The von Willebrand factor (vWF) is a plasma protein that mediates platelet adhesion and leukocyte recruitment to vascular injury sites and carries coagulation factor VIII, a building block of the intrinsic pathway of coagulation. The presence of ultra-large multimers of vWF in the bloodstream is associated with spontaneous thrombosis, whereas its deficiency leads to bleeding. In cardiovascular pathology, the progression of the heart valve disease results in vWF deficiency and cryptogenic gastrointestinal bleeding. The association between higher plasma levels of vWF and thrombotic complications of coronary artery disease was described. Of note, it is not the plasma levels that are crucial for vWF hemostatic activity, but vWF activation, triggered by a rise in shear rates. vWF becomes highly reactive with platelets upon unfolding into a stretched conformation, at shear rates above the critical value (more than 5000 s−1), which might occur at sites of arterial stenosis and injury. The activation of vWF and its counterbalance by ADAMTS-13, the vWF-cleaving protease, might contribute to complications of cardiovascular diseases. In this review, we discuss vWF involvement in complications of cardiovascular diseases and possible diagnostic and treatment approaches.

C-reactive Protein (CRP) is an acute phase reactant, belonging to the pentraxin family of proteins. Its level rises up to 1000-fold in response to acute inflammation. High sensitivity CRP level is utilized as an independent biomarker of inflammation and cardiovascular disease. The accumulating data suggests that CRP has two distinct forms. It is predominantly produced in the liver in a native pentameric form (nCRP). At sites of local inflammation and tissue injury it may bind to phosphocholine-rich membranes of activated and apoptotic cells and their microparticles, undergoing irreversible dissociation to five monomeric subunits, termed monomeric CRP (mCRP). Through dissociation, CRP deposits into tissues and acquires distinct proinflammatory properties. It activates both classic and alternative complement pathways, binding complement component C1q and factor H. mCRP actively participates in the development of endothelial dysfunction. It activates leukocytes, inducing cytokine release and monocyte recruitment. It may also play a role in the polarization of monocytes and T cells into proinflammatory phenotypes. It may be involved in low-density lipoproteins (LDL) opsonization and uptake by macrophages. mCRP deposits were detected in samples of atherosclerotic lesions from human aorta, carotid, coronary and femoral arteries. mCRP may also induce platelet aggregation and thrombus formation, thus contributing in multiple ways in the development of atherosclerosis and atherothrombosis. In this mini-review, we will provide an insight into the process of conformational rearrangement of nCRP, leading to dissociation, and describe known effects of mCRP. We will provide a rationalization for mCRP involvement in the development of atherosclerosis and atherothrombosis.

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.

The purpose of the study was to assess whether the occurrence of restenosis is associated with CD45þ platelet count and neutrophil to lymphocyte ratio in patients with type 2 diabetes mellitus (DM) after drug-eluting stent (DES) implantation for stable coronary artery disease (CAD). The study comprised 126 patients, including 55 patients with type 2 DM and stable CAD who underwent elective coronary artery stenting with DES and follow-up angiography within 6 to 12 months. Blood samples were collected from each patient on the morning of the coronary angiography procedure. The variables related to in-stent restenosis were selected by logistic regression analysis. The logistic regression analysis showed that 2 inflammatory factors, CD45þ platelet count (odds ratio [OR] ¼ 4.51, 95% confidence interval [CI]: 1.50-13.50, P ¼ .007) and neutrophil to lymphocyte ratio (OR ¼ 3.09, 95% CI: 1.05-9.10, P ¼ .04), were significantly associated with the risk of in-stent restenosis after stenting with DES in patients with stable CAD and type 2 DM. A receiver operator characteristic curve analysis indicated that the area under the curve was 0.83% (0.05%; P < .001), which showed that the logistic model had good predictive accuracy (based on CD45þ platelet count and neutrophil to lymphocyte ratio) for the risk of in-stent restenosis development in DES in patients with CAD and type 2 DM. Two novel biomarkers of restenosis, CD45þ platelet count and neutrophil to lymphocyte ratio, may be effectively used to predict in-stent restenosis after DES implantation in patients with CAD and type 2 DM.

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The acquired data indicate the presence of a close relationship between circulating CD45+ platelets and restenosis development after DES implantation in patients with stable CAD.

Background. To assess structural and functional status of the arteries in young and middle-aged men with recently developed CAD. Methods and Results. A total of 78 men aged 28 to 50 years underwent carotid ultrasound, endothelial function, and arterial stiffness measurements. Angiographically proven CAD was present in 49 patients. Carotid plaques were present in 45 (91.8%) patients with CAD and in 8 (27.6%) men without CAD (P < 0.001). Patients with CAD more often had multiple plaques (86.7% versus 13.8%, P < 0.001). The prevalence of carotid intima-media thickness (IMT) ≥0.9 mm and of abnormal brachial artery flow-mediated dilatation (FMD) was not differing in both groups. The mean aortic pulse wave velocity (PWV) was 6.8 ± 1.3 m/s for patients with CAD and 5.8 ± 0.9 m/s for subjects without CAD (P < 0.001). Aortic PWV above the 75th percentile of the “normal” samples was found in 26 (53.1%) patients with CAD and in 7 (24.1%) subjects without CAD (P = 0.02). Aortic PWV was related to the severity of CAD. Conclusions. Carotid plaques and increased aortic PWV may be more powerful predictors of the occurrence of CAD in young and middle-aged men, than the presence of increased carotid IMT and abnormal brachial artery FMD.

The aim of this study was to assess the involvement of eosinophil cationic protein, a marker of eosinophil activation, in the development of in-stent restenosis after drug-eluting stent implantation. Follow-up angiography at 6 to 12 months was performed in 32 patients who were treated with percutaneous coronary intervention and implantation of sirolimus-eluting stents. Blood plasma levels of eosinophil cationic protein (ECP) and total immunoglobulin E (IgE) were measured by enzyme-linked immunosorbent assay and the level of C-reactive protein (hs-CRP) by high-sensitivity nephelometry. According to angiography data, in-stent restenosis occurred in 13 patients, while 19 patients did not develop it. There were no differences between the hs-CRP and IgE levels in patients with or without restenosis. In contrast, ECP level was higher in patients with restenosis compared with that in patients without restenosis [17.7 ng/mL (11.2-24.0) vs. 9.0 ng/mL (6.4-12.9), p = 0.017]. The incidence of in-stent restenoses was 63% in patients with ECP level higher than or equal to 11 ng/mL, and 19% in patients with an ECP level lower than 11 ng/mL (p = 0.019). These findings suggest that elevated eosinophil activation may play an important role in the pathogenesis of in-stent restenosis after implantation of drug-eluting stents.