Smooth muscle cells and the formation, degeneration, and rupture of saccular intracranial aneurysm wall--a review of current pathophysiological knowledge.

Subarachnoid hemorrhage or intracerebral hemorrhage caused by rupture of a saccular intracranial aneurysm (sIA) is often fatal and causes significant loss of productive live years in addition to significant mortality. Around 3.5 % of the middle aged otherwise healthy population carries unruptured sIAs. Many sIAs never rupture, and since their prophylactic treatment is associated with risks of morbidity and even mortality, it is paramount to elucidate the biology that leads to sIA rupture in order be able to identify rupture-prone sIAs and to improve current therapies. Smooth muscle cells (SMCs) play a critical role both in the formation of sIAs, as well as in the repair and adaptation of the sIA wall to hemodynamic and proteolytic stress to which it is subjected. Loss of mural SMCs is characteristic to ruptured sIA walls, and experiments in animal models suggest that this loss of mural SMCs is causative to sIA growth and eventual rupture. Genetic factors that impair the function or survival of SMCs may predispose to sIA formation. Local or systemic therapy that increases the number of functioning SMCs in the sIA wall may have a potential to reduce the risk of sIA rupture. This review discusses the mechanisms and cellular interactions that SMCs have in the pathobiology of the sIA wall.