Biomarkers of inflammation and endothelial function: The holy grail of experimental and clinical medicine?

doi:10.1016/j.vph.2011.12.003

Vascular Pharmacology

Volume 56, Issues 1–2, January–February 2012, Pages 26-28

https://doi.org/10.1016/j.vph.2011.12.003 Get rights and content

Abstract

Drug induced vasculitides in humans are relatively rare diseases, resembling drug-induced vasculitis in rodents and primary idiopathic vasculitis. Because of their exquisite inflammatory nature, vascular lesions in these conditions release a large amount of bioactive molecules and activate multiple cell types, including endothelial cells, neutrophils, monocytes and T-lymphocytes, all of which might be in principle used as biomarkers of the underlying disease. Although each vasculitis may have specific features, the potential biomarkers released remain largely non-specific, raising the question of whether they represent a useful clinical tool. Low specificity, short half-lives and analytical weaknesses are all issues that must be resolved before such biomarkers can be routinely used as diagnostic tools in vasculitis. Further investigation of biomarkers in animal models may be key to a better understanding of their potential usefulness (graphical abstract figure).

Graphical abstract

The figure summarized the issues discussed in the review: human and rodent drug-induced vasculitides induce the release in the blood stream of a number of biomarkers, in part also present in atherosclerotic vascular diseases. The aim of current and future research will be to establish the analytical performance and specificity of these biomarkers in order to set a panel of them that may help in planning studies in humans and laboratory animals and improve diagnosis and prognostication in humans.

sE-selectin: soluble endothelial selectin; vWF: von Willebrand factor; MPO: myeloperoxidase; sPLA2: secretory phospholipase A2; Lp-PLA2: lipoprotein-associated phospholipase A2; VEGF: vascular endothelial growth factor; PIGF: placental growth factor; HGF: hepatocyte growth factor; MMPs: matrix metalloproteinases; PAPP-A: pregnancy-associated plasma peptide; sCD40L: soluble CD40 ligand; sP-selectin: soluble platelet selectin ; EMPs: endothelial microparticles; primary AAVs: associated small vessel vasculitis; DIVI: drug-induced vascular injury.

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The role of vascular inflammation markers in deficiency of adenosine deaminase 2
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Citation Excerpt :
Identifying the relevant mediators involved in the vascular inflammation and hematological outcome can improve our understanding of the pathogenesis and guide us in the management of DADA2 patients. Vascular inflammation markers, including sST2 (soluble suppression of tumorigenesis-2, interleukin 1 receptor like 1), sRAGE (soluble isoform of a receptor for advanced glycation end products), Tie-2 (tyrosine-protein kinase receptor), sCD40L (soluble CD40 ligand), Tie-1 (tyrosine-protein kinase receptor), sFlt-1 (soluble vascular endothelial growth factor receptor-1), LIGHT (tumor necrosis factor superfamily member 14), TNF-α (tumor necrosis factor alpha), PlGF (placental growth factor), IL-6 (interleukin-6), IL-18, IL-10, and MCP-1 (monocyte chemoattractant protein-1) have previously been studied in certain vasculitis and strokes [13–18]. In this study, we aimed to investigate the role of these markers in the vascular inflammation of DADA2 and compare the vascular inflammation profiles between patients with clear vasculitis phenotype, with a Diamond Blackfan-like phenotype of DADA2.
The first objective was to assess the role of vascular inflammatory factors in the pathogenesis of deficiency of adenosine deaminase 2 (DADA2) and to compare these markers among DADA2 patients with different phenotypes. We also aimed to investigate differences between DADA2 patients with vasculitic features and classic polyarteritis nodosa (PAN) for the aforementioned markers.
The study included eighteen DADA2 patients, ten PAN patients, and eight healthy controls. Plasma levels of sST2, sRAGE, Tie-2, sCD40L, Tie-1, sFlt-1, LIGHT, TNF-α, PlGF, IL-6, IL-18, IL-10, MCP-1 were studied by cytometric bead-based multiplex assay panel.
Among the DADA2 patients, five had hematological manifestations, 13 had vasculitic findings, and accompanying immunological findings were present in seven patients. Nine patients had neurological findings, five of whom had neuropathy. Plasma levels of Tie-1 and sFlt-1 were higher in the overall DADA2 patients compared to healthy controls and PAN patients (p<0.001 and p = 0.004, respectively). DADA2 patients with PAN-like features had higher sRAGE, Tie-2, and TNF-α levels compared to PAN patients (p = 0.013, p = 0.003, and p = 0.001, respectively).
In DADA2 patients with hematological findings, plasma IL-18 levels were higher than those with PAN-like phenotype (p = 0.001). Finally, DADA2 patients with neuropathy had higher sRAGE concentrations than patients without neuropathy and healthy controls (p = 0.03 and p = 0.008, respectively).
We suggest that the high plasma IL-18 levels observed in DADA2 patients with hematologic manifestations may be associated with an activated IFNγ pathway, and lack of response to anti-TNF treatment. We identified sRAGE as a potential biomarker of neuropathy in DADA2 patients. Higher concentrations of Tie-1, Tie-2, sFlt-1, sRAGE, and TNF-α distinguished DADA2 patients with PAN-like features from PAN patients.
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ReviewBiomarkers of inflammation and endothelial function: The holy grail of experimental and clinical medicine?

Abstract

Graphical abstract

Assessment of the multiple-biomarker approach for diagnosis of myocardial infarction in patients presenting with symptoms suggestive of acute coronary syndrome

Clin. Chem.

Contribution of 30 biomarkers to 10-year cardiovascular risk estimation in 2 population cohorts: the MONICA, risk, genetics, archiving, and monograph (MORGAM) biomarker project

Circulation

Microparticles and microRNAs: new players in the complex field of coagulation

Intern. Emerg. Med.

Drug-induced illness leading to hospitalization

JAMA

Review
Biomarkers of inflammation and endothelial function: The holy grail of experimental and clinical medicine?