Table 2.

HMGB1, diabetes mellitus and peripheral arterial disease, summary of the evidences. STZ: streptozotocin; VEGF: vascular endothelial growth factor; T2DM: type 2 diabetes mellitus; PAD: peripheral arterial disease; OPG: osteoprotegerin; TNF-α: Tumor Necrosis Factor-α; IL-6: interleukin 6; CRP: C-reactive protein; HASCs: human adipose-derived stem cells; DFU: diabetic foot ulceration.

Ref.	Year	Aim	HMGB1
Biscetti et al.	2010	Role of HMGB1 in diabetic angiogenesis.	Lower HMGB1 protein expression in the ischemic tissue of STZ-induced mice. HMGB1 administration ameliorates the blood flow recovery and capillary density in the ischemic muscle of STZ-induced mice. Reduced HMGB1-induced angiogenesis by inhibiting VEGF activity.
Tsao et al.	2015	Expression of HMGB1 in diabetic foot atherogenesis.	Increased HMGB1 expression in vessels of T2DM patients and T2DM patients with PAD compared to non-T2DM patients.
Giovannini et al.	2017	Role of HMGB1, OPG, TNF-α, IL-6, CRP in diabetic patients with PAD.	Increased serum levels of HMGB1 in T2DM patients with PAD. Levels of HMGB1 positively correlates with severity of PAD in T2DM patients. HMGB1 independent risk factor for PAD in T2DM patients.
Biscetti et al.	2017	Role of HMGB1 in cell therapy with HASCs in PAD.	Improved blood flow recovery in mice co-treated with HASCs and HMGB1 protein, compared to HASCs-treated mice. Reduced post-ischemic angiogenesis with HMGB1 inhibition in mice co-treated with HASCs and HMGB1.
Hafez et al.	2018	Role of Sirtuin-1 and HMGB1 in DFU.	Increased serum levels HMGB1 and AGEs in T2DM patients compared to non-T2DM patients with the highest levels in T2DM patients with DFU.