Biologically Active Lipids in Vascular Biology

Biologically active lipids play numerous important roles in controlling vascular functions both in physiological and pathological settings. While enzymatically formed bioactive lipids mainly control physiological reactions involved in constriction and relaxation, as well as in providing an anticoagulant vessel surface, nonenzymatic lipid oxidation products have largely been implicated in controlling and driving a variety of blood vessel pathologies. Bioactive lipids are sensed by all cell types in the vascular wall. A variety of lipids control pro- and anti-inflammatory responses, endothelial barrier function, migration and phenotypic switching in smooth muscle cells, and macrophage phenotypic polarization and function. The biological effects of enzymatically formed bioactive lipids are mainly mediated via G protein-coupled receptors. Depending on specific receptor recognition, S1P and oxysterols can elicit either pro-inflammatory or anti-inflammatory effects. On the other hand, lipid oxidation products are recognized by two classes of less specific receptors called pattern recognition receptors and scavenger receptors. They may also directly modify proteins and enzymes thereby affecting a variety of vascular functions and contribute to inflammatory responses of the vessel wall, sometimes involving activation of inflammasomes. Oxidized lipids present in oxidized lipoproteins (oxLDL) enhance the formation of foam cells (i.e., lipid-laden macrophages). These oxidized lipids induce a specific stress response in macrophages that involves Nrf2-dependent upregulation of antioxidant and detoxifying enzymes.