Multiple Functions and Clinical Uses of Caveolae in Endothelium

Caveolae were first identified half a century ago by electron microscopy (EM) as small, flask-shaped, smooth plasmalemmal invaginations. They are most abundant in certain endothelial cells (ECs) and adipocytes but exist in many other cell types. For the next 40 years, exploration into these mysterious organelles was limited primarily to morphological study by EM, including transendothelial transport studies using electron-dense tracers. Until recently, when caveolae were considered at all, they were thought at best to function only in fluid-phase endocytosis (the uptake of small molecules and/or fluids surrounding the cell, also known as pinocytosis ) and thus were frequently called pinocytic or “drinking” vesicles. During the last decade, the development of new molecular tools, markers, and purification techniques that permit selective functional and architectural analysis of caveolae has led to a renaissance in the research of caveolae and to new insights into their structure, composition, physiology, and function. This renewal has been fueled further by key fundamental discoveries of their role in important cellular processes, including signaling and mechanotransduction, cholesterol trafficking, cell growth, and membrane trafficking. Selective targeting of caveolae in vivo can mediate tissue-specific delivery of substances to the endothelium and even across the endothelial layer (via transcytosis) into underlying tissue. In this chapter, we discuss the structure, purification, and composition of caveolae, their relation to lipid rafts, and their role in trafficking and signaling, with emphasis on functions pertinent mostly to ECs, such as acute mechanotransduction and transcytosis. The possible clinical utility of caveolae in the vascular targeting of drugs, genes, and nanomedicines also is presented.