Serum high mobility group box-1 and osteoprotegerin levels are associated with peripheral arterial disease and critical limb ischemia in type 2 diabetic subjects

Giovannini, Silvia; Tinelli, Giovanni; Biscetti, Federico; Straface, Giuseppe; Angelini, Flavia; Pitocco, Dario; Mucci, Luciana; Landolfi, Raffaele; Flex, Andrea

doi:10.1186/s12933-017-0581-z

Cited by 59 publications

(58 citation statements)

References 54 publications

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“…An earlier report demonstrated that the concentration of plasma HMGB-1 increased in patients with PAD than in healthy controls [92]. This notion was strongly supported by a recent study showing higher serum HMGB-1 levels in patients with type 2 diabetes affected by PAD [93]. Furthermore, the expression of HMGB-1 increased in diabetic foot atherogenesis and arteriosclerosis obliterans [94,95].…”

Section: Figsupporting

confidence: 74%

Emerging Role of High Mobility Group Box-1 in Thrombosis-Related Diseases

Pei

et al. 2018

Cell Physiol Biochem

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High mobility group box-1 (HMGB-1), a typical damage-associated molecular pattern protein released from various cells, was first identified in 1973. It is usually stored in the nuclei of cells. Several modifications of HMGB-1 promote its translocation to the cytosol, and it is actively or passively released from cells. When outside of the cells, HMGB-1is crucial in inflammation. It exerts its biological functions via interaction with its receptors, including receptor for advanced glycation end products (RAGE) and Toll-like receptor 4(TLR4). A large number of studies showed a close link between inflammation and thrombosis. This review demonstrated the increased expression of HMGB-1 in thrombosis-related diseases, including coronary artery disease, stroke, peripheral arterial disease, disseminated intravascular coagulation, and venous thrombosis. Besides, it summarized the current understanding of the emerging link between HMGB-1 and thrombosis from three aspects: platelet, NETs, and coagulation and fibrinolysis factors. Finally, it explored the possible therapeutic strategies targeting HMGB-1 for treating thrombosis-related diseases.

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Section: Figsupporting

confidence: 74%

Emerging Role of High Mobility Group Box-1 in Thrombosis-Related Diseases

Pei

et al. 2018

Cell Physiol Biochem

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“…Recent years, several potential biomarkers were found to identify PAD in diabetic patients. For instance, serum high mobility group box 1 (HMGB1), broblast growth factor (FGF) 23 and osteopontin (OPN) have been correlated with the presence of PAD in diabetic patients [24,25]. In addition, thrombospondin-4 (TSP-4) levels were signi cantly increased with PAD severity in patients with concomitant diabetes and could be a novel marker of atherosclerotic activity [26].…”

Section: Discussionmentioning

confidence: 99%

Association of serum Cyr61 levels with peripheral arterial disease in patients with type 2 diabetes

Feng

Sun

et al. 2020

Preprint

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Background: The prevalence of peripheral artery disease (PAD) is obviously increased in diabetic patients. Existing evidences show that cysteine-rich angiogenic inducer 61 (Cyr61), a 40 kD secreted protein, plays important roles in regulating cellular physiological processes. Recent studies have demonstrated a significant correlation between serum Cyr61 levels and atherosclerosis. However, the relationship between Cyr61 levels and PAD in type 2 diabetic patients remains obscure.Methods:. A total of 306 subjects with type 2 diabetes were recruited. The extent of PAD was determined by using the Fontaine classification, which defines four stages. We analyzed Cyr61 serum levels by ELISA in patients with and without PAD at Fontaine’s stage II, III, or IV. Logistic regression models were used to examine the independent association of Cyr61 with PAD.Results: Out of the 306 patients enrolled in this study, 150 patients were free from PAD, while 156 had clinically significant PAD. In PAD patients, the prevalences of Fontaine classification stage II, III and IV were 48.7%, 32.1%, and 19.2%, respectively. Patients with more advanced PAD had significantly higher Cyr61 (P for trend <0.001). The prevalence of PAD on the basis of severity increased with ascending Cyr61 quartiles (all P for trend <0.001), and the severity of PAD was positively correlated with Cyr61 quartiles (r=0.227, P=0.006). The association of Cyr61 levels with PAD remained after adjusting for major risk factors in a logistic regression analysis.Conclusions: Our results demonstrated that Cyr61 was significantly increased in type 2 diabetic patients with PAD and that Cyr61 levels were positively associated with disease severity. It could be a promising biomarker and further studies are needed to assess its clinical utility.

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“…Despite similar baseline clinical characteristics-in terms of risk factor control and PAD severity-and the same endovascular approach, some patients do not encounter complications for years while other patients may have complications, even fatal, within a few months [26]. Several potential biomarkers have been proposed, some linked to patient's genetic characteristics [25,[27][28][29], many linked metabolic and in ammatory parameters [19,25,[30][31][32][33]. Among the possible candidates, the pathways linked to adipose tissue represent a promising eld of study.…”

Section: Discussionmentioning

confidence: 99%

Association between Omentin-1 and Major Cardiovascular Events After Lower Extremity Endovascular Revascularization in Diabetic Patients: A Prospective Cohort Study

Biscetti

Nardella

Rando

et al. 2020

Preprint

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Background: Cardiovascular complications represent the major cause of morbidity and mortality of type 2 diabetes mellitus (T2DM) patients. In particular, peripheral artery disease (PAD) represents a frequent T2DM vascular complication and a risk factor for the development of major adverse cardiovascular events (MACE). Among adipokines, Omentin-1 serum levels are reduced in T2DM patients with PAD and are inversely related to disease severity.Objective: To study the relationship between Omentin-1 levels, at baseline, with outcomes after endovascular procedures in T2DM patients with PAD and chronic limb-threatening ischemia (CLTI).Research Design and Methods: We enrolled for our prospective non-randomized study, 207 T2DM patients with PAD and CLTI, requiring revascularization. Omentin-1 serum levels were collected before revascularization and patients incidence outcomes were evaluated at 1, 3, 6 and 12 months.Results: Omentin-1 was reduced in patients with more severe disease (27.24 ± 4.83 ng/mL vs 30.82 ± 5.48 ng/mL, p < 0.001). Overall, 84 MACE and 96 major adverse limb events (MALE) occurred during the 12-month follow-up. We observed that Omentin-1 levels were lower in patients with MACE (26.02 ± 4.05 ng/mL vs 31.33 ± 5.29 ng/mL, p < 0.001) and MALE (26.67 ± 4.21 ng/mL vs 31.34 ± 5.54 ng/mL, p < 0.001). The association between Omentin-1, MACE and MALE remained significant after adjusting for major risk factors in a multivariate analysis. Receiver operating characteristics (ROC) curve using Omentin-1 levels predicted incidence events (area under the curve = 0.80).Conclusions: We demonstrated that reduced Omentin-1 levels, at baseline, are related with worse vascular outcomes in T2DM patients with PAD and CLTI undergoing an endovascular procedure.

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Serum high mobility group box-1 and osteoprotegerin levels are associated with peripheral arterial disease and critical limb ischemia in type 2 diabetic subjects

Cited by 59 publications

References 54 publications

Emerging Role of High Mobility Group Box-1 in Thrombosis-Related Diseases

Emerging Role of High Mobility Group Box-1 in Thrombosis-Related Diseases

Association of serum Cyr61 levels with peripheral arterial disease in patients with type 2 diabetes

Association between Omentin-1 and Major Cardiovascular Events After Lower Extremity Endovascular Revascularization in Diabetic Patients: A Prospective Cohort Study

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