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The role of fibulin-5 in the growth and remodeling of mouse carotid arteries.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	The role of fibulin-5 in the growth and remodeling of mouse carotid arteries./
Author:	Wan, William.
Description:	183 p.
Notes:	Source: Dissertation Abstracts International, Volume: 73-06, Section: B, page: .
Contained By:	Dissertation Abstracts International73-06B.
Subject:	Engineering, Biomedical. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3500624
ISBN:	9781267212528

The role of fibulin-5 in the growth and remodeling of mouse carotid arteries.
Wan, William.

The role of fibulin-5 in the growth and remodeling of mouse carotid arteries. - 183 p.

Source: Dissertation Abstracts International, Volume: 73-06, Section: B, page: .

Thesis (Ph.D.)--Georgia Institute of Technology, 2011.

The evolution of biomechanical behavior of arteries plays a key role in the on-set and progression of cardiovascular disease. Elevated arterial stiffness, for example, is a key predictor of subsequent cardiovascular events. Arterial stiffening occurs naturally with aging and in disease and is often associated with the loss of functional elastic fiber and increased collagen deposition. Indeed, the biomechanical behavior is governed by the content and organization of the key structural constituents (e.g., collagen, elastin, and smooth muscle) and vessel geometry. The evolution of biomechanical behavior of arteries is governed by biologically-mediated synthesis, degradation, and reorganization of these key structural constituents. A hallmark goal in biomechanics is quantifying the relationship between the microstructure of tissues and their mechanical response throughout tissue growth and remodeling; this will provide a crucial link in understanding the tissue level effects of biological processes involved in disease and normal growth.

ISBN: 9781267212528Subjects--Topical Terms:

845403
Engineering, Biomedical.

The role of fibulin-5 in the growth and remodeling of mouse carotid arteries.
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100 1 $a Wan, William. $3 845552
245 1 4 $a The role of fibulin-5 in the growth and remodeling of mouse carotid arteries.
300 $a 183 p.
500 $a Source: Dissertation Abstracts International, Volume: 73-06, Section: B, page: .
500 $a Adviser: Rudolph L. Gleason, Jr.
502 $a Thesis (Ph.D.)--Georgia Institute of Technology, 2011.
520 $a The evolution of biomechanical behavior of arteries plays a key role in the on-set and progression of cardiovascular disease. Elevated arterial stiffness, for example, is a key predictor of subsequent cardiovascular events. Arterial stiffening occurs naturally with aging and in disease and is often associated with the loss of functional elastic fiber and increased collagen deposition. Indeed, the biomechanical behavior is governed by the content and organization of the key structural constituents (e.g., collagen, elastin, and smooth muscle) and vessel geometry. The evolution of biomechanical behavior of arteries is governed by biologically-mediated synthesis, degradation, and reorganization of these key structural constituents. A hallmark goal in biomechanics is quantifying the relationship between the microstructure of tissues and their mechanical response throughout tissue growth and remodeling; this will provide a crucial link in understanding the tissue level effects of biological processes involved in disease and normal growth.
520 $a Fibulin-5 (fbln5) is an ECM protein that binds tropoelastin and interacts with integrins. Knockout mice lacking fbln5 exhibit loose skin, are prone to pelvic organ prolapse and have tortuous arteries. Mutations of the fbln5 gene are also linked to human diseases such as cutis laxa syndrome, prostate cancer and age-related macular degeneration. Arteries from fbln5 knockout mice lack functional elastic fibers and provide a system for investigating the link between an artery's microstructure and its mechanical response. The overall goal of this project was to develop multi-scaled theoretical and experimental frameworks to quantify the relationship between microstructural content and organization and tissue level material properties of arteries from fbln5 null mice and littermate controls and to quantify the effects of fbln5 on the in vivo maturation of mouse carotid arteries.
520 $a We found that common carotid arteries from adult fbln5 -/- mice exhibited lower in vivo axial stretch and lower in vivo stresses while maintaining a similar compliance over physiological pressures compared to littermate controls. We developed a novel imaging technique to image cells, collagen and elastin in live pressurized and stretched arteries and found that carotid arteries from fbln5 -/- mice lack distinct functional elastic fibers defined by the lamellar structure of alternating layers of smooth muscle cells and elastin sheets. These data suggest that structural differences in fbln5-/- arteries correlate with significant differences in mechanical properties.
520 $a During maturation we found significant differences the in evolution of mechanical and material properties between wildtype and knockout mice. The in vivo axial stretch ratio increased between 3 and 13 weeks in wildtype arteries while in knockout arteries there were no statistically significant differences. In addition, the opening angle of wildtype arteries decreased during maturation while the opening angle of knockout vessels maintained similar levels. During maturation, wildtype vessels experience significant changes in in vivo axial force and compliance while knockout vessels do not undergo such changes. Parameter estimation results suggest that the altered growth and remodeling takes place through changes in material properties as well as through microstructural properties. The results of this study suggest that the lack of fbln5 causes altered material and microstructural properties in mouse carotid arteries, and changes in these properties take place at different time scales.
520 $a In addition, we developed a microstructurally-motivated 3-dimensional (3D) constrained mixture computational framework for vascular growth and remodeling. This model incorporates microstructurally-motivated kinematics and a structurally motivated constitutive equation. We simulated conditions of altered pressure and flow in the presence or absence of elastin turnover, using physiological rates of constituent growth turnover and found that simulated results capture the salient findings found in the literature.
520 $a We measured collagen fiber angles in mouse carotid arteries under various loading conditions, quantified the degree of affine motion exhibited and used the fiber angle distribution in structurally motivated constitutive relations. Incorporating experimentally measured fiber angle data into four-fiber and fiber distribution constitutive relations yielded similar fitting errors; however, when using mean parameters to predict experimental data, the constitutive relation accounting for the entire fiber distribution yielded greater predictive accuracy.
520 $a This dissertation incorporates experimental data quantified at the micro (microstructural-level fiber distributions) and macro (tissue-level mechanical response) scale and incorporates these data into microstructurally motivated constitutive relations. The use of structurally motivated constitutive relations and experimentally measured microstructural data provides a foundation for future work in further understanding the relationship between processes governing microstructure and the tissue level effects of disease and normal growth.
590 $a School code: 0078.
650 4 $a Engineering, Biomedical. $3 845403
650 4 $a Engineering, Mechanical. $3 845387
690 $a 0541
690 $a 0548
710 2 $a Georgia Institute of Technology. $3 845427
773 0 $t Dissertation Abstracts International $g 73-06B.
790 1 0 $a Gleason, Rudolph L., Jr., $e advisor
790 $a 0078
791 $a Ph.D.
792 $a 2011
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