Bidimentional in vitro angiogenic assays to study CCM pathogenesis: Endothelial cell proliferation and migration

Abstract

Cerebral cavernous malformation (CCM) is a cerebrovascular disorder of proven genetic origin characterized by abnormally dilated and leaky capillaries occurring mainly in the central nervous system, with a prevalence of 0.3–0.5% in the general population. Genetic studies have identified three genes associated to CCMs: KRIT1 (CCM1), MGC4607 (CCM2), and PDCD10 (CCM3), which account for about 50%, 20%, and 10% of the cases, respectively. The great advances in the knowledge of the physiopathological functions of CCM genes, such as their involvement in the angiogenic process, have allowed to propose distinct putative therapeutic compounds, which showed to be effective at least in limiting some pathological phenotypes in cellular and animal models of the disease. However, despite numerous efforts, targeted pharmacological therapies that improve the outcome of CCM disease are currently lacking. Here we describe simply and low-cost assays as in vitro endothelial cell proliferation and migration assays that can be used to better understand the role of CCM genes on endothelial cell functions and to screen potential new compounds for CCM therapy.