Events Calendar

16 Nov
Event Type

Lectures, Symposia, Etc.

Topic

Research

Target Audience

Faculty, Graduate Students, Postdocs

Department
Department of Mechanical Engineering and Materials Science
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MEMS Graduate Seminar Series - Invited Lecturer - Dr. Susan Lessner

This is a past event.

Vascular Remodeling in Health and Disease: A Different Angle of View

Abstract:

Vascular remodeling has been defined as a long-lasting change in vascular wall geometry and/or composition that occurs in the adult organism. While early investigations of vascular remodeling focused on changes in vessel diameter, wall thickness, or matrix composition resulting from altered blood pressure or wall shear stress, our recent work has examined more subtle alterations in collagen fiber organization and conformation that may reflect changes in the balance of active and passive mechanical stresses.

Methods:  Our recent work has examined vascular remodeling in several rodent models of cardiovascular disease, including the apolipoprotein E (apoE) knockout (KO) mouse, a model widely used in atherosclerosis research, the fibrillin-1 (Fbn1) C1041G heterozygote, a mouse model of Marfan syndrome, and the nitric oxide synthase-3 (NOS3) knockout mouse, a model of endothelial dysfunction leading to hypertension.  We use tools including small animal ultrasound, ex vivo biaxial mechanical testing, and multiphoton second harmonic generation (SHG) microscopy to investigate changes in the biomechanics and structure of the aortic wall over time in normal physiological aging or in response to pathological stimuli such as hypercholesterolemia.

Results:  In the apoE KO mouse, we found that age-related collagen fiber reorientation was altered by high-fat diet, which induces hypercholesterolemia and atherosclerotic lesion development in these mice.  Mice fed a chow diet showed reorientation of adventitial collagen fibers to a more longitudinal average orientation, while animals fed the high-fat diet showed more circumferentially-directed reorientation of collagen fibers by SHG microscopy.  These changes in average fiber orientation were not directly associated with altered volumetric blood flow rates or blood pressure.  In contrast, age-related vascular remodeling in wild type (WT) controls does not lead to significant collagen fiber reorientation, but fibers on average show reduced tortuosity with age. In NOS3 KO mice, endothelial dysfunction resulting from reduction in nitric oxide bioavailability leads to hypertension with aging, as previously reported, while adventitial collagen fibers remodel to a more circumferential average orientation and display reduced tortuosity.  This fiber reorientation is accompanied by increased circumferential stiffness.  Wild type, apoE KO and NOS3 KO mice all demonstrate a reduction in active stress generation with age, suggesting that changes in the balance between active and passive stresses in the vessel wall may contribute to age-related collagen fiber remodeling.

Conclusions:  We have demonstrated in several mouse models that vascular remodeling involves changes in collagen fiber organization and tortuosity that occur alongside alterations in vessel matrix composition, vessel geometry, and active force generation. These observations raise questions regarding the molecular mechanisms by which matrix turnover and synthesis are coordinated to allow such changes to occur without unduly disrupting vascular function.

Biography:

 

Dr. Susan (‘Sue’) Lessner earned her PhD in Chemical Engineering from MIT in 2000, followed by postdoctoral training in vascular biology in the Galis lab at Emory University School of Medicine, Division of Cardiology.  She established her independent lab at University of South Carolina School of Medicine in 2005, where she has remained for the past 16 years, and was promoted to Professor in 2020.  Dr. Lessner’s research focuses on vascular remodeling and biomechanical failure in multiple pathological conditions, including atherosclerotic plaque rupture, arterial dissection, and aortic aneurysm, primarily using mouse models of cardiovascular disease. Research in the Lessner lab aims to understand both biomechanical and biological factors leading to pathological blood vessel remodeling and failure. Dr. Lessner is currently co-investigator on an NIH R01 that seeks to develop a novel, approach to treat vascular calcification using EDTA-loaded nanoparticles. She collaborates with faculty in Mechanical Engineering to identify material parameters of normal and diseased arterial tissue, and to perform computational simulations of vascular growth and remodeling. Dr. Lessner also has expertise in clinical image analysis, focusing in particular on analysis of vasculature in computed tomographic angiograms (CTAs).  She currently works with several vascular surgeons on studies of carotid artery stenosis and peripheral arterial disease (PAD) in human patients.

Dr. Lessner plays a substantial role in the University of South Carolina Biomedical Engineering program. Among other activities, she has directed the graduate Anatomy and Physiology for Biomedical Engineers course and currently serves on the BMEN Graduate Committee.  In addition, she teaches a workshop in quantitative CTA analysis for third-year medical students.

Tuesday, November 16 at 11:00 a.m. to 12:00 p.m.

