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(Circulation. 2000;101:839.)
© 2000 American Heart Association, Inc.

Editorials

New Approaches to Pulmonary Hypertension

Will Therapies in Mice Work in Humans?

Elizabeth G. Nabel, MD

From the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.

Correspondence to Elizabeth G. Nabel, MD, National Institutes of Health, NHLBI, Building 10/Room 8C103, Bethesda, MD 20892. E-mail enabel@nih.gov

Key Words: Editorials • hypertension, pulmonary • gene therapy

Gene manipulation in mice is now a routine approach to the investigation of disease pathophysiology. Examination of cardiovascular physiology in mice have required the development of miniaturized hemodynamic monitoring systems, or essentially mouse "cath labs," in which catheters and guidewires are manipulated in mouse vessels often <1 mm in size. Cardiovascular integrative physiology has become miniaturized in scale but magnified in impact. Studies testing the pharmacological or physiological effects of infused drugs, which once could be done only in large animals, are now performed in mice by genetic manipulation and/or gene transfer, with equally rigorous hemodynamic monitoring. The potential for defining disease pathophysiology and developing new therapies is enormous.

Given these advances in technology, what have we learned about cardiovascular biology from mouse models? And importantly, will we be able to translate these discoveries into novel therapies for humans? The study by Champion et al¹ in this issue of Circulation brings these questions under close scrutiny. These investigators examine the function of prepro-calcitonin gene–related peptide (CGRP) in a mouse model of pulmonary hypertension. CGRP is a neuropeptide produced by alternative splicing of the calcitonin gene and is located within nerve fibers of lung airways. CGRP receptors are highly expressed by vascular smooth muscle cells within the pulmonary vasculature. These receptors are regulated by hypoxia.^{2 3} During hypoxic conditions, CGRP levels are reduced and vasoconstriction of pulmonary arteries occurs, leading to pulmonary hypertension and its sequelae on right ventricular mass and function. The mechanism for CGRP mediated vasodilation involves activation of K⁺ . . . [Full Text of this Article]

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