Circulating annexin A5 levels are associated with carotid intima-media thickness but not coronary plaque composition

Burgmaier, Mathias; Reith, Sebastian; Schurgers, Leon J.; Kahles, Florian; Reutelingsperger, Chris

doi:10.1177/1479164117710392

Cited by 4 publications

(4 citation statements)

References 31 publications

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“…The relationship of endogenous ANXA5 with atherosclerotic complications is not well defined. While the levels of circulating ANXA5 have been shown to be associated with the severity of coronary stenosis [ 46 ] and subclinical atherosclerosis outcomes in patients with T2DM or systemic lupus erythematosus [ 33 , 47 ], another study revealed no direct association between ANXA5 levels and CIMT progression [ 30 ], consistent with the present study. The differences between all the above reported studies could be related to study design, population sample size, and/or the nature and progression of disease among patients.…”

Section: Discussionsupporting

confidence: 88%

“…In this study, we found that levels of circulating sF11R were notably higher than previously reported values for hemodialysis, hypertensive, and patients with normal or nonobstructive disease, suggesting a role of sF11R in the pathophysiology of diabetes [ 18 , 19 , 29 ]. While, several studies reported abnormal elevations of circulating ANXA5 in familial hypercholesterolemia, hypertensive patients, and patients with myocardial infarction [ 30 , 31 , 32 ], levels of ANXA5 among the patients of current study were within normal range (0–2 ng/mL), similar to those reported in healthy population [ 24 , 33 ]. Interestingly, we found that sF11R levels correlated positively with ANXA5 levels.…”

Section: Discussionsupporting

confidence: 83%

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Relationship between the Soluble F11 Receptor and Annexin A5 in African Americans Patients with Type-2 Diabetes Mellitus

et al. 2022

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Type 2 diabetes mellitus (T2DM) is characterized by endothelial dysfunction, increased thrombogenicity, and inflammation. The soluble human F11 receptor (sF11R) and annexin A5 (ANXA5) play crucial roles in inflammatory thrombosis and atherosclerosis. We examined the relationship between circulating sF11R and ANXA5 and their impact on endothelial function. The study included 125 patients with T2DM. Plasma levels of sF11R and ANXA5 were quantified by ELISA. Microvascular function was assessed using the vascular reactivity index (VRI). Large artery stiffness was assessed by carotid-femoral pulse wave velocity (PWV). Carotid intima-media thickness (CIMT) was assessed by B-mode ultrasound imaging. The mean age of patients in the study was 59.7 ± 7.8 years, 78% had hypertension, 76% had dyslipidemia, and 12% had CKD. sF11R correlated positively with ANXA5 levels (β = 0.250, p = 0.005), and correlated inversely with VRI and total nitic oxide (NO), (β = −0.201, p = 0.024; β = −0.357, p = 0.0001, respectively). Multivariate regression analysis revealed that sF11R was independently associated with ANXA5 in the total population and in patients with HbA1c > 6.5% (β = 0.366, p = 0.007; β = 0.425, p = 0.0001, respectively). sF11R and ANXA5 were not associated with vascular outcome, suggesting that they may not be reliable markers of vascular dysfunction in diabetes. The clinical significance of sF11R/ANXA5 association in diabetes warrants further investigation in a larger population.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 83%

Relationship between the Soluble F11 Receptor and Annexin A5 in African Americans Patients with Type-2 Diabetes Mellitus

et al. 2022

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“…Endogenous annexin A5 in all treatment groups was similar to the normal basal circulating plasma levels of healthy volunteers (Matsuda et al, 2003;Van Heerde et al, 2003;Burgmaier et al, 2017). Plasma SY-005 concentrations were obtained by subtracting endogenous levels from total annexin A5 concentrations.…”

Section: Discussionmentioning

confidence: 74%

Pharmacokinetics of recombinant human annexin A5 (SY-005) in patients with severe COVID-19

Tschirhart,

Lu,

Mokale Kognou

et al. 2024

Front. Pharmacol.

