Roles of inflammation in the natural history of intracranial saccular aneurysms.

Aneurysmal subarachnoid hemorrhage is caused by intracranial aneurysm (IA) rupture and results in high rates of mortality and morbidity. Factors contributing to IA generation, growth and rupture can involve genetics, injury, hemodynamics, environmental factors, and inflammation, in which inflammatory factors are believed to play central roles in the whole natural history. Inflammatory reactions that contribute to IA development may involve synthesis of many functional proteins and expression of genes induced by changes of blood flow, external stimuli such as smoking, internal balance such as hormonal status changes, and blood pressure. Meanwhile, inflammatory reactions itself can evoke inflammatory cytokines release and aggregation such as MMPs, MCP-1, TNF-α and ZO-1, directly or indirectly promoting aneurysm growth and rupture. However, the details of these inflammatory reactions and their action on inflammatory chemokines are still unknown. Moreover, some agents with the function of anti-inflammation, lipid-lowering, antihypertension or inflammatory factor inhibition may have the potential benefit to reduce the risk of aneurysm development or rupture in a group of population despite the underlying mechanism remains unclear. Consequently, we reviewed the potential inflammatory responses and their mechanisms contributing to aneurysm development and rupture and sought intervention targets that may prevent IA rupture or generation. • Inflammatory factors have a tremendous impact on the overall development of IA. • ET-1- and ETBR can induce endothelial dysfunction before IA occurrence. • MMP-activated extracellular matrix degradation and macrophage- and TNF-α-mediated arterial wall inflammation lead to IA formation. • Anti-inflammation, lipid-lowering, antihypertension or inflammatory factor inhibition agents may have potential to reduce IA development or rupture. [ABSTRACT FROM AUTHOR]