How much is too much? Interleukin-6 and its signalling in atherosclerosis.
The importance of inflammation as a driver of pathology is no longer confined to autoimmune and infectious diseases. In line with convincing experimental data as well as abundant clinical findings the current view of atherosclerosis points to inflammation as a critical regulator of atherosclerotic plaque formation and progression leading to the fatal clinical endpoints myocardial infarction, stroke or sudden cardiac death. The underlying mechanisms have been a matter of intense research during the last decades. In this regard, the interleukin-6 (IL-6) cytokines and their signalling events have been shown to contribute to both, atherosclerotic plaque development and plaque destabilisation via a variety of mechanisms. These involve the release of other pro-inflammatory cytokines, oxidation of lipoproteins by phospholipases, stimulation of acute phase protein secretion, the release of prothrombotic mediators, and the activation of matrix metalloproteinases. Moreover, the formation of reactive oxygen species generated by vascular enzyme systems may play a critical role in the regulation of IL-6 indicating a cross talk between vasoactive substances i.e. angiotensin II or adrenalin and pro-inflammatory cytokines such as IL-6. In this review we will summarise and discuss the underlying molecular and cellular mechanisms how IL-6 as an early and central regulator of inflammation contributes to atherosclerosis and how this knowledge can be integrated into the clinical context.
Schuett
Harald
H
Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg Strasse 1, 30165 Hannover, Germany.
Luchtefeld
Maren
M
Grothusen
Christina
C
Grote
Karsten
K
Schieffer
Bernhard
B
D000210:Acute-Phase Reaction / Q000503:physiopathology; D000818:Animals; D050197:Atherosclerosis / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy; D050822:Cytokine Receptor gp130 / Q000502:physiology; D004195:Disease Models, Animal; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology*; D051379:Mice; D008955:Models, Cardiovascular; D012084:Renin-Angiotensin System / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
C508600:IL6 protein, human; D015850:Interleukin-6; D050822:Cytokine Receptor gp130