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Objective: Annexin A5 is a phosphatidylserine binding protein with anti-inflammatory, anticoagulant and anti-apoptotic properties. Preclinical studies have shown that annexin A5 inhibits pro-inflammatory responses and improves organ function and survival in rodent models of sepsis. This clinical trial aimed to evaluate the pharmacokinetic (PK) properties of the recombinant human annexin A5 (SY-005) in severe COVID-19.Methods: This was a pilot randomized, double-blind, placebo-controlled trial. Severe COVID-19 patients were randomly assigned to receive intravenous 50 μg/kg (low dose, n = 3), 100 μg/kg (high dose, n = 5) of SY-005 or placebo (n = 5) every 12 h for 7 days. Plasma SY-005 levels were assessed using enzyme-linked immunosorbent assay (ELISA) and the PK parameters were determined using non-compartmental analysis.Results: All patients treated with SY-005 had a normal baseline estimated glomerular filtration rate (eGFR, 104–125 mL/min/1.73 m2). Both low and high doses of SY-005 were cleared within 6 h after intravenous administration. Plasma maximum concentrations (Cmax), half-life, clearance and volume distribution of low and high doses of SY-005 were 402.4 and 848.9 ng/mL, 0.92 and 0.96 h, 7.52 and 15.19 L/h, and 9.98 and 20.79 L, respectively. Daily pre-dose circulating annexin A5 levels were not significantly different when SY-005 was administered at the low or the high dose 12-h intervals. There was no significant effect on activated partial thromboplastin time (aPTT) or INR (international normalized ratio of prothrombin time) during 7 days of SY-005 treatment.Conclusion: SY-005 doses of 50 and 100 μg/kg were detectable and subsequently cleared from the plasma in severe COVID-19 patients with normal baseline renal function. There was no significant plasma SY-005 accumulation 6 h after drug administration and coagulation was not altered during 7 days of treatment.Clinical trials Registration: This study was registered with ClinicalTrials.gov (NCT04748757, first posted on 10 February 2021).

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“…However, the role of ANXA5 in CAD remains controversial. Burgmaier et al revealed that in high-risk diabetic patients, the level of circulating ANXA5 correlated with the thickness of the carotid intima, but not with the composition of the coronary plaque ( Burgmaier et al, 2017 ). And Hashemi et al reported that the frequency of polymorphism in ANXA5 gene was not relevant to the presence of in-stent restenosis ( Hashemi et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Study on the mechanism of action of colchicine in the treatment of coronary artery disease based on network pharmacology and molecular docking technology

Liu

Yin

et al. 2023

Front. Pharmacol.

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Objective: This is the first study to explore the mechanism of colchicine in treating coronary artery disease using network pharmacology and molecular docking technology, aiming to predict the key targets and main approaches of colchicine in treating coronary artery disease. It is expected to provide new ideas for research on disease mechanism and drug development.Methods: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Swiss Target Prediction and PharmMapper databases were used to obtain drug targets. GeneCards, Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), DrugBank and DisGeNET databases were utilized to gain disease targets. The intersection of the two was taken to access the intersection targets of colchicine for the treatment of coronary artery disease. The Sting database was employed to analyze the protein-protein interaction network. Gene Ontology (GO) functional enrichment analysis was performed using Webgestalt database. Reactom database was applied for Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Molecular docking was simulated using AutoDock 4.2.6 and PyMOL2.4 software.Results: A total of 70 intersecting targets of colchicine for the treatment of coronary artery disease were obtained, and there were interactions among 50 targets. GO functional enrichment analysis yielded 13 biological processes, 18 cellular components and 16 molecular functions. 549 signaling pathways were obtained by KEGG enrichment analysis. The molecular docking results of key targets were generally good.Conclusion: Colchicine may treat coronary artery disease through targets such as Cytochrome c (CYCS), Myeloperoxidase (MPO) and Histone deacetylase 1 (HDAC1). The mechanism of action may be related to the cellular response to chemical stimulus and p75NTR-mediated negative regulation of cell cycle by SC1, which is valuable for further research exploration. However, this research still needs to be verified by experiments. Future research will explore new drugs for treating coronary artery disease from these targets.

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Circulating annexin A5 levels are associated with carotid intima-media thickness but not coronary plaque composition

Cited by 4 publications

References 31 publications

Relationship between the Soluble F11 Receptor and Annexin A5 in African Americans Patients with Type-2 Diabetes Mellitus

Relationship between the Soluble F11 Receptor and Annexin A5 in African Americans Patients with Type-2 Diabetes Mellitus

Pharmacokinetics of recombinant human annexin A5 (SY-005) in patients with severe COVID-19

Study on the mechanism of action of colchicine in the treatment of coronary artery disease based on network pharmacology and molecular docking technology

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