Altered elastase—alpha1-antitrypsin balance in the blood of patients with chronic venous disease

Budzyn-Napierala, M; Iskra, Maria; Krasiński, Zbigniew; Turkiewicz, Wojciech; Gryszczyńska, Bogna; Kasprzak, Magdalena Paulina; Urbanek, Tomasz

doi:10.1177/0268355515569559

Cited by 4 publications

(8 citation statements)

References 46 publications

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“…They believed that the LE-AAT balance might have turned in favor of antiprotease in the early stages of the disease. 12 However, Budzyn-Napierala et al did not observe a significant difference in LE concentrations between healthy volunteers and CVD patients. 12 Our study determined that AAT levels are similar in the early stages of the disease (CEAP 1-3), and decreased in the CEAP-4 group but increased again in the CEAP-5 group.…”

Section: Discussionmentioning

confidence: 91%

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The role of alpha-1-antitrypsin in the etiopathogenesis of chronic venous disease: A prospective clinical trial

et al. 2022

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Objective The study aimed to examine whether alpha-1-antitrypsin (AAT), an inhibitor of leukocyte esterase(LE), which damages the venous vessel wall, has a protective effect against chronic venous disease(CVD), and to examine the relationship between AAT levels and disease severity. Methods Patients admitted with varicose vein disease and having reflux flow lasting longer than 0.5 s as determined by Doppler ultrasound were included. The informed consents were taken, and blood samples were obtained for complete blood count, C-reactive protein (CRP) level, and AAT level following anamnesis and physical examination. Clinical Etiologic Anatomic Pathologic (CEAP) classification was used to assess disease severity, and patients were divided into CEAP 1–5 groups accordingly. Results A total of 87 patients were included in the study. There was no statistically significant difference between the groups in body weight, red blood cell counts, platelet counts, or neutrophil counts ( p = 0.117, p = 0.932, p = 0.177, and p = 0.177, respectively).CRP and AAT levels were higher in patients with a CEAP clinical score of 5 compared to the other groups ( p = 0.018, and p = 0.020, respectively). AAT levels were similar in the CEAP 1–3 group and decreased in the CEAP-4 group but increased again in the CEAP-5 group. The AAT level was 1.62 ± 0.3 g/L in the CEAP-1 group, 1.61 ± 0.21 g/L in the CEAP-2 group, 1.61 ± 0.27 g/L in the CEAP-3 group, 1.48 ± 0.28 g/L in the CEAP-4 group, and 1.94 ± 0.39 g/L in the CEAP-5 group. CRP levels and platelet counts were observed to affect AAT levels ( p = 0.10, p = 0.017, respectively). Conclusion We believe that our hypothesis that low AAT levels play a role in the etiopathogenesis of CVD has been partially validated, at least in the CEAP-4 group. However, we believe that increased AAT levels in the CEAP-5 group may be a reactive increase in increased LE levels due to higher CRP levels of this group.

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Section: Discussionmentioning

confidence: 91%

“…[9][10][11] Again, it is thought that this balance might also play a part in the etiopathogenesis of CVD. 12 Shields et al observed that LE activity increased in all clinical stages in CVD patients. 3 Similarly, Stvrtinova et al reported that LE activity increased in CVD patients.…”

Section: Discussionmentioning

confidence: 98%

The role of alpha-1-antitrypsin in the etiopathogenesis of chronic venous disease: A prospective clinical trial

et al. 2022

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“…The activity of LE is controlled by specific serine protease inhibitor, Alpha 1-Antitrypsin (AAT). Any imbalance between these two leads to local tissue inflammation and other pathological conditions, like cancer, inflammation in the vein [37] . It is well reported that increase in the level of neutrophil elastase was measured as a marker of neutrophil degranulation, which is well observed in varicose vein patients compared to age-matched control humans [38] .…”

Section: Resultsmentioning

confidence: 99%

Herbal Formulations Ameliorates Chronic Venous Insufficiency, Venotonicity and Elastase Inhibition in the Management of Varicose Veins: A Preclinical Study

