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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:471.)
© 2001 American Heart Association, Inc.

Editorial

Role of Reactive Oxygen Species in Angiotensin II Signaling

The Plot Thickens

George A. Stouffer; Cam Patterson; N. Madamanchi; Marschall S. Runge

From the Division of Cardiology, University of North Carolina , Chapel Hill.

Correspondence to Marschall S. Runge, MD, PhD, Chairman, Department of Medicine, University of North Carolina at Chapel Hill, 3033 Old Clinic Building, Campus Box 7005, Chapel Hill, NC 27599-7005. E-mail mrunge@med.unc.edu

Key Words: reactive oxygen species • angiotensin II • antioxidants • smooth muscle cells

Angiotensin II (Ang II) is the dominant effector of the renin-angiotensin system. In addition to its well-known hemodynamic and endocrine effects, Ang II regulates the cardiovascular remodeling associated with hypertension, atherosclerosis, heart failure, and diabetes mellitus. The importance of Ang II in cardiovascular disease states is highlighted by the prominent role that ACE inhibitors and angiotensin receptor blockers play in cardiovascular medicine. These drugs reduce clinical events and improve survival in patients with vascular disease or congestive heart failure and are among the most widely used medications in the world.^{1 2}

There is accumulating evidence that Ang II has direct effects on smooth muscle cells (SMCs) that contribute to abnormalities ranging from subtle vascular dysfunction to severe atherosclerosis, ischemia, and necrosis. Ang II stimulates proliferation, hypertrophy, and migration of cultured vascular SMCs (VSMCs) via binding to the angiotensin type 1 (AT₁) receptor.³ This receptor is a member of the superfamily of 7 transmembrane–spanning, G protein–coupled cell surface receptors (GPCRs). Traditionally, these receptors were thought to elicit intracellular signaling solely via activation of heterotrimeric G proteins, but more recent evidence has demonstrated the importance of tyrosine phosphorylation of various signaling proteins, including tyrosine kinase receptors.

Transactivated epidermal growth factor (EGF) receptor (EGFR) serves as a scaffold for the assembly of protein-signaling complexes in VSMCs. EGFR is transactivated by many GPCRs in various cell types, suggesting an important role in GPCR signaling. In VSMCs, activation of AT₁ induces calcium-dependent transactivation of EGFR, which serves as a scaffold for c-src and downstream adaptors . . . [Full Text of this Article]

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