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(Circulation Research. 2009;104:1217.)
© 2009 American Heart Association, Inc.

Integrative Physiology

Reduced Vessel Elasticity Alters Cardiovascular Structure and Function in Newborn Mice

Jessica E. Wagenseil, Chris H. Ciliberto, Russell H. Knutsen, Marilyn A. Levy, Attila Kovacs, Robert P. Mecham

From the Departments of Cell Biology and Physiology (J.E.W., C.H.C., R.H.K., M.A.L., R.P.M.) and Internal Medicine, Cardiovascular Division (A.K.), Washington University School of Medicine, St Louis, Mo.

Correspondence to Jessica E. Wagenseil, Department of Biomedical Engineering, Saint Louis University, 3507 Lindell Blvd, St Louis, MO 63103. E-mail jwagense{at}slu.edu

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.

Key Words: blood pressure • cardiovascular physiology • development • extracellular matrix • large artery stiffness

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