Vascular permeability in cardiovascular disease and cancer.
OBJECTIVE
Regulation of endothelial barrier function is critical for vascular homeostasis, as dynamic and local control of vascular permeability permits macromolecular transport, immune surveillance, and deposition of a fibrin barrier to contain infection at sites of inflammation. Many of the signaling pathways promoting useful vascular permeability, however, are also triggered during disease, resulting in prolonged or uncontrolled vascular leak. Hyperpermeability triggered by inflammation or ischemia in the heart, brain, or lung promotes edema, exacerbates disease progression, and impairs recovery. During cancer, solid tumors release factors that promote the growth of leaky blood vessels which contribute to metastatic spread and limit targeted delivery of anticancer agents.


RESULTS
Although the molecular mechanisms governing vascular leak have been studied intensely over the last few decades, recent advances have identified new therapeutic targets that have begun to show preclinical and clinical promise. These approaches have been recently applied with success to an increasing number of disease models.


CONCLUSIONS
Designing new therapies to limit vascular leak during the progression of disease requires a more complete understanding of the molecular mechanisms governing the endothelial barrier function. This knowledge will benefit the treatment of a growing number of diseases from cardiovascular disease to cancer.
Weis
Sara M
SM
Moores UCSD Cancer Center, University of California, San Diego, California 92093-0803, USA. sweis@ucsd.edu
D000818:Animals; D002199:Capillary Permeability / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D042783:Endothelial Cells / Q000502:physiology; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000503:physiopathology*; D019108:Tight Junctions / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000502:physiology
D020741:rho GTP-Binding Proteins