CRP Is Transported by Monocytes and Monocyte-Derived Exosomes in the Blood of Patients with Coronary Artery Disease

Abstract

The objective of this work was to study the ability of blood cells and their microparticles to transport monomeric and pentameric forms of C-reactive protein (mCRP and pCRP) in the blood of patients with coronary artery disease (CAD). Blood was obtained from 14 patients with CAD 46 ± 13 years old and 8 healthy volunteers 49 ± 13.6 years old. Blood cells and microparticles with mCRP and pCRP on their surface were detected by flow cytometry. Messenger RNA (mRNA) of CRP was extracted from peripheral blood monocytes stimulated with lipopolysaccharide (LPS) and granulocyte-macrophage colony-stimulating factor (GM-CSF). mRNA of CRP in monocytes was detected with PCR. Monocytes were predominantly pCRP-positive (92.9 ± 6.8%). mCRP was present on 22.0 ± 9.6% of monocyte-derived exosomes. mCRP-positive leukocyte-derived microparticle counts were significantly higher (8764 ± 2876/µL) in the blood of patients with CAD than in healthy volunteers (1472 ± 307/µL). LPS and GM-CSF stimulated monocytes expressed CRP mRNA transcripts levels (0.79 ± 0.73-fold), slightly lower relative to unstimulated hepatocytes of the HepG2 cell line (1.0 ± 0.6-fold), but still detectable. The ability of monocytes to transport pCRP in blood flow, and monocyte-derived exosomes to transmit mCRP, may contribute to the maintenance of chronic inflammation in CAD.

Monocyte Distribution Width As A Novel Sepsis Indicator in COVID-19 Patients

“…[28][29] Moreover, it was reported that monocytes can transport CRP in blood ow through monocyte-derived exosomes to maintain chronic in ammation. 30 The ndings of the current study presented signi cant negative correlation between MDW and total platelet (r=-0.140, p < 0.05).…”

Circulating Extracellular Vesicles As Biomarkers and Drug Delivery Vehicles in Cardiovascular Diseases

“…Plasma levels of the leukocyte-derived EVs were elevated in patients with hypertension and hyperlipidemia [ 51 ]. Melnikov et al [ 52 ] identified monocytes-derived EVs carrying monomeric C-reactive protein (mCRP) in the blood that was associated with inflammatory status in CAD patients.…”

“…Serum EV proteins, such as cystatin C, polygenic immunoglobulin receptor (pIgR) and complement factor C5a (C5a), were suggested to be associated with ACS [ 117 , 140 ]. mCRP carried by monocyte-derived EVs was associated with inflammatory process in patients with CAD [ 52 ]. EVs can transport and delivery pro-inflammatory mCRP in endothelial cells [ 118 ].…”

Antibody Protection against Long-Term Memory Loss Induced by Monomeric C-Reactive Protein in a Mouse Model of Dementia

“…An unbound fraction of mCRP has also recently been reported in serum of patients with high levels of circulating native CRP (>100 mg/L, in the range of acute inflammatory response), although the dissociation site of origin is unclear [19]. Furthermore, mCRP has been detected in U937-derived macrophages [20] and exosomes derived from monocytes of patients with coronary artery disease [21]. Additionally, other cell types such as neurons in the AD brain may produce CRP, albeit in lower amounts than hepatocytes [22].…”