Circulating Biomarkers in Lower Extremity Artery Disease

Ziegler, Louise; Hedin, Ulf; Gottsäter, Anders

doi:10.15420/ecr.2021.58

Cited by 9 publications

(5 citation statements)

References 132 publications

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“…PAD is often accompanied by a prothrombotic state [ 60 ]. Plasminogen activator inhibitor-1 (PAI-1) levels were higher both at rest and after exercise in PAD patients compared with healthy subjects [ 61 ].…”

Section: Procoagulant and Fibrinolytic Markers Of Padmentioning

confidence: 99%

Inflammatory and Prothrombotic Biomarkers, DNA Polymorphisms, MicroRNAs and Personalized Medicine for Patients with Peripheral Arterial Disease

Poredoš

Šabovič

Mijovski

et al. 2022

IJMS

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Classical risk factors play a major role in the initiation and development of atherosclerosis. However, the estimation of risk for cardiovascular events based only on risk factors is often insufficient. Efforts have been made to identify biomarkers that indicate ongoing atherosclerosis. Among important circulating biomarkers associated with peripheral arterial disease (PAD) are inflammatory markers which are determined by the expression of different genes and epigenetic processes. Among these proinflammatory molecules, interleukin-6, C-reactive protein, several adhesion molecules, CD40 ligand, osteoprotegerin and others are associated with the presence and progression of PAD. Additionally, several circulating prothrombotic markers have a predictive value in PAD. Genetic polymorphisms significantly, albeit moderately, affect risk factors for PAD via altered lipoprotein metabolism, diabetes, arterial hypertension, smoking, inflammation and thrombosis. However, most of the risk variants for PAD are located in noncoding regions of the genome and their influence on gene expression remains to be explored. MicroRNAs (miRNAs) are single-stranded, noncoding RNAs that modulate gene expression at the post-transcriptional level. Patterns of miRNA expression, to some extent, vary in different atherosclerotic cardiovascular diseases. miRNAs appear to be useful in the detection of PAD and the prediction of progression and revascularization outcomes. In conclusion, taking into account one’s predisposition to PAD, i.e., DNA polymorphisms and miRNAs, together with circulating inflammatory and coagulation markers, holds promise for more accurate prediction models and personalized therapeutic options.

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Section: Procoagulant and Fibrinolytic Markers Of Padmentioning

confidence: 99%

Inflammatory and Prothrombotic Biomarkers, DNA Polymorphisms, MicroRNAs and Personalized Medicine for Patients with Peripheral Arterial Disease

Poredoš

Šabovič

Mijovski

et al. 2022

IJMS

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show abstract

“…However, as Ziegler et al report in this collection, biomarkers mirroring inflammation, lipid metabolism and coagulation associate with prognosis and to a certain extent may predict the risk of LEAD. [ 8 ] In particular, in line with the results from clinical trials, Mendelian randomisation studies indicate hypercoagulability as a causal factor in the development of LEAD. [ 9 ] The diagnosis of LEAD is mainly based on clinical evaluation of patients and the assessment of circulating biomarkers may improve our understanding of its pathophysiology and identify patients who would benefit from medical treatment.…”

mentioning

confidence: 77%

Present and Future Perspectives on the Role of Biomarkers in Atherosclerotic Cardiovascular Disease Risk Stratification

Gigante

2023

Eur Cardiol

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“…The diagnosis currently rests on clinical tests followed by invasive imaging procedures, and circulating biomarkers of endothelial dysfunction or inflammation may give additional information. These include inflammatory cell types, such as monocytes [ 31 ], or cytokines, such as TNFα and IL6, and acute-phase reactants like CRP, as well as markers of endothelial activation, such as VCAM1 and other adhesion molecules, reviewed in [ 32 ]. However, they are often unspecific and not used in clinical routine.…”

Section: Discussionmentioning

confidence: 99%

Circulating Soluble EPCR Levels Are Reduced in Patients with Ischemic Peripheral Artery Disease and Associated with Markers of Endothelial and Vascular Function

Krug,

Bochenek,

Gogiraju

et al. 2023

Biomedicines

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(1) Background: Endothelial dysfunction initiates cardiovascular pathologies, including peripheral artery disease (PAD). The pathophysiology of impaired new vessel formation in the presence of angiogenic stimuli, such as ischemia and inflammation, is unknown. We have recently shown in mice that reduced endothelial protein C receptor (EPCR) expression results in defective angiogenesis following experimental hindlimb ischemia. (2) Purpose: To determine soluble (s)EPCR levels in the plasma of patients with PAD and to compare them with the protein C activity and biomarkers of endothelial function, inflammation, and angiogenesis. (3) Methods and Results: Clinical tests of vascular function and immunoassays of plasma from patients with PAD stage II were compared to age- and sex-matched individuals with and without cardiovascular risk factors or PAD stage III/IV patients. sEPCR levels were significantly lower in PAD stage II patients compared to subjects with risk factors, but no PAD, and further decreased in PAD stage III/IV patients. Plasma protein C activity or levels of ADAM17, a mediator of EPCR shedding, did not differ. Significant associations between sEPCR and the ankle-brachial index (p = 0.0359), age (p = 0.0488), body mass index (p = 0.0110), and plasma sE-selectin levels (p = 0.0327) were observed. High-sensitive CRP levels and white blood cell counts were significantly elevated in PAD patients and associated with serum glucose levels, but not sEPCR. In contrast, plasma TNFα or IL1β levels did not differ. Circulating levels of VEGF were significantly elevated in PAD stage II patients (p = 0.0198), but not associated with molecular (sE-selectin) or functional (ankle-brachial index) markers of vascular health. (4) Conclusions: Our findings suggest that circulating sEPCR levels may be useful as biomarkers of endothelial dysfunction, including angiogenesis, in persons older than 35 years and that progressive loss of endothelial protein C receptors might be involved in the development and progression of PAD.

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Circulating Biomarkers in Lower Extremity Artery Disease

Cited by 9 publications

References 132 publications

Inflammatory and Prothrombotic Biomarkers, DNA Polymorphisms, MicroRNAs and Personalized Medicine for Patients with Peripheral Arterial Disease

Inflammatory and Prothrombotic Biomarkers, DNA Polymorphisms, MicroRNAs and Personalized Medicine for Patients with Peripheral Arterial Disease

Present and Future Perspectives on the Role of Biomarkers in Atherosclerotic Cardiovascular Disease Risk Stratification

Circulating Soluble EPCR Levels Are Reduced in Patients with Ischemic Peripheral Artery Disease and Associated with Markers of Endothelial and Vascular Function

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