AUGUSTA, Ga. - A protein known to promote cancer appears to give the blood vessels strength and shape, researchers report. When yes-associated protein, or YAP, is deleted from vascular smooth muscle cells during development, the protein makes thin-walled blood vessels that over-dilate in response to the usual pressure of blood flow, said Dr. Jiliang Zhou, vascular biologist at the Medical College of Georgia at Georgia Regents University.
"The thickness of the arterial wall decreases from three or four layers of smooth muscle cells to one or two layers," said Zhou, corresponding author of the study featured on the cover of the American Heart Association journal, Circulation Research.
The researchers also found that YAP appears to manage vascular smooth muscle cells by controlling expression of the cell cycle arrest gene, Gpr132. During growth, YAP suppresses this suppressor then, when blood vessels walls are the right size, YAP expression decreases and Gpr132 expression increases.
"The balance shifts," Zhou said. When the scientists deleted YAP in mice, Gpr132 expression increased and cell proliferation decreased. Conversely, knocking down Gpr132 expression increases vascular smooth muscle cell proliferation.
The study required deleting YAP from both vascular smooth muscle cells and heart cells technology does not enable more selective removal so the mice also were born with significant heart defects, confirming the protein's key role in heart formation. YAP's absence has been shown to cause, for example, ventricular septal defects, a common congenital heart defect in which a persistent hole between the right and left ventricle can lead to heart failure.
The mice in this study died shortly after birth from significant heart and vascular defects. Zhou suspects that less severe alterations in YAP may also produce aneurysms, weak points in the vascular system that often go undetected before rupturing
|Contact: Toni Baker|
Medical College of Georgia at Georgia Regents University