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Document Type
Oral Presentation
Department
Biomedical Science and Engineering
Faculty Mentor
David Champlin PhD, Lucy Liaw PhD
Keywords
Cardiovascular Disease, Aorta, Perivascular Adipose Tissue (PVAT), RAB27a
Abstract
Perivascular adipose tissue (PVAT) is a specialized adipose depot that surrounds the vasculature. In healthy conditions, PVAT exhibits a thermogenic phenotype, denoted by high metabolic activity, while exhibiting a lipid storage phenotype under obese conditions. While the thermogenic PVAT promotes anti-inflammation and vasodilation of blood vessels, the lipid storage phenotype increases the progression of cardiovascular disease by inducing inflammation and vasoconstriction. Ras related protein Rab-27A (RAB27a) is a trafficking protein that regulates exosome secretion and we have shown its expression is upregulated in the PVAT of obese mice. However, whether changes in RAB27a expression during obesity mediates the phenotypic change in PVAT is unclear. We hypothesize that loss of RAB27a expression during obesity will preserve the thermogenic phenotype of PVAT.
To test our hypothesis, we quantified lipid accumulation differences in multiple adipose depots between wildtype and Rab27a global null mice fed a high fat diet (HFD) or sucrose-controlled diet (SCD). Additionally, changes in vascular morphology between our groups was examined by quantifying the total, lumenal, and medial area of transverse slices of thoracic aorta. To evaluate the impact of these changes on vasoreactivity, wire myography studies were completed to quantify changes in vascular contraction. These data show that diet, not the loss of RAB27a, affects lipid accumulation. However, Rab27a null mice have a smaller lumenal, medial, and total area of the aorta, regardless of diet. Additionally, Rab27a null mice fed a HFD showed increased contraction compared to control groups. These data suggest that RAB27a is a regulator of vascular contractility.
Evaluating whether RAB27a loss impacts PVAT and aorta morphology during a HFD
Perivascular adipose tissue (PVAT) is a specialized adipose depot that surrounds the vasculature. In healthy conditions, PVAT exhibits a thermogenic phenotype, denoted by high metabolic activity, while exhibiting a lipid storage phenotype under obese conditions. While the thermogenic PVAT promotes anti-inflammation and vasodilation of blood vessels, the lipid storage phenotype increases the progression of cardiovascular disease by inducing inflammation and vasoconstriction. Ras related protein Rab-27A (RAB27a) is a trafficking protein that regulates exosome secretion and we have shown its expression is upregulated in the PVAT of obese mice. However, whether changes in RAB27a expression during obesity mediates the phenotypic change in PVAT is unclear. We hypothesize that loss of RAB27a expression during obesity will preserve the thermogenic phenotype of PVAT.
To test our hypothesis, we quantified lipid accumulation differences in multiple adipose depots between wildtype and Rab27a global null mice fed a high fat diet (HFD) or sucrose-controlled diet (SCD). Additionally, changes in vascular morphology between our groups was examined by quantifying the total, lumenal, and medial area of transverse slices of thoracic aorta. To evaluate the impact of these changes on vasoreactivity, wire myography studies were completed to quantify changes in vascular contraction. These data show that diet, not the loss of RAB27a, affects lipid accumulation. However, Rab27a null mice have a smaller lumenal, medial, and total area of the aorta, regardless of diet. Additionally, Rab27a null mice fed a HFD showed increased contraction compared to control groups. These data suggest that RAB27a is a regulator of vascular contractility.
