Role of HMGB1 in cardiovascular diseases.
A nuclear protein, high mobility group box 1 (HMGB1), is released passively by necrotic cells, and actively by macrophages/monocytes in response to exogenous and endogenous inflammatory stimuli. After binding to the receptor for advanced glycation end products (RAGE) or toll-like receptor 4 (TLR4), HMGB1 activates vascular endothelial cells and macrophages/monocytes to express proinflammatory cytokines, chemokines and adhesion molecules. Pharmacological suppression of its activities or release is protective against lethal endotoxemia and sepsis, establishing HMGB1 as a critical mediator of lethal systemic inflammation. In light of the pathogenic role of inflammation in cardiovascular diseases, we propose that HMGB1, a proinflammatory cytokine derived from both injured endothelium and activated macrophages/monocytes, could contribute to the progression of atherosclerosis and other cardiovascular diseases.
Department of Emergency Medicine, North Shore University Hospital, New York University School of Medicine, 350 Community Drive, Manhasset, NY 11030, USA.
Wei
W
Li
Andrew E
AE
Sama
Haichao
H
Wang
D000595:Amino Acid Sequence; D002318:Cardiovascular Diseases / Q000209:etiology*; D024243:HMGB1 Protein / Q000009:adverse effects / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D008969:Molecular Sequence Data; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism
D024243:HMGB1 Protein; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic