Chapter 96 - Molecular Pathways of Smooth Muscle Disease

Abstract

Phenotypic modulation of smooth muscle is a hallmark of many disease processes. External environmental stimuli can cause SMCs to lose their contractile properties and become migratory, proliferative, secretory, and sometimes proinflammatory. The molecular mechanisms that underlie each of these functions are comprised of distinct, integrated signaling pathways that coordinate the response of the cell to its environment. Receptor tyrosine kinases and G-protein-coupled receptors activate a series of kinases and phosphatases, as well as NADPH oxidases, that converge on the cytoskeleton and cell cycle to promote migration and proliferation. Proinflammatory cytokines signal through transcription factors such as NF-κB to induce expression of inflammatory genes and adhesion molecules, exacerbating inflammation. Understanding these pathways is key to developing specific therapeutic strategies to interfere only with those functions of smooth muscle that contribute to disease development.