The importance of elastin to aortic development in mice.
Elastin is an essential component of vertebrate arteries that provides elasticity and stores energy during the cardiac cycle. Elastin production in the arterial wall begins midgestation but increases rapidly during the last third of human and mouse development, just as blood pressure and cardiac output increase sharply. The aim of this study is to characterize the structure, hemodynamics, and mechanics of developing arteries with reduced elastin levels and determine the critical time period where elastin is required in the vertebrate cardiovascular system. Mice that lack elastin (Eln(-/-)) or have approximately one-half the normal level (Eln(+/-)) show relatively normal cardiovascular development up to embryonic day (E) 18 as assessed by arterial morphology, left ventricular blood pressure, and cardiac function. Previous work showed that just a few days later, at birth, Eln(-/-) mice die with high blood pressure and tortuous, stenotic arteries. During this period from E18 to birth, Eln(+/-) mice add extra layers of smooth muscle cells to the vessel wall and have a mean blood pressure 25% higher than wild-type animals. These findings demonstrate that elastin is only necessary for normal cardiovascular structure and function in mice starting in the last few days of fetal development. The large increases in blood pressure during this period may push hemodynamic forces over a critical threshold where elastin becomes required for cardiovascular function. Understanding the interplay between elastin amounts and hemodynamic forces in developing vessels will help design treatments for human elastinopathies and optimize protocols for tissue engineering.
Wagenseil
Jessica E
JE
Dept. of Biomedical Engineering, Saint Louis Univ., 3507 Lindell Blvd., St. Louis, MO 63103, USA. jwagense@slu.edu
Ciliberto
Christopher H
CH
Knutsen
Russell H
RH
Levy
Marilyn A
MA
Kovacs
Attila
A
Mecham
Robert P
RP
D000818:Animals; D001011:Aorta / Q000196:embryology / Q000254:growth & development / Q000378:metabolism* / Q000503:physiopathology / Q000648:ultrastructure; D001794:Blood Pressure; D003187:Compliance; D003251:Constriction, Pathologic; D015150:Echocardiography, Doppler; D004549:Elastin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006439:Hemodynamics; D040542:Mechanotransduction, Cellular; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009131:Muscle, Smooth, Vascular / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D038081:Organogenesis; D012039:Regional Blood Flow; D013314:Stress, Mechanical; D016277:Ventricular Function, Left; D017725:Ventricular Pressure
D004549:Elastin