The elastic properties of conducting vessels in vertebrates are determined, to a major extent, by the ratio of elastin to collagen. Under normal conditions, this ratio is dictated by the need to maintain the elastic modulus in a range that is best able to provide capacitance and pulse smoothing in a pulsatile circulatory system. This elastic modulus can change as a result of aging or disease through the loss of elastin or an increase in collagen. The consequences are a stiffening and dilation of the vessel and loss of its ability to dampen the pulsations in blood flow. Changes in blood flow and pressure result, with hypertension being a biomarker for altered vessel function. This proposal is organized around understanding the relationship between arterial stiffening and blood pressure changes.
Aim 1 will take advantage of mice where the elastin/collagen ratio has been reduced by inactivation of one copy of the elastin gene to study the relationship between arterial stiffening and the development of hypertension.
Aim 2 will employ conditional and inducible elastin transgenes to change the elastic properties of the vessel wall at different times to investigate the reversibility of stiffness-related hypertension.
Aim 3 will utilize gene expression profiling to identify individual genes, gene sets, and molecular pathways that change in response to vessel stiffness and alterations in blood pressure.
Aim 4 will pursue several treatment strategies that modulate blood pressure and alter vessel compliance.

Public Health Relevance

This project seeks to elucidate the mechanisms that lead to conduit artery stiffening in the context of hypertension and explore the temporal relationship between arterial stiffening and the development of hypertension in animal models.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZHL1-CSR-W (S1))
Program Officer
OH, Youngsuk
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Washington University
Anatomy/Cell Biology
Schools of Medicine
Saint Louis
United States
Zip Code
Walji, Tezin A; Turecamo, Sarah E; DeMarsilis, Antea J et al. (2016) Characterization of metabolic health in mouse models of fibrillin-1 perturbation. Matrix Biol 55:63-76
Walji, Tezin A; Turecamo, Sarah E; Sanchez, Alejandro Coca et al. (2016) Marrow Adipose Tissue Expansion Coincides with Insulin Resistance in MAGP1-Deficient Mice. Front Endocrinol (Lausanne) 7:87
Maedeker, Justine A; Stoka, Kellie V; Bhayani, Siddharth A et al. (2016) Hypertension and decreased aortic compliance due to reduced elastin amounts do not increase atherosclerotic plaque accumulation in Ldlr-/- mice. Atherosclerosis 249:22-9
Balestrini, Jenna L; Gard, Ashley L; Gerhold, Kristin A et al. (2016) Comparative biology of decellularized lung matrix: Implications of species mismatch in regenerative medicine. Biomaterials 102:220-30
Lee, Vivian S; Halabi, Carmen M; Hoffman, Erin P et al. (2016) Loss of function mutation in LOX causes thoracic aortic aneurysm and dissection in humans. Proc Natl Acad Sci U S A 113:8759-64
Balestrini, Jenna L; Liu, Angela; Gard, Ashley L et al. (2016) Sterilization of Lung Matrices by Supercritical Carbon Dioxide. Tissue Eng Part C Methods 22:260-9
Walker, Ashley E; Henson, Grant D; Reihl, Kelly D et al. (2015) Greater impairments in cerebral artery compared with skeletal muscle feed artery endothelial function in a mouse model of increased large artery stiffness. J Physiol 593:1931-43
Kim, Jungsil; Wagenseil, Jessica E (2015) Bio-Chemo-Mechanical Models of Vascular Mechanics. Ann Biomed Eng 43:1477-87
Guzy, Robert D; Stoilov, Ivan; Elton, Timothy J et al. (2015) Fibroblast growth factor 2 is required for epithelial recovery, but not for pulmonary fibrosis, in response to bleomycin. Am J Respir Cell Mol Biol 52:116-28
Mecham, Robert P; Gibson, Mark A (2015) The microfibril-associated glycoproteins (MAGPs) and the microfibrillar niche. Matrix Biol 47:13-33

Showing the most recent 10 out of 40 publications