Date

5-31-2017

Document Type

Poster

Abstract

Approximately 1 in 3 deaths in the US is caused by cardiovascular diseases, among them atherosclerosis. Atherosclerosis occurs through excessive cholesterol deposition (hyperlipidemia) along the inner layer of the artery called the intima, resulting in plaque formation that blocks arterial blood flow and could lead to heart attacks and strokes. It has recently been recognized that inflammation plays an important role in plaque formation. Specifically, T cell activation can affect the progression of atherosclerosis through interaction with antigen presenting cells (APCs) in a hyperlipidemic environment. APCs ingest foreign objects and present digested remnants on antigen presenting molecules at the cell surface and these complexes are recognized by T cells. Unlike common peptide antigen presenting molecules, group 1 CD1 molecules present both self and pathogenic lipids to T cells. This study looks at the unknown role of lipid antigen presenting molecules, specifically CD1b and CD1c subset molecules, on atherosclerotic plaque formation around the intima of hearts in new mice models: control LDL receptor knockout mice (LDLrko), LDL receptor knockout mice with hCD1 transgene (hCD1Tg/LDLrko), LDL receptor and CD1d knockout mice with hCD1 transgene (hCD1Tg/CD1dko/LDLrko), and LDL receptor inactivated mice with hCD1and HJ1 transgenes (hCD1Tg/ HJ1Tg/LDLrko).The results of this study indicate that hCD1Tg/CD1dko/LDLrko group had the highest plaque area with an average of 1,268,144.03 +/- 196,133.22 um2. Compared to the control mouse strain (LDLrko) with an average plaque area of 920,032.71 +/- 176,399.84 um2, both hCD1Tg/LDLrko and hCD1Tg/ HJ1Tg/LDLrko mice had lower average plaque areas (816,594.55 +/- 292,567.95 and 555,188.84 +/- 171,016.61 um2, respectively). One-way ANOVA and Turkey post-hoc statistical tests were performed using Prism Software. It is unclear whether the HJ1 T cell receptors were activated by the amount of plaque upon the end of the 12-week high fat diet period. Further research with an extended high fat diet period (16-18 weeks) can determine whether HJ1 T cell receptors are activated in hyperlipidemic mice. Future clinical uses of this research may include manipulating the group 1 CD1-restricted T cells to control heart plaque formation and, possibly, preventing atherosclerosis and heart attacks.

Major

Biological Sciences

Major / Minor

Psychology

College / School

Weinberg College of Arts and Sciences

O.U.R. Funding

yes

Faculty Advisor

Chyung-Ru Wang

doi

https://doi.org/10.21985/N2F59P

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May 31st, 12:00 AM

The Effect of Group 1 CD1-restricted T cells on Atherosclerosis

Approximately 1 in 3 deaths in the US is caused by cardiovascular diseases, among them atherosclerosis. Atherosclerosis occurs through excessive cholesterol deposition (hyperlipidemia) along the inner layer of the artery called the intima, resulting in plaque formation that blocks arterial blood flow and could lead to heart attacks and strokes. It has recently been recognized that inflammation plays an important role in plaque formation. Specifically, T cell activation can affect the progression of atherosclerosis through interaction with antigen presenting cells (APCs) in a hyperlipidemic environment. APCs ingest foreign objects and present digested remnants on antigen presenting molecules at the cell surface and these complexes are recognized by T cells. Unlike common peptide antigen presenting molecules, group 1 CD1 molecules present both self and pathogenic lipids to T cells. This study looks at the unknown role of lipid antigen presenting molecules, specifically CD1b and CD1c subset molecules, on atherosclerotic plaque formation around the intima of hearts in new mice models: control LDL receptor knockout mice (LDLrko), LDL receptor knockout mice with hCD1 transgene (hCD1Tg/LDLrko), LDL receptor and CD1d knockout mice with hCD1 transgene (hCD1Tg/CD1dko/LDLrko), and LDL receptor inactivated mice with hCD1and HJ1 transgenes (hCD1Tg/ HJ1Tg/LDLrko).The results of this study indicate that hCD1Tg/CD1dko/LDLrko group had the highest plaque area with an average of 1,268,144.03 +/- 196,133.22 um2. Compared to the control mouse strain (LDLrko) with an average plaque area of 920,032.71 +/- 176,399.84 um2, both hCD1Tg/LDLrko and hCD1Tg/ HJ1Tg/LDLrko mice had lower average plaque areas (816,594.55 +/- 292,567.95 and 555,188.84 +/- 171,016.61 um2, respectively). One-way ANOVA and Turkey post-hoc statistical tests were performed using Prism Software. It is unclear whether the HJ1 T cell receptors were activated by the amount of plaque upon the end of the 12-week high fat diet period. Further research with an extended high fat diet period (16-18 weeks) can determine whether HJ1 T cell receptors are activated in hyperlipidemic mice. Future clinical uses of this research may include manipulating the group 1 CD1-restricted T cells to control heart plaque formation and, possibly, preventing atherosclerosis and heart attacks.