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Review
. 2006 Apr;6(2):130-5.
doi: 10.1016/j.coph.2005.10.010. Epub 2006 Feb 17.

Role of HMGB1 in cardiovascular diseases

Wei Li  1 , Andrew E Sama, Haichao Wang
Affiliations
Review

Role of HMGB1 in cardiovascular diseases

Wei Li et al. Curr Opin Pharmacol. 2006 Apr.

Abstract

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.

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Figures

Figure 1
Figure 1
Amino acid sequence of human HMGB1. The C-terminal portion of HMGB1 contains an acidic (aspartic acid [D] and glutamic acid [E]) tail, and the N-terminal portion of HMGB1 comprises two internal repeats of a positively charged domain of about 80 amino acids (termed ‘HMG boxes’) (shown by bold text). The cytokine-stimulating motif (‘Cytokine domain’, shown by underline) of HMGB1 does not overlap with its RAGE-binding site (shown by underline), implicating the potential involvement of other cell surface receptors for HMGB1-mediated inflammatory responses.
Figure 2
Figure 2
Hypothetical roles of HMGB1 in the pathogenesis of atherosclosis. Atherosclerosis is characterized by focal thickenings of the innermost layer of the artery, the intima, which contains vascular endothelial, inflammatory (e.g. macrophages) and smooth muscle cells. It begins with an injury to the endothelial wall of the artery, and is followed by macrophage infiltration, and fatty streak accumulation. The uncontrolled growth of intima can subsequently lead to thrombus formation, followed by ischemic injury and myocardial infarction. In response to primary endothelial cell injury, HMGB1 may be passively released, which initiates a pronounced inflammatory response driven by endothelial cells as well as infiltrated innate immune cells. The injury-elicited inflammatory response could contribute to the pathogenesis of cardiovascular diseases. The pink area denotes the extracellular levels of HMGB1.
See this image and copyright information in PMC

References

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