Vascular Smooth Muscle

S mooth muscle cells are important sources of interleukins, chemokines and growth factors in several organ systems. Proinflammatory, mitogenic, and promigratory stimuli produced by vascular and visceral smooth muscle cells may contribute significantly to pathologenesis of atherosclerosis, asthma, inflammatory bowel diseases, and preterm labor. Understanding the role of smooth muscle cells as sources of soluble signals may provide new insights into the cause of these chronic debilitating diseases, and may suggest new targets for developing anti-inflammatory therapy. INTRODUCTION The primary function of smooth muscle cells is to change, by contracting and relaxing, the shape and stiffness of hollow organs. By relaxing or contracting, smooth muscle regulates blood flow through the vasculature, airflow in the lungs, movement of food and waste through the gut, and uterine delivery of neonates. The neurotransmitters, contractile proteins, and intracellular signaling mechanisms controlling contraction have been studied intensely for many years. We have a good sense of the basic components of the contractile machinery and the regulatory pathways controlling contraction in most autonomic effector organs (Figure 1). It is also clear that smooth muscle cells synthesize extracellular matrix proteins and proteoglycans to fill the extracellular space between muscle cells. In addition to their familiar functions, smooth muscle cells have significant capacity to synthesize, secrete, and respond to small soluble signaling molecules. Data supporting this notion vary among smooth muscle–containing organs; the vasculature has been studied most extensively, although airway smooth muscle and uterine smooth muscle have also received considerable attention. There is considerably less information regarding gastrointestinal smooth muscle. In any case, smooth muscle cells from many organs respond to proinflammatory stimuli, such as interleukin-(IL)-1␤, IL-5, IL-13 and tissue necrosis factor-(TNF)-␣, by synthesizing a remarkably wide spectrum of signaling proteins including cytokines, chemokines, and peptide growth factors. Smooth muscle cells are thus active, important components of the immune response in the vasculature, the airways, the gastrointestinal system, and the uterus. Figure 2 summarizes the effects of proinflammatory stimuli on the expression of many of these signaling proteins in smooth muscle cells and indicates relevant signal transduction pathways, which involve several mitogen-activated protein kinases; among these are the extracellular signal–regulated kinase (ERK1/2), p38, c-Jun N-terminal kinase (JNK), and the Janus protein tyrosine kinases (JAK). Activation of these kinase pathways by proinflammatory stimuli, as well as by increases in intracellular Ca 2+ within smooth muscle cells, activates multiple transcription factors, including nuclear factor-(NF)-␬B, signal transducers and activators of …