Cholesterol-mediated regulation of angiogenesis: An emerging paradigm

Angiogenesis, the fundamental process that generates new blood vessels from parental vessels, is essential for embryogenesis and pathogenesis. A variety of underlying molecular and cellular mechanisms control angiogenesis. In this review, we focus on a unique mechanism of action - cholesterol-regulated angiogenesis. We will discuss lipoproteins, including low-density lipoprotein and high-density lipoprotein, cholesterol-rich lipid rafts/caveolae, apoA-I-binding protein (AIBP, also known as NAXE)-regulated cholesterol efflux, the effect of the hydroxycholesterol-activated nuclear receptor liver X receptor α/β on the proangiogenic vascular endothelial growth factor receptor 2 and antiangiogenic Notch signaling, and cholesterol-modified sonic hedgehog signaling. These pathways can be exploited, either alone or in conjunction with the currently available regimen for angiogenesis treatment, to control neovascularization in dyslipidemia. A treatment protocol for angiogenesis that takes into consideration cholesterol management might constitute an important component in precision and personalized medicine.