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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1254.)
© 2002 American Heart Association, Inc.

Editorials

Therapeutic Angiogenesis

New Indication for Endothelial NO Synthase Gene Transfer

Zvonimir S. Katusic

From the Departments of Anesthesiology and Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minn.

Correspondence to Zvonimir S. Katusic, MD, PhD, Departments of Anesthesiology and Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail katusic.zvonimir@mayo.edu

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

Evidence continues to accumulate on the importance of NO in angiogenesis.^1–7 A number of angiogenic substances, including vascular endothelial growth factor (VEGF), stimulate production of NO in endothelial cells.^8,9 In vivo biosynthesis of NO is essential for angiogenesis induced by tissue ischemia.³ Angiogenesis is severely impaired in ischemic hindlimb of endothelial NO synthase (eNOS)-deficient mice.^3,10 This impairment is not corrected by administration of VEGF, strongly suggesting that NO is downstream signal for angiogenic effect of VEGF. Indeed, in vascular endothelial cells, VEGF increases eNOS enzymatic activity via activation of protein kinase Akt and subsequent phosphorylation of eNOS.^11,12 More recent study demonstrated that 3-hydroxyl-3-methyl coenzyme A (HMG-CoA) reductase inhibitor simvastatin also promotes angiogenesis by activation of protein kinase Akt.¹³ This effect seems to be mediated by stimulation of eNOS enzymatic activity. The importance of protein kinase Akt in regulation of NO production in vivo was demonstrated by adenovirus-mediated delivery of active Akt into the vascular wall. Overexpression of Akt increased resting blood flow, whereas expression of dominant negative Akt inhibited endothelium-dependent relaxation mediated by NO.¹⁴ Thus, phosphorylation of eNOS by protein kinase Akt seems to be a major molecular mechanism underlying the angiogenic effect of VGEF and statins.

See page 1279

Structural adaptation of the vascular tree in response to increased shear stress is of fundamental importance for normal function of cardiovascular system. For instance, exercise training increases cross-sectional area of coronary arteries and stimulates angiogenesis in the heart.¹⁵ This adaptive response appears to be designed to maintain normal shear stress . . . [Full Text of this Article]

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