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.

This review aimed to trace the inflammatory pathway from the NLRP3 inflammasome to monomeric C-reactive protein (mCRP) in atherosclerotic cardiovascular disease. CRP is the final product of the interleukin (IL)-1β/IL-6/CRP axis. Its monomeric form can be produced at sites of local inflammation through the dissociation of pentameric CRP and, to some extent, local synthesis. mCRP has a distinct proinflammatory profile. In vitro and animal-model studies have suggested a role for mCRP in: platelet activation, adhesion, and aggregation; endothelial activation; leukocyte recruitment and polarization; foam-cell formation; and neovascularization. mCRP has been shown to deposit in atherosclerotic plaques and damaged tissues. In recent years, the first published papers have reported the development and application of mCRP assays. Principally, these studies demonstrated the feasibility of measuring mCRP levels. With recent advances in detection techniques and the introduction of first assays, mCRP-level measurement should become more accessible and widely used. To date, anti-inflammatory therapy in atherosclerosis has targeted the NLRP3 inflammasome and upstream links of the IL-1β/IL-6/CRP axis. Large clinical trials have provided sufficient evidence to support this strategy. However, few compounds target CRP. Studies on these agents are limited to animal models or small clinical trials.

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.

Atherosclerosis is a widespread cardiovascular disease characterized by retention of atherogenic lipoproteins in the arterial wall and the onset of subclinical vascular inflammation; the development of atherosclerotic plaques; eventual narrowing of the arterial lumen and/or plaque disruption; and subsequent manifestation with stable ischemia or acute atherothrombotic events. Numerous cell types are implicated in atherogenesis. Monocytes/macrophages are considered pivotal participants in this complex process. They play a crucial role in the onset and augmentation of inflammation and greatly contribute to atherosclerotic plaque growth and destabilization. However, monocytes/macrophages are also essential for the resolution of inflammation and the stabilization of atherosclerotic lesions. In this regard, studies of the function of monocytes/macrophages in relation to this disease are of considerable interest to researchers, as the results can help to design new drugs aimed at preventing the development of atherosclerosis and its complications. This review presents current data on the classification and functions of monocytes/macrophages; discusses current hypotheses regarding the involvement of monocytes/macrophages in atherogenesis; and highlights existing gaps in evidence. This review is primarily aimed at readers with a background in clinical medicine who are interested in the involvement of monocytes/macrophages in atherogenesis.

Fibrin monomer (FM) is a transient intermediate of blood coagulation that functions as both an active regulator of haemostasis and a sensitive biomarker for prothrombotic states. Clinically, FM is measured indirectly as its derivative, soluble fibrin monomer complexes (SFMC), which is also often referred to as FM throughout the clinical literature. FM participates in a complex regulatory network modulating thrombin generation and fibrinolysis, interacting with platelet receptors, including integrin αIIbβ3 and GPVI, and engaging GPIb-vWF interactions. This comprehensive review examines FM’s molecular mechanisms in haemostatic regulation and evaluates clinical evidence for FM as a biomarker. Particular focus is placed on FM’s utility for risk stratification across thrombotic conditions, including disseminated intravascular coagulation, venous thromboembolism, ischemic stroke, myocardial infarction, and COVID-19-associated coagulopathy. Current challenges, including assay standardization and universal cut-off values, are discussed. By synthesizing mechanistic insights with clinical data, this integrated perspective may accelerate the translation of FM biology into improved risk assessment tools and novel therapeutic strategies.