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The Impact of Inducible Depletion of p62/SQSTM1 from Endothelial Cells on Mesenteric and Cerebral Artery Reactivity in Mice.

Semester: Summer 2023

Presentation description

The prevalence of cardiovascular disease (CVD) is higher in residents of rural vs. urban communities, and in older vs. younger individuals. Precise mechanisms responsible for CVD are elusive, and the need for new and novel therapeutic interventions is urgent. Autophagy is a conserved process whereby damaged and dysregulated intracellular proteins are identified, tethered, and escorted to the lysosome for degradation and recycling. Emerging evidence indicates that autophagy is important in maintaining endothelial cell (EC) proteostasis and function. For example, my laboratory showed that: (i) autophagy repression specifically in ECs of adult mice produces arterial dysfunction; and (ii) indexes of autophagy are repressed in ECs of older vs. adult mice and humans that display concurrent EC dysfunction. Sequestosome 1 (p62) tethers proteins targeted for degradation and enables their entry into the autophagic pathway. The contribution from EC p62 to arterial function is unknown. To address this, p62 will be depleted from ECs of adult male and female mice (KO) using genetic procedures, and results will be compared to animals wherein EC p62 is intact (CON). The efficacy and specificity of EC p62 depletion will be evaluated in both groups by measuring p62 mRNA (qPCR) and protein (immunoblotting) expression in ECs and vascular smooth muscle. At tissue collection: (i) contraction to non-receptor (potassium chloride) and α-1 receptor (phenylephrine) mediated agonists, and relaxation to endothelium-dependent (acetylcholine) and independent (sodium nitroprusside) stimuli, will be measured using isometric (mesenteric arteries) and isobaric (cerebral arteries) approaches; and (ii) intravascular signaling pathways (immunoblotting) important to vasorelaxation will be assessed in both groups. Our findings will define the contribution from EC p62 to mesenteric and cerebral arterial function.

Presenter Name: Colton Gardner

Presentation Type: Poster
Presentation Format: Virtual
Presentation #69
College: Health
School / Department: Nutrition and Integrative Physiology
Research Mentor: J. David Symons
Date | Time: Thursday, Aug 3rd | 9:00 AM