Regulation of Cell Signaling and Function by Endothelial Caveolins: Implications in Disease

Caveolae are cholesterol- and glycosphingolipid-rich omega-shaped invaginations of the plasma membrane that are very abundant in vascular endothelial cells and present in most cell types. Caveolins are the major coat protein components of caveolae. Multiple studies using knockout mouse, small interfering RNA, and cell-permeable peptide delivery approaches have significantly enhanced our understanding of the role of endothelial caveolae and caveolin-1 in physiology and disease. Several postnatal pulmonary and cardiovascular pathologies have been reported in caveolin-1 knockout mice, many of which have been recently rescued by selective re-expression of caveolin-1 in endothelium of these mice. A large body of experimental evidence mostly using caveolin-1 knockout mice suggests that, depending on the disease model, endothelial caveolin-1 may play either a protective or a detrimental role. For instance, physiological or higher expression levels of caveolin-1 in endothelium might be beneficial in such diseases as pulmonary hypertension, cardiac hypertrophy, or ischemic injury. On the other hand, endothelial caveolin-1 might contribute to acute lung injury and inflammation, atherosclerosis or pathological angiogenesis associated with inflammatory bowel disease. Moreover, depending on the specific model, endothelial caveolin-1 may either promote or suppress tumor-induced angiogenesis. In addition to overwhelming evidence for the role of endothelial caveolin-1, more recent studies also suggest that endothelial caveolin-2 could possibly play a role in pulmonary disease. The purpose of this review is to focus on how caveolin-1 expressed in endothelial cells regulates endothelial cell signaling and function. The review places particular emphasis on relevance to disease, including but not limited to Pulmonary and cardiovascular disorders as well as cancer. In addition to caveolin-1, possible importance of the less-studied endothelial caveolin-2 in pulmonary diseases will be also discussed.