High Mobility Group Box-1: A Missing Link between Diabetes and Its Complications

Table 1

Functions of HMGB-1 in diabetic cardiovascular complications.

Diseases/pathological phenomena	Involved signal molecule(s)	Notes	Ref.
CAD	HMGB-1	Elevated serum levels in diabetic patients with CAD.	[21]
CAD	HMGB-1	Serum HMGB-1 was increased in CAD patients with T2DM.	[41]
AMI	HMGB-1	HMGB-1 expression in thrombus was higher in AMI patients with DM and was positively correlated with blood glucose.	[42]
DCM	HMGB-1	Increased HMGB-1 expression in myocardial tissue of DCM.	[43]
DCM	HMGB-1, TGF-1beta, collagens, MMP2, MMP9, ERK, JNK, Akt	HMGB-1 promoted myocardial fibrosis and dysfunction in DCM.; HMGB-1 mediated HG-induced TGF-1beta, collagens, and MMPs expressions in cardiac cells.; Involvement of HMGB-1 in HG-induced cardiac fibroblasts proliferation and migration.	[44]
DCM	HMGB-1, RAGE	HMGB-1/RAGE may be involved in HG-induced cardiomyocytes injury.	[45]
Foot atherogenesis	HMGB-1, VCAM, NF-κB	HMGB-1-induced inflammation mediated pathogenesis of diabetic foot atherogenesis.	[46]
I/R injury	HMGB-1, RAGE, NF-κB, TNF-α, IL-6	HG induced inflammatory response via HMGB-1/RAGE/NF-κB pathway in I/R models.	[47]
Endothelial dysfunction	HMGB-1, ROS	HMGB-1 mediated ROS genesis in AGEs-induced EPCs.	[27]
Endothelial dysfunction	Oxidative stress, HMGB-1, RAGE, ERK, NF-κB	HMGB-1 induced endothelial dysfunction via oxidative stress and RAGE/ERK/NF-κB pathway.	[34]
Endothelial dysfunction	HMGB-1, RAGE, MMP9	Serum HMGB-1 may reflect endothelial dysfunction developing in DM.	[22]
Cardiomyocyte apoptosis	HMGB-1, ERK, Ets-1, caspase-3, Bax/Bcl-2	HMGB-1 mediated hyperglycaemia-induced cardiomyocyte apoptosis.	[28]

CAD: coronary artery disease; T2DM: type 2 diabetes mellitus; AMI: acute myocardial infarction; DM: diabetes mellitus; DCM: diabetic cardiomyopathy; TGF-1beta: transforming growth factor-1beta; MMP2: matrix metalloproteinase-2; MMP9: matrix metalloproteinase-9; ERK: extracellular signal-regulated kinase; JNK: c-Jun N-terminal kinase; HG: high glucose; RAGE: receptor for advanced glycation end product; VCAM: vascular cell adhesion molecule; NF-κB: nuclear factor-κB; I/R: ischemia-reperfusion; TNF-α: tumor necrosis factor-α; IL-6: interleukin-6; EPC: endothelial progenitor cell; ROS: reactive oxygen species; AGEs: advanced glycation end products; HUVEC: human umbilical vein endothelial cell; Bax/Bcl-2: ratio of Bcl-2-associated X protein to B-cell lymphoma/leukemia-2; Ets-1: E26 transformation-specific sequence-1; Ref.: references.