Reduced vessel elasticity alters cardiovascular structure and function in newborn mice.
Elastic blood vessels provide capacitance and pulse-wave dampening, which are critically important in a pulsatile circulatory system. By studying newborn mice with reduced (Eln(+/)(-)) or no (Eln(-)(/)(-)) elastin, we determined the effects of altered vessel elasticity on cardiovascular development and function. Eln(-)(/)(-) mice die within 72 hours of birth but are viable throughout fetal development when dramatic cardiovascular structural and hemodynamic changes occur. Thus, newborn Eln(-)(/)(-) mice provide unique insight into how a closed circulatory system develops when the arteries cannot provide the elastic recoil required for normal heart function. Compared with wild type, the Eln(-)(/)(-) aorta has a smaller unloaded diameter and thicker wall because of smooth muscle cell overproliferation and has greatly reduced compliance. Arteries in Eln(-)(/)(-) mice are also tortuous with stenoses and dilations. Left ventricular pressure is 2-fold higher than wild type, and heart function is impaired. Newborn Eln(+/)(-) mice, in contrast, have normal heart function despite left ventricular pressures 25% higher than wild type. The major vessels have smaller unloaded diameters and longer lengths. The Eln(+/)(-) aorta has additional smooth muscle cell layers that appear in the adventitia at or just before birth. These results show that the major adaptive changes in cardiovascular hemodynamics and in vessel wall structure seen in the adult Eln(+/)(-) mouse are defined in late fetal development. Together, these results show that reduced elastin in mice leads to adaptive remodeling, whereas the complete lack of elastin leads to pathological remodeling and death.
Department of Cell Biology, Washington University School of Medicine, St Louis, MO, USA. jwagense@slu.edu
Jessica E
JE
Wagenseil
Chris H
CH
Ciliberto
Russell H
RH
Knutsen
Marilyn A
MA
Levy
Attila
A
Kovacs
Robert P
RP
Mecham
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001011:Aorta / Q000166:cytology / Q000502:physiology*; D001158:Arteries / Q000166:cytology / Q000502:physiology*; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000033:anatomy & histology* / Q000166:cytology / Q000378:metabolism; D049109:Cell Proliferation; D004548:Elasticity / Q000502:physiology*; D004549:Elastin / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000033:anatomy & histology / Q000166:cytology / Q000378:metabolism; D014664:Vasodilation / Q000502:physiology; D016277:Ventricular Function, Left / Q000502:physiology
D004549:Elastin