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.
Li
Wei
W
Department of Emergency Medicine, North Shore University Hospital, New York University School of Medicine, 350 Community Drive, Manhasset, NY 11030, USA.
Sama
Andrew E
AE
Wang
Haichao
H
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