Abstract 16749: Influence of Dual-Specificity Protein Phosphatase 5 on Structural and Mechanical Properties of Rat Middle Cerebral Artery

Abstract

Dual-specificity protein phosphatase 5 (DUSP5) is a multifunctional phosphatase that modulates signaling cascades by catalyzing the dephosphorylation of both threonine and tyrosine residues. We recently reported that KO of Dusp5 enhances cerebral and renal hemodynamics and cognitive function. This effect is associated with increased pPKC and pERK1/2 levels in arteries and arterioles of the brain and kidneys. Further, we found that KO of Dusp5 contributes to the regulation of arteriolar passive mechanical properties with higher myogenic tones, better distensibility, greater compliance, and less stiffness. The present study focuses on the structural and mechanical properties of rat middle cerebral artery (MCA) to evaluate whether it contributes to enhanced vascular and cognitive function in Dusp5 KO rats. Vascular smooth muscle cell layer numbers and collagen content in the wall of the MCA are similar in Dusp5 KO and control rats. While external elastic lamina was absent in the MCA in both strains, internal elastic lamina was thicker in the MCA of Dusp5 KO vs. control rats (2.33 ± 0.02 vs. 1.85 ± 0.03 μm) and associated with higher autofluorescence intensity (953.76 ± 10.03 vs. 737.31 ± 64.88 au), smaller fenestrae areas (51.31 ± 3.62 vs. 70.46 ± 2.24), and fewer number of fenestrations (138.19 ± 8.86 vs. 374.73 ± 17.02 μm 2 ). Even though the myogenic tone is enhanced in Dusp5 KO vs. control rats (52.37 ± 1.65 vs. 44.87 ± 2.00%), other passive mechanical properties (wall thickness, cross-sectional area, wall-to-lumen ratio, wall tension, distensibility, incremental distensibility, circumferential wall strain, circumferential wall stress, and elastin modulus) of the MCA of Dusp5 KO rats do not exhibit significant changes. The findings suggest that while Dusp5 KO has a limited impact on changing the structural and mechanical properties of the MCA, its role in enhancing hemodynamics and cognitive function is primarily attributed to its enzymatic function.