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Ann Thorac Surg 2007;84:552
© 2007 The Society of Thoracic Surgeons
Department of Cardiology, Johns Hopkins University School of Medicine, Division of Cardiology, Carnegie 568, 600 N Wolfe St, Baltimore, MD 21287
(Email: nkapur3{at}jhmi.edu).
Zhao and colleagues [1] evaluated the use of engineered endothelial progenitor cells (EPCs) as a delivery tool for localized expression of prepro-calcitonin gene-related peptide (CGRP) in an animal model of shunt-induced pulmonary hypertension. The authors found that treatment with CGRP-expressing EPCs (CGRP-EPC) attenuated increases in total pulmonary resistance (TPR) and mean pulmonary artery pressure induced by aorto-caval shunts. A secondary finding of the study was a reduction in small pulmonary artery wall thickness after treatment with EPCs and CGRP-EPCs.
Previous studies have used adenoviral gene transfer of CGRP to induce pulmonary vasorelaxation and attenuate increases in pulmonary vascular resistance, right ventricular mass, and pulmonary vascular remodeling in chronically hypoxic mice without influencing systemic arterial pressure. Similarly, the anti-proliferative effect of CGRP on aortic and pulmonary smooth muscle cells is well documented. The novelty of this study is the use of engineered cell therapy to modulate pulmonary hemodynamics and vascular remodeling in pulmonary hypertension. Although the findings are exciting, the results are tempered by the inherent insensitivity of hemodynamic measurements in a small animal model of pulmonary hypertension. For example, small changes in injectate volume, thermistor positioning, and changes in body temperature may limit interpretations of cardiac output and quantitation of shunt severity. Furthermore, the benefits of EPC injection alone on TPR are well documented in this study and suggest an effect independent of CGRP. This finding is bolstered by recent data showing beneficial effects of autologous EPC transplantation in patients with idiopathic pulmonary hypertension [2]. Notably, CGRP exerts a positive inotropic effect on myocardial tissue and may improve pulmonary hemodynamics by modulating right ventricular remodeling and function. No data is provided in this article regarding the impact of EPC and CGRP-EPC treatment on changes in right ventricular structure or function. Along these lines, incorporation of EPCs in cardiac tissue may represent another mechanism explaining stabilized hemodynamics in volume-overload induced pulmonary hypertension.
In an era of cell therapy, the promise of cytoengineering is an exciting avenue that uses localized paracrine release of factors designed to ameliorate a particular disease condition. Pulmonary hypertension represents an ideal target for cytotherapy as cells introduced into the venous system have reduced systemic expression and perhaps an associated reduction in systemic toxicity. Zhao and colleagues [1] have successfully "opened one door leading to ten more" in the burgeoning field of cytoengineering.
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