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(Circulation Research. 2002;91:273.)
© 2002 American Heart Association, Inc.

Editorials

Phosphatidylinositol 3-Kinase

A Key Regulator of Vascular Tone?

Masataka Sata, Ryozo Nagai

From the Department of Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine, Tokyo, Japan.

Correspondence to Dr Ryozo Nagai, Department of Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. E-mail nagai-tky@umin.ac.jp

Key Words: phosphatidylinositol 3-kinase • Akt • hypertension • smooth muscle • endothelial cells

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The pathogenesis of essential hypertension is multifactorial. Although the cause of elevated arterial pressure is unknown in most cases, the fundamental hemodynamic abnormality in hypertension is increased peripheral resistance primarily due to changes in vascular structure and function.¹ These changes include arterial wall thickening and abnormal vascular tone, which are modulated by complex interactions between susceptibility genes and environmental factors influencing neural, humoral, cellular, and subcellular mechanisms. While essential hypertension likely has a number of distinct causes, identification of a common feature of hypertension may provide a useful target to treat the disease. The present study by Northcott et al² in this issue of Circulation Research reports an alternation in an intracellular signaling that may contribute to deregulated vascular tone and remodeling during hypertension.

PI3K Signal Transduction Pathway

In the last few years, the PI3K signal transduction pathway has emerged as one of the main signal routes that coordinate complex events leading to changes in cell metabolism, cell growth, cell movement, and cell survival.³ Growth factors, cytokines, and insulin, as well as attachment of cells to the extracellular matrix, stimulate the recruitment of a family of lipid kinases known as phosphoinositide 3-kinase (PI3K) to the plasma membrane (Figure).^3,4 The activated PI3K converts the plasma membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP₂) to phosphatidylinositol-3,4,5-triphosphate (PIP₃).⁴ Signaling proteins with pleckstrin-homology (PH) domains, such as the serine/threonine protein kinases, protein kinase B (PKB, also known as Akt), phosphoinositide-dependent kinase-1 (PDK-1) and PDK-2, accumulate at sites of PI3K activation.^3,5 Association with PIP₃ at the membrane brings . . . [Full Text of this Article]

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