Investigating the Role of Phosphodiesterase 1C in Vascular Smooth Muscle Cell Migration and Invasion
type: CreativeWork
description: Phenotypic plasticity of human arterial smooth muscle cells (HASMCs) allows them to transition from a “contractile/quiescent” state, in which they regulate arterial tone and blood pressure, to one in which these cells are more “synthetic/activated”. Synthetic/activated HASMCs are migratory and proliferative, and these capabilities allow them to participate in vasculogenesis during development, as well as post-natal vessel repair. Although several laboratories have investigated the overall inhibitory influence of cAMP-elevating agents on HASMC migration, few have addressed whether cAMP signalling also coordinates HASMC invasion of extracellular matrices, a critical first step in HASMC migration in vivo. Indeed, while several cAMP-elevating agents reduce intimal hyperplasia/hypertrophy in animal models, it is presently unclear whether these effects are due to reduced matrix invasion of these cells or solely to inhibition of their migratory capacity. Previous work conducted by our group and others have identified the critical role of cyclic nucleotide phosphodiesterase 1C (PDE1C) in HASMC migration, proliferation, and extracellular matrix adhesion. Here, we directly tested the hypothesis that cAMP signaling, and specifically PDE1C, influences the ability of activated/synthetic HASMCs to invade matrix in 3-dimensions (3D) and show that this effect is distinct from their migratory actions. Overall, we observed that inhibiting PDE1C activity reduced invasion of 3D collagen matrices by these cells to a greater degree than it did migration in systems not requiring invasion. Using a spheroid model, it was found that either inhibition of PDE1, or the selective silencing of PDE1C, reduced the distance of sprout outgrowth. Of importance in assessing how PDE1C regulates matrix invasion, we investigated whether HASMCs invading collagen matrices generated matrix degrading structures, specifically podosomes. Our data, although preliminary, is consistent with this idea. Similarly, i…
abstract: Phenotypic plasticity of human arterial smooth muscle cells (HASMCs) allows them to transition from a “contractile/quiescent” state, in which they regulate arterial tone and blood pressure, to one in which these cells are more “synthetic/activated”. Synthetic/activated HASMCs are migratory and proliferative, and these capabilities allow them to participate in vasculogenesis during development, as well as post-natal vessel repair. Although several laboratories have investigated the overall inhibitory influence of cAMP-elevating agents on HASMC migration, few have addressed whether cAMP signalling also coordinates HASMC invasion of extracellular matrices, a critical first step in HASMC migration in vivo. Indeed, while several cAMP-elevating agents reduce intimal hyperplasia/hypertrophy in animal models, it is presently unclear whether these effects are due to reduced matrix invasion of these cells or solely to inhibition of their migratory capacity. Previous work conducted by our group and others have identified the critical role of cyclic nucleotide phosphodiesterase 1C (PDE1C) in HASMC migration, proliferation, and extracellular matrix adhesion. Here, we directly tested the hypothesis that cAMP signaling, and specifically PDE1C, influences the ability of activated/synthetic HASMCs to invade matrix in 3-dimensions (3D) and show that this effect is distinct from their migratory actions. Overall, we observed that inhibiting PDE1C activity reduced invasion of 3D collagen matrices by these cells to a greater degree than it did migration in systems not requiring invasion. Using a spheroid model, it was found that either inhibition of PDE1, or the selective silencing of PDE1C, reduced the distance of sprout outgrowth. Of importance in assessing how PDE1C regulates matrix invasion, we investigated whether HASMCs invading collagen matrices generated matrix degrading structures, specifically podosomes. Our data, although preliminary, is consistent with this idea. Similarly, i…
author: Jacobs, Ariana
language: eng
keywords: PDE1C, Migration, Invasion, Spheroids, Cyclic Nucleotide Phosphodiesterase, Vascular, Smooth Muscle Cell
date modified: 2026-07-27T20:35:39Z
provider: Queens University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Queens University

PropertyValue
property ID: Handle
value: http://hdl.handle.net/1974/24977