Benedum Hall, 102
3700 O'Hara Street, Pittsburgh, PA 15261

MEMS Graduate Seminar Series - Invited Lecturer - Dr. Susan Lessner

Vascular Remodeling in Health and Disease: A Different Angle of View

Abstract:

Vascular remodeling has been defined as a long-lasting change in vascular wall geometry and/or composition that occurs in the adult organism. While early investigations of vascular remodeling focused on changes in vessel diameter, wall thickness, or matrix composition resulting from altered blood pressure or wall shear stress, our recent work has examined more subtle alterations in collagen fiber organization and conformation that may reflect changes in the balance of active and passive mechanical stresses.

Methods:  Our recent work has examined vascular remodeling in several rodent models of cardiovascular disease, including the apolipoprotein E (apoE) knockout (KO) mouse, a model widely used in atherosclerosis research, the fibrillin-1 (Fbn1) C1041G heterozygote, a mouse model of Marfan syndrome, and the nitric oxide synthase-3 (NOS3) knockout mouse, a model of endothelial dysfunction leading to hypertension.  We use tools including small animal ultrasound, ex vivo biaxial mechanical testing, and multiphoton second harmonic generation (SHG) microscopy to investigate changes in the biomechanics and structure of the aortic wall over time in normal physiological aging or in response to pathological stimuli such as hypercholesterolemia.

Results:  In the apoE KO mouse, we found that age-related collagen fiber reorientation was altered by high-fat diet, which induces hypercholesterolemia and atherosclerotic lesion development in these mice.  Mice fed a chow diet showed reorientation of adventitial collagen fibers to a more longitudinal average orientation, while animals fed the high-fat diet showed more circumferentially-directed reorientation of collagen fibers by SHG microscopy.  These changes in average fiber orientation were not directly associated with altered volumetric blood flow rates or blood pressure.  In contrast, age-related vascular remodeling in wild type (WT) controls does not lead to significant collagen fiber reorientation, but fibers on average show reduced tortuosity with age. In NOS3 KO mice, endothelial dysfunction resulting from reduction in nitric oxide bioavailability leads to hypertension with aging, as previously reported, while adventitial collagen fibers remodel to a more circumferential average orientation and display reduced tortuosity.  This fiber reorientation is accompanied by increased circumferential stiffness.  Wild type, apoE KO and NOS3 KO mice all demonstrate a reduction in active stress generation with age, suggesting that changes in the balance between active and passive stresses in the vessel wall may contribute to age-related collagen fiber remodeling.

Conclusions:  We have demonstrated in several mouse models that vascular remodeling involves changes in collagen fiber organization and tortuosity that occur alongside alterations in vessel matrix composition, vessel geometry, and active force generation. These observations raise questions regarding the molecular mechanisms by which matrix turnover and synthesis are coordinated to allow such changes to occur without unduly disrupting vascular function.

Biography:

 

Dr. Susan (‘Sue’) Lessner earned her PhD in Chemical Engineering from MIT in 2000, followed by postdoctoral training in vascular biology in the Galis lab at Emory University School of Medicine, Division of Cardiology.  She established her independent lab at University of South Carolina School of Medicine in 2005, where she has remained for the past 16 years, and was promoted to Professor in 2020.  Dr. Lessner’s research focuses on vascular remodeling and biomechanical failure in multiple pathological conditions, including atherosclerotic plaque rupture, arterial dissection, and aortic aneurysm, primarily using mouse models of cardiovascular disease. Research in the Lessner lab aims to understand both biomechanical and biological factors leading to pathological blood vessel remodeling and failure. Dr. Lessner is currently co-investigator on an NIH R01 that seeks to develop a novel, approach to treat vascular calcification using EDTA-loaded nanoparticles. She collaborates with faculty in Mechanical Engineering to identify material parameters of normal and diseased arterial tissue, and to perform computational simulations of vascular growth and remodeling. Dr. Lessner also has expertise in clinical image analysis, focusing in particular on analysis of vasculature in computed tomographic angiograms (CTAs).  She currently works with several vascular surgeons on studies of carotid artery stenosis and peripheral arterial disease (PAD) in human patients.

Dr. Lessner plays a substantial role in the University of South Carolina Biomedical Engineering program. Among other activities, she has directed the graduate Anatomy and Physiology for Biomedical Engineers course and currently serves on the BMEN Graduate Committee.  In addition, she teaches a workshop in quantitative CTA analysis for third-year medical students.

Tuesday, November 16 at 11:00 a.m. to 12:00 p.m.

Benedum Hall, 102
3700 O'Hara Street, Pittsburgh, PA 15261

Topic

Research

Target Audience

Faculty, Graduate Students, Postdocs

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