Related Experiment Video
Updated: May 3, 2026
Assessing Therapeutic Angiogenesis in a Murine Model of Hindlimb Ischemia
Published on: June 8, 2019
Circulating HMGB2 Is Associated With Angiographic Coronary Collateralization in Diabetic Patients With Chronic Total
Zhi Ming Wu1, Shuai Chen1, Yang Dai2
1Department of Cardiovascular Medicine, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine.
Insights
High mobility group box 2 (HMGB2) is linked to poor coronary collateralization in diabetic patients with coronary chronic total occlusion (CTO). HMGB2 also impairs blood vessel growth and is mediated by NLRP3.
Area of Science:
- Cardiovascular Biology
- Diabetology
- Immunology
Background:
- High mobility group box 2 (HMGB2) is associated with cardiovascular diseases.
- The role of HMGB2 in coronary collateralization remains unclear.
Purpose of the Study:
- To investigate the association between serum HMGB2 levels and coronary collateralization in patients with type 2 diabetes and coronary chronic total occlusion (CTO).
- To explore the mechanism by which HMGB2 affects angiogenesis and collateral vessel formation in a diabetic context.
Main Methods:
- Serum HMGB2 levels were measured in 322 diabetic CTO patients and correlated with coronary collateral status (Rentrop classification).
- The effect of anti-HMGB2 antibody was assessed in a diabetic mouse hindlimb ischemia model.
- Human umbilical vein endothelial cells (HUVECs) were used to study HMGB2's impact on angiogenesis and pyroptosis.
Main Results:
- Serum HMGB2 levels were significantly higher in patients with poor coronary collaterals (Rentrop score 0-1) compared to those with good collaterals (Rentrop score 2-3).
- HMGB2 was identified as an independent predictor of poor coronary collateralization.
- Anti-HMGB2 antibody administration improved blood flow restoration in diabetic mice with hindlimb ischemia.
- HMGB2 inhibited HUVEC migration and tube formation and promoted NLRP3-mediated pyroptosis under high-glucose and hypoxic conditions.
Conclusions:
- Elevated HMGB2 is associated with poor coronary collateralization in diabetic CTO patients.
- HMGB2 negatively impacts angiogenesis and collateral vessel development in diabetes, partly through NLRP3 activation.
Background:
HMGB2 is reported to be strongly associated with cardiovascular diseases, but its relationship with coronary collateralization is unclear.
Methods And Results:
We determined the serum HMGB2 levels in 322 patients with type 2 diabetes and coronary chronic total occlusion (CTO), and evaluated the degree of coronary collaterals by Rentrop classification (poor collaterals: Rentrop score 0 or 1; good collaterals: Rentrop score 2 or 3). Anti-HMGB2 neutralizing antibody was administered in a diabetic ischemic hindlimb mouse model, followed by laser Doppler perfusion imaging and histological examinations. Human umbilical vein endothelial cells (HUVECs) were treated with HMGB2 to assess the potential mechanisms. Serum HMGB2 decreased stepwise across Rentrop score 0 to 3 (P<0.001), with significantly higher levels in patients with poor collaterals than in those with good collaterals (P<0.001). After adjustment for various confounders, HMGB2 remained an independent factor for poor coronary collateralization (adjusted odds ratio, 1.234; 95% confidence interval, 1.136-1.340; P<0.001). In diabetic mice with hindlimb ischemia, administration of anti-HMGB2 neutralizing antibody increased blood flow restoration. HMGB2 inhibited migration and tube formation of HUVECs in a dose-dependent manner under high-glucose and hypoxic conditions, and promoted NLRP3-mediated pyroptosis.
Conclusions:
Elevated circulating HMGB2 was associated with poor coronary collateralization in CTO patients with diabetes. HMGB2 impaired angiogenesis and collateral vessel growth in diabetic mice. Such effects are mediated by NLRP3.
Related Concept Videos
01:30Peripheral Artery Disease I: Introduction
01:28Diabetic Nephropathy
01:22Diabetic Neuropathy