Captopril treatment during development alleviates mechanically induced aortic remodeling in newborn elastin knockout mice.
Deposition of elastin and collagen in the aorta correlates with increases in blood pressure and flow during development, suggesting that the aorta adjusts its mechanical properties in response to hemodynamic stresses. Elastin knockout (Eln-/-) mice have high blood pressure and pathological remodeling of the aorta and die soon after birth. We hypothesized that decreasing blood pressure in Eln-/- mice during development may reduce hemodynamic stresses and alleviate pathological remodeling of the aorta. We treated Eln+/+ and Eln-/- mice with the anti-hypertensive medication captopril throughout embryonic development and then evaluated left ventricular (LV) pressure and aortic remodeling at birth. We found that captopril treatment decreased Eln-/- LV pressure to values near Eln+/+ mice and alleviated the wall thickening and changes in mechanical behavior observed in untreated Eln-/- aorta. The changes in thickness and mechanical behavior in captopril-treated Eln-/- aorta were not due to alterations in measured elastin or collagen amounts, but may have been caused by alterations in smooth muscle cell (SMC) properties. We used a constitutive model to understand how changes in stress contributions of each wall component could explain the observed changes in composite mechanical behavior. Our modeling results show that alterations in the collagen natural configuration and SMC properties in the absence of elastin may explain untreated Eln-/- aortic behavior and that partial rescue of the SMC properties may account for captopril-treated Eln-/- aortic behavior.
['Kim|Jungsil|J|', 'Cocciolone|Austin J|AJ|', 'Staiculescu|Marius C|MC|', 'Mecham|Robert P|RP|', 'Wagenseil|Jessica E|JE|http://orcid.org/0000-0001-7972-448X']
D000818:Animals D000831:Animals, Newborn D001011:Aorta D001696:Biomechanical Phenomena D001794:Blood Pressure D002216:Captopril D003895:Desmosine D004549:Elastin D016326:Extracellular Matrix Proteins D005786:Gene Expression Regulation D006339:Heart Rate D006352:Heart Ventricles D006909:Hydroxyproline D018345:Mice, Knockout D032389:Myocytes, Smooth Muscle D012333:RNA, Messenger D011945:Receptors, Angiotensin D013314:Stress, Mechanical D066253:Vascular Remodeling
Captopril Elastin Angiotensin II Angiotensin-converting enzyme Arterial development Arterial mechanics Arterial remodeling Extracellular matrix