Association Between Carotid Plaque Vulnerability and High Mobility Group Box-1 Serum Levels in a Diabetic Population

Biscetti, Federico; Tinelli, Giovanni; Rando, Maria Margherita; Nardella, Elisabetta; Cecchini, Andrea Leonardo; Angelini, Flavia; Straface, Giuseppe; Filipponi, Marco; Arena, Vincenzo; Pitocco, Dario; Gasbarrini, Antonio; Massetti, Massimo; Flex, Andrea

doi:10.21203/rs.3.rs-362250/v1

Cited by 4 publications

(5 citation statements)

References 40 publications

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“…Furthermore, Wang and colleagues demonstrated that LPS/ATP activation of NLRP3 in ammasome stimulates HMGB-1 release leading to cholesterol accumulation in VSMCs and foam cells formation during atherosclerosis, through the downregulation of LXRa and ABCA1 expression (58). HMGB-1 is even responsible of atherosclerotic plaque vulnerability, possibly through VSMCs secretion of matrix metalloproteinase (MMP), enzymes responsible for matrix degradation (32,59).…”

Section: Discussionmentioning

confidence: 99%

“…Different evidences show a role of HMGB-1 in cardiovascular diseases development. It has been associated to coronary artery disease (28-31) and it represents an independent risk factor for carotid plaque vulnerability (32). In addition, we previous observed that levels of HMGB-1 were higher in patients with PAD and diabetes mellitus compared to those without diabetes mellitus (33).…”

Section: Introductionmentioning

confidence: 91%

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Serum high mobility group box-1 levels associated with cardiovascular events after lower extremity revascularization: a prospective study of a diabetic population

Rando

Biscetti

Cecchini

et al. 2022

Preprint

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Background: Peripheral arterial disease (PAD) is one of the most disabling cardiovascular complications of type 2 diabetes mellitus and is indeed associated with a high risk of cardiovascular and limb adverse events. High mobility group box-1 (HMGB-1) is a nuclear protein involved in the inflammatory response that acts as a pro-inflammatory cytokine when released into the extracellular space. HMBG-1 is associated with PAD in diabetic patients.The aim of this study was to evaluate the association between serum HMGB-1 levels and major adverse cardiovascular events (MACE) and major adverse limb events (MALE) after lower-extremity endovascular revascularization (LER) in a group of diabetic patients with chronic limb-threatening ischemia (CLTI).Methods: we conducted a prospective observational study of 201 diabetic patients with PAD and CLTI requiring LER. Baseline serum HMGB-1 levels were determined before endovascular procedure. Data on cardiovascular and limb outcomes were collected in a 12-month follow-up. Results: During the follow-up period, 81 cases of MACE and 93 cases of MALE occurred. Patients who subsequently developed MACE and MALE had higher serum HMGB-1 levels. Specifically, 7.5 ng/mL vs 4.9 ng/mL (p < 0.01) for MACE and 7.2 ng/mL vs 4.8 ng/mL (p < 0.01) for MALE. After adjusting for traditional cardiovascular risk factors, the association between serum HMGB-1 levels and cardiovascular outcomes remained significant in multivariate analysis. In our receiver operating characteristic (ROC) curve analysis, serum HMGB-1 levels were a good predictor of MACE incidence (area under the curve [AUC] = 0.78) and MALE incidence (AUC = 0.75).Conclusions: This study demonstrates that serum HMGB-1 levels are associated with the incidence of MACE and MALE after LER in diabetic populations with PAD and CLTI.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

Serum high mobility group box-1 levels associated with cardiovascular events after lower extremity revascularization: a prospective study of a diabetic population

Rando

Biscetti

Cecchini

et al. 2022

Preprint

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“…It has been postulated a compensatory, yet often failed, self-defence response of OPG to atherogenesis. On the other hand, OPG can exert pro-inflammatory effects; by increasing macrophage infiltration and leukocyte adhesion to endothelial cells, and sensitizing them to the effects of TNF-alpha via upregulation of angiopoietin-2 [33,34]. RANKL promotes osteogenic differentiation of vascular smooth muscle cell and stimulates the release of various pro-inflammatory cytokines, such as matrix metalloproteinase (MMP)-9, while TRAIL is a potent activator of apoptosis.…”

Section: Osteoprotegerin and Atherosclerotic Pathophysiological Mecha...mentioning

confidence: 99%

Association of serum levels of osteopontin and osteoprotegerin with adverse outcomes after endovascular revascularisation in peripheral artery disease

