Plvap/PV1 critical to formation of the diaphragms in endothelial cells

January 3, 2013

Dartmouth scientists have demonstrated the importance of the gene Plvap and the structures it forms in mammalian physiology in a study published in December by the journal Developmental Cell.

"The knowledge generated and the animal models created will allow a better understanding of the role of the gene in diseases and will help validate its usefulness as a therapeutic or diagnostic ," said lead author Radu V. Stan, MD, associate professor, Geisel School of Medicine at Dartmouth, and member of the Dartmouth-Hitchcock Norris Cotton Cancer Center (NCCC).

The study demonstrates that plasmalemma vesicle associated protein (PV1), a vertebrate gene specifically expressed in the vascular endothelial cells, is critical for the formation of the diaphragms of endothelial caveolae, fenestrae and transendothelial channels. Although discovered in the 1960s by , the function of the diaphragms was previously unknown. Using mice with loss and gain of PV1 function Dartmouth scientists demonstrated that the diaphragms of fenestrae are critical for maintenance of basal permeability, the homeostasis of in terms of protein and lipid blood composition, and ultimately survival.

PV1 has newly discovered roles in cancer and in various infectious and . "The knowledge generated and the animal models created will allow a better understanding of the role of the gene in these diseases and to validate its usefulness as a therapeutic or diagnostic target," said Stan.

In the absence of such diaphragms, extravasation produces a noninflammatory protein-losing enteropathy resulting in protein calorie malnutrition and ultimately death.

"Our results and the mouse models we have created provide the foundations for evaluating numerous aspects of basal permeability in fenestrated vascular beds," said Stan.

Explore further: New molecular pathway regulating angiogenesis may fight retinal disease, cancers

Related Stories

Enzyme offers new therapeutic target for cancer drugs

June 21, 2012

Researchers at the University of California, San Diego School of Medicine have uncovered a new signal transduction pathway specifically devoted to the regulation of alternative RNA splicing, a process that allows a single ...

Recommended for you

Combination therapy can prevent cytostatic resistance

November 26, 2015

Researchers at Karolinska Institutet have found a new way of preventing resistance to cytostatics used in the treatment of cancers such as medulloblastoma, the most common form of malignant brain tumour in children. The promising ...

Forecasting the path of breast cancer in a patient

November 23, 2015

USC researchers have developed a mathematical model to forecast metastatic breast cancer survival rates using techniques usually reserved for weather prediction, financial forecasting and surfing the Web.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.