A Call for Rigorous Study of Statins in Resolution of Cerebral Cavernous Malformation Pathology

Cerebral cavernous malformations (CCMs) are cerebrovascular disorders with an approximate prevalence of 1 in 200. The CCM pathology is typified by abnormally dilated clusters of blood vessels with defective endothelial cell–cell junctions, sluggish blood flow, and almost always associated with hemosiderin deposition in the surrounding parenchyma.1–3 CCM can arise sporadically or be inherited in an autosomal dominant pattern.4–6 In some cases, CCMs cause hemorrhagic stroke that elicits neurological defects and rarely death. Extravasataion of blood components and hematoma expansion can often occur asymptomatically. Three structurally unrelated genes, CCM1 ( KRIT1 ), CCM2 ( MGC4607 ), and CCM3 ( PDCD10 ), have been implicated in CCM pathobiology.7–9 It is now thought that the CCM proteins form a ternary complex near the plasma membrane of endothelial cells and act as scaffolds linking the junctional proteins, integrins and vascular endothelial–cadherin, with intracellular signaling components.10 However, the specific mechanisms through which reductions in the expression of the structurally diverse genes associated with CCM induce their formation and pathobiology are not well explained. Studies using mouse and zebrafish models have been instrumental in functionally characterizing and, to an extent, faithfully recapitulating the molecular and ultrastructural underpinnings of CCM pathology. …