Kadoglou

Kapetanios

Korakas

et al. 2022

Cardiovasc Diabetol

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Background Osteoprotegerin (OPG) and osteopontin (OPN) are vascular calcification inhibitors with a known role in the atherosclerotic and inflammatory process. We investigated their relationship with adverse outcomes (restenosis/adverse cardiovascular events) after endovascular revascularisation of patients with peripheral arterial disease (PAD). Methods 203 consecutive patients were enrolled in the PAD group (PADG) and 78 age and sex-matched subjects with less than two cardiovascular risk factors served as control group (COG). PADG underwent standard medical assessment at baseline and 12 months after the procedure. During follow up major adverse cardiovascular events (MACEs) including arterial restenosis with need for reintervention were documented and the PADG was divided accordingly into two subgroups. Results During 12-month follow-up, 82 MACE were recorded (MACE subgroup). The rest of 124 PAD patients remained free of MACE (non-MACE subgroup). At baseline, OPG (9.89 ± 2.85 ng/ml vs 3.47 ± 1.95 ng/ml, p < 0.001) and OPN (79.99 ± 38.29 ng/ml vs 35.21 ± 14.84 ng/ml, p < 0.001) levels were significantly higher in PADG compared to COG, as well as in MACE subgroup compared to non-MACE subgroup (13.29 ± 3.23 ng/ml vs 10.86 ± 3 ng/ml and 96.45 ± 40.12 ng/ml vs 78.1 ± 38.29 ng/ml, respectively). An independent association of PAD with OPG and OPN was found in the whole patient cohort. Although OPG and OPN were significantly related to MACE incidence in the univariate analysis, multiple logistic regression analysis failed to detect any independent predictor of MACE within the PADG. Conclusion Baseline high OPG and OPN levels were independently associated with PAD presence. Even higher levels of those biomarkers were detected among PAD patients with MACE, however, their prognostic role should be further clarified.

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“…On the other hand, miR-21 can inhibit VSMC apoptosis by increasing the rate of proliferation of VSMCs in mouse carotid arteries and jointly protecting fibrous cap stability in atherosclerotic plaques [123]. It has been shown that hyperglycemia and streptozotocin-induced type 1 diabetes can reduce the synthesis of collagen and lead to the formation of unstable atherosclerotic plaques in ApoE -/mice [124]. Metformin can increase the level of activator protein 2 alpha (AP-2α) in carotid atherosclerotic plaques in diabetic ApoE -/mice, decrease the expression levels of miR-124, and increase the levels of prolyl-4-hydroxylase alpha 1 (P4Hα1) and collagen in VSMCs.…”

Section: Ncrnas In Vsmcsmentioning

confidence: 99%

Targeting non-coding RNAs in unstable atherosclerotic plaques: Mechanism, regulation, possibilities, and limitations

Yang

Wang

et al. 2021

Int. J. Biol. Sci.

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Cardiovascular diseases (CVDs) caused by arteriosclerosis are the leading cause of death and disability worldwide. In the late stages of atherosclerosis, the atherosclerotic plaque gradually expands in the blood vessels, resulting in vascular stenosis. When the unstable plaque ruptures and falls off, it blocks the vessel causing vascular thrombosis, leading to strokes, myocardial infarctions, and a series of other serious diseases that endanger people's lives. Therefore, regulating plaque stability is the main means used to address the high mortality associated with CVDs. The progression of the atherosclerotic plaque is a complex integration of vascular cell apoptosis, lipid metabolism disorders, inflammatory cell infiltration, vascular smooth muscle cell migration, and neovascular infiltration. More recently, emerging evidence has demonstrated that non-coding RNAs (ncRNAs) play a significant role in regulating the pathophysiological process of atherosclerotic plaque formation by affecting the biological functions of the vasculature and its associated cells. The purpose of this paper is to comprehensively review the regulatory mechanisms involved in the susceptibility of atherosclerotic plaque rupture, discuss the limitations of current approaches to treat plaque instability, and highlight the potential clinical value of ncRNAs as novel diagnostic biomarkers and potential therapeutic strategies to improve plaque stability and reduce the risk of major cardiovascular events.

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Association Between Carotid Plaque Vulnerability and High Mobility Group Box-1 Serum Levels in a Diabetic Population

Cited by 4 publications

References 40 publications

Serum high mobility group box-1 levels associated with cardiovascular events after lower extremity revascularization: a prospective study of a diabetic population

Serum high mobility group box-1 levels associated with cardiovascular events after lower extremity revascularization: a prospective study of a diabetic population

Association of serum levels of osteopontin and osteoprotegerin with adverse outcomes after endovascular revascularisation in peripheral artery disease

Targeting non-coding RNAs in unstable atherosclerotic plaques: Mechanism, regulation, possibilities, and limitations

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