doi: 10.1161/ATVBAHA.108.167403
© 2008 American Heart Association, Inc.
Editorials |
Are the Mechanisms for NO-Dependent Vascular Remodeling Different From Vasorelaxation In Vivo?
From the Vascular Biology and Therapeutics Program, Department of Pharmacology, Yale University School of Medicine, New Haven, Conn.
Correspondence to William C. Sessa, Vascular Biology and Therapeutics Program, Department of Pharmacology, Yale University School of Medicine, Amistad Research Building, 10 Amistad Street, New Haven, CT 06536-0812. E-mail william.sessa@yale.edu
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
The remodeling of blood vessels, characterized by thickening of the vessel wall attributable to neointima formation or changing of the vessel wall thickness and diameter, occurs after injury, dysfunction, or endothelial denudation, resembling the risk associated with endovascular surgery. Upon vascular injury, activated vascular smooth muscle cells (VSMCs) of local or systemic origin contribute to the remodeling processes which may eventually lead to occlusion of the blood vessel.1 Thus, understanding the molecular aspects of occlusive neointimal proliferation is desirable to promote better therapies for this disease process.
See accompanying article on page 1244
There is substantial evidence that endothelial-derived nitric oxide (NO) is a key regulator of vascular remodeling.2,3 Endothelial nitric oxide synthase (eNOS)-derived NO diffuses into the surrounding cell layers of VSMCs to exert various cardiovascular homeostatic functions. eNOS can be stimulated to produce NO by hemodynamic forces, autacoids, hormones, and growth factors. Once NO diffuses into the VSMC layer, NO mediates vasorelaxation but also regulates the balance of VSMC proliferation versus apoptosis, the latter functions governing important aspects of vessel caliber and remodeling.4 Thus, one can envision the endothelium as a sensor that adjusts to changes in blood flow to regulate NO levels which, in turn, triggers relaxation and eventual remodeling responses in the vessel wall. The canonical mechanism (see Figure, left side) by which NO exerts its functions on vessel relaxation is via activation of the soluble guanylyl cyclase (sGC), thereby elevating cyclic guanosine monophosphate (cGMP) levels. cGMP activates cGMP-dependent protein kinase type I (cGKI) which
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