Redox control of growth factor signaling: recent advances in cardiovascular medicine

Growth factors play vital roles in the regulation of various biologic processes, including those in cardiovascular and respiratory systems. Accumulating evidence suggests that reactive oxygen species mediate growth factor signal transduction. The discovery of reactive oxygen species production by angiotensin II in vascular smooth muscle cells via the activation of NAD(P)H oxidase promoted studies of redox control of growth factor signaling. In the past few years, there have been further advances in this field. In addition to established roles of reactive oxygen species in vascular smooth muscle growth, these species have been demonstrated to serve as second messengers for cardiac hypertrophy induced by angiotensin II. NAD(P)H oxidase also produces reactive oxygen species in response to endothelin-1 in vascular smooth muscle and cardiac muscle cells. These results suggest that inhibiting NAD(P)H oxidase might be a useful therapeutic strategy. In fact, adenovirus-mediated gene transfer appears to be an effective approach to prevent vascular hypertrophy in rodent models. Growth factors also induce survival signaling in cardiac and smooth muscle cells, and redox control may play a role in such events. It is likely that studies reporting the mechanisms of redox control of growth factor signaling will rapidly emerge in the next several years, and understanding of such regulation should help in the development of therapeutic strategies against heart and lung diseases.