abstract

The formation of monocyte-platelet aggregates and neutrophil-platelet aggregates (MPA and NPA, respectively) is influenced by inflammation, but also might contribute to an exacerbation of inflammatory responses in atherosclerotic plaque. The purpose of this study was to analyze MPA and NPA proportions in regard to different stages of peripheral arterial disease (PAD). Forty-five patients with intermittent claudication (IC) (3 groups: Rutherford (R)-1, R-2, and R-3; each n = 15), 20 patients with critical limb ischemia (CLI) (Rutherford 5 (40%) and 6 (60%)), and 20 healthy controls were studied. Analyses of monocyte (Mon) subpopulations (CD14++CD16- (classical) Mon1, CD14++CD16+ (intermediate) Mon2, CD14+CD16++ (non-classical) Mon3), MPA, and NPA was performed from whole blood by flow cytometry. Controls showed an increased proportion of the Mon1 subpopulation (p < 0.001), whereas CLI patients showed a significant increase of the Mon2 subpopulation compared to controls, R-1, or R-2 patients (p < 0.0001). For the Mon3 subpopulation, CLI and R-3 patients showed an increased proportion (p < 0.05). MPA formation with the proinflammatory Mon2 and Mon3 subpopulations was increased in CLI patients (both p < 0.01). Similarly, NPA was significantly increased in CLI patients (p < 0.05). Serological markers of inflammation and procoagulation (fibrinogen [r = 0.459, p < 0.001], soluble triggering receptor expressed on myeloid cells (sTREM-1) [r = 0.237, p < 0.05] and P-Selectin [r = 0.225, p < 0.05]) correlated directly with MPA formation on the Mon2 subpopulation. We found an association of inflammatory and procoagulatory markers with increased formation of MPA on the Mon2 subpopulation. Since R-3 patients also had significantly increased MPA, one can speculate that the inflammatory burden might promote an aggravation of the disease.

Effects of a novel hydrogen sulfide prodrug in a porcine model of acute limb ischemia

“…PAD patients experience profound vascular pathology that ultimately impacts vascular integrity and endothelial function from reduced NO bioavailability and deficient arteriolization with abnormal microvessel structure within the ischemic limb (16)(17)(18). Our laboratory has published data demonstrating significant reductions in circulating NO bioavailability in swine with CLI (19).…”

Changes in Blood Factors and Ultrasound Findings in Mild Cognitive Impairment and Dementia

“…Recent clinical investigations have focused on the relationship between levels of circulating adhesion factors in peripheral blood and cerebrovascular diseases (Vermeer et al, 2003 ; Dearborn et al, 2017 ). Platelets and leukocytes play a major role in atherothrombosis, aggregates of which result in the formation of atherosclerotic plaque (Folsom et al, 2009 ; Lievens et al, 2010 ; Dopheide et al, 2016 ; Gerdes et al, 2016 ). Although other factors associated with vascular disease can influence cognitive state, few studies have utilized flow cytometry to investigate platelet and leukocyte markers in older adults with cognitive decline.…”

Linarin prevents LPS‑induced acute lung injury by suppressing oxidative stress and inflammation via inhibition of TXNIP/NLRP3 and NF‑κB pathways

“…NPAs are formed in the lung microcirculation and rise in blood and alveolar compartments after injury ( 33 ). Thus, circulating leukocyte-platelet aggregates are a marker of platelet activation, and has been reported in patients with inflammatory conditions, such as sepsis, rheumatoid arthritis, coronary diseases, cystic fibrosis, inflammatory bowel disease and acute respiratory distress syndrome ( 34 ). Thromboxane A2, an indicator of platelet activation, is rapidly hydrolyzed to the inactive stable metabolite, TXB2 ( 24 ).…”