The role of complement in the development and manifestation of murine atherogenic inflammation: novel avenues

Abstract

Atherosclerosis is a chronic progressive inflammatory disease which manifests in the arterial vascular tree. It is a major cause of cardiovascular morbidity and contributes significantly to mortality in the developed world. Triggers for this inflammatory process are elevated levels of cholesterol, bacterial infection and obesity. The immune response in atherosclerosis is essentially pro-atherogenic, leading to lipid accumulation and cellular changes within the arterial wall. Small-animal models of atherosclerosis are used to study the relevance of candidate factors (cells, genes, diets) in the development and progression of lesions. From a multidisciplinary viewpoint, there are challenges and limitations to this approach. Activation of complement determines or modifies the outcome of acute and chronic inflammation. This review dissects the role of complement in the early development as well as the progressive manifestation of murine atherosclerosis and the advances in knowledge provided by the use of specific mouse models. It gives a critical overview of existing models, analyses seemingly conflicting results obtained with complement-deficient mouse models, highlights the importance of interrelationships between pro-coagulpant activity, adipose tissue, macrophages and complement, and uncovers exciting avenues of topical research.