Onkaramurthy¹,

Vishwakarma²,

Singh³

et al. 2022

IJPS

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Onkaramurthy et al.: Herbal Formulations for the Management of Varicose VeinsVaricose vein is one of the common vascular diseases, in which veins become widened, bulged and twisted. Development of drug to combat varicose vein is a challenging task due to complex nature of the disease and non-availability of specific animal model system. In this context, relevant experimental models were developed and polyherbal formulations HVVL-041702 a liniment intended for topical use (200 µl/ animal) and HVVT-041701 a granule intended for oral use (250 mg/kg body weight, orally) were evaluated. In vitro elastase inhibition assay was carried out using the human leukocyte elastase enzyme. Ex vivo venotonic activity was performed in isolated rat vena cava. In vivo anti-inflammatory, analgesic and anti-edemagenic activity were carried out in Wistar rats. Along with the aforementioned activities, HVVT-041701 was also evaluated for chronic venous insufficiency. Both the formulations showed elastase inhibition, venotonic, antiinflammatory, analgesic and anti-edemagenic activities. HVVT-041701 was also effective in ameliorating chronic venous insufficiency by decreasing the venous pressure. Both the formulations showed beneficial effects in the management of varicose veins by improving the tonicity, venous insufficiency and vascular hyper permeability which are the pathologic hallmark of varicose veins.

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“…In the present report we observed a significant difference in E-XDP in patients grouped according to increased clinical severity of CVD but the reason for the elevated E-XDP in these patients remains unknown. Besides activation of leukocytes, it is possible that the patients have thrombi in other parts of the body or micro thrombi in the vein wall that are also degraded by LE, but other unknown sources of thrombi can not be excluded [ 14 , 23 ]. For example, in a previous study by our group, we observed an association between E-XDP and presence of intraluminal thrombi in patients with abdominal aortic aneurysms [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…Patients with CVD have elevated levels of leucocyte elastase (LE) that is released upon activation of leucocytes [ 14 ]. This enzyme degrades cross-linked fibrin specifically, in sites different from those hydrolyzed by plasmin, producing fibrin degradation products known as E-XDP which are structurally different from D-dimers [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Plasma levels of leucocyte elastase-generated cross linked fibrin degradation products (E-XDP) are elevated in chronic venous disease

et al. 2021

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Patients with chronic venous disease (CVD) have elevated levels of leucocyte elastase (LE) released from the activation of leucocytes. In acute deep venous thrombosis (DVT), LE can degrade fibrin from the thrombus resulting in cross-linked fibrin degradation products (E-XDP) being released into the bloodstream. In patients with CVD the levels and significance of circulating E-XDP are unknown. We aimed to investigate the association between plasma E-XDP concentration and severity of CVD. Levels of E-XDP were quantified with a specific enzyme-linked immunosorbent assay (ELISA) in plasma from 142 consecutively recruited CVD patients (mean age 64 years, (range 23–89), 81 were females and 61 males). Patients were also divided into three groups based on CVD severity using the C-class of the Clinical-Etiological-Anatomical-Pathophysiological (CEAP) classification, with C 0–1 class as the reference group, C 2–3 as the second group and C 4–6 as the third group with the most severely affected patients. We found significantly elevated levels of E-XDP in patients with C 4–6 compared with patients with C 0–1 (p = 0.007) and increased with increasing disease severity across the groups (p = 0.02). Significant independent association was observed between levels of E-XDP and the classes C 4–6 after adjustment for age and sex (p < 0.05), but the association was no longer significant after further adjustment for use of statins, use of anticoagulants and history of DVT (p = 0.247). This exploratory study shows that E-XDP levels are elevated in patients with CVD, encouraging further studies on the role of E-XDP in CVD.

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Altered elastase—alpha1-antitrypsin balance in the blood of patients with chronic venous disease

Cited by 4 publications

References 46 publications

The role of alpha-1-antitrypsin in the etiopathogenesis of chronic venous disease: A prospective clinical trial

The role of alpha-1-antitrypsin in the etiopathogenesis of chronic venous disease: A prospective clinical trial

Herbal Formulations Ameliorates Chronic Venous Insufficiency, Venotonicity and Elastase Inhibition in the Management of Varicose Veins: A Preclinical Study

Plasma levels of leucocyte elastase-generated cross linked fibrin degradation products (E-XDP) are elevated in chronic venous disease

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