ABSTRACT
Coronary artery disease (CAD) is the number one cause of death among men and women in the USA. Genetic predisposition and environmental factors lead to the development of atherosclerotic plaques in the vessel walls of the coronary arteries, resulting in decreased myocardial perfusion. Treatment includes a combination of revascularization procedures and medical therapy. Because of the high surgical risk of many of the patients undergoing revascularization procedures, medical therapies to reduce ischemic disease are an area of active research. Small molecule, cytokine, endothelial progenitor cell, stem cell, gene, and mechanical therapies show promise in increasing the collateral growth of blood vessels, thereby reducing myocardial ischemia.
Subject(s)
Angiogenesis Inducing Agents/therapeutic use , Coronary Artery Disease/therapy , Coronary Vessels/drug effects , Genetic Therapy/methods , Neovascularization, Physiologic/drug effects , Stem Cell Transplantation/methods , Angiogenesis Inducing Agents/adverse effects , Animals , Collateral Circulation/drug effects , Coronary Artery Disease/genetics , Coronary Artery Disease/metabolism , Coronary Artery Disease/physiopathology , Coronary Circulation/drug effects , Coronary Vessels/metabolism , Coronary Vessels/pathology , Coronary Vessels/physiopathology , Genetic Therapy/adverse effects , Humans , Molecular Targeted Therapy , Neovascularization, Physiologic/genetics , Recovery of Function , Signal Transduction/drug effects , Stem Cell Transplantation/adverse effects , Treatment OutcomeABSTRACT
Thrombin signaling in the endothelium is linked to multiple phenotypic changes, including alterations in permeability, vasomotor tone, and leukocyte trafficking. The thrombin signal is transduced, at least in part, at the level of gene transcription. In this review, we focus on the role of thrombin signaling and transcriptional networks in mediating downstream gene expression and endothelial phenotype. In addition, we report the results of DNA microarrays in control and thrombin-treated endothelial cells. We conclude that (1) thrombin induces the upregulation and downregulation of multiple genes in the endothelium, (2) thrombin-mediated gene expression involves a multitude of transcription factors, and (3) future breakthroughs in the field will depend on a better understanding of the spatial and temporal dynamics of these transcriptional networks.
