Estrogen and progesterone induce migration, invasion, and proliferation of vascular smooth muscle cells via matrix metalloproteinase regulation

Recent studies have indicated postmenopausal women receiving hormone replacement therapy (HRT) have more adverse outcomes of peripheral arterial disease after vascular reconstruction, including increased intimal hyperplasia (IH) and restenosis. The major cellular processes contributing to IH pathogenesis are extracellular matrix (ECM) degradation and vascular smooth muscle cell (VSMC) proliferation, migration, and invasion of the ECM. We have previously shown hormone exposure results in unbalanced matrix metalloproteinase (MMP) regulation in VSMCs, a family of ECM degradative enzymes known to play a role in vascular remodeling. Here we examine the role of hormonally-stimulated MMP activity in the regulation of the cellular processes contributing to IH development. Data from the type of analyses presented here could be used to develop a computational model of vascular restenosis focusing on the importance of hormone-modulated VSMC function.