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Eur J Cardiothorac Surg 2004;25:585-590
© 2004 Elsevier Science NL

Perivascular application of C-type natriuretic peptide attenuates neointimal hyperplasia in experimental vein grafts

^a Department of Cardiac Surgery, Innsbruck University Hospital, Anichstrasse 35, A-6020 Innsbruck, Austria
^b Department of Pathology, Innsbruck University Hospital, Anichstrasse 35, A-6020, Innsbruck, Austria

Received 17 March 2003; received in revised form 7 July 2003; accepted 8 July 2003.

^* Corresponding author. Address: Department of Cardiac Surgery, Innsbruck University Hospital, Anichstrasse 35, A-6020 Innsbruck, Austria. Tel.: +43-512-504-3806; fax: +43-512-504-2528
e-mail: johannes.o.bonatti{at}uibk.ac.at

Objective: C-type natriuretic peptide (CNP), which is produced by vascular endothelial cells, exhibits anti-proliferative and anti-inflammatory effects. Cytotoxic T-lymphocytes may be involved in vein graft disease. Attenuation of vein graft disease necessitates a remodelling of the arterialized vein towards a more contractile phenotype which is characterized, among other factors, by the calponin amount. We investigated the effects of perivascularly applied CNP in a mouse model of vein graft disease. Methods: C57BL6J mice underwent interposition of the inferior vena cava from isogenic donor mice into the common carotid artery using a previously described cuff technique. In the treatment group, 10^-6 mol/l of CNP were applied locally in pluronic gel. The control group did not receive local treatment. Grafts were harvested at 1, 2, 4, and 8 weeks and underwent morphometric analysis as well as immunohistochemical analysis. Results: In grafted veins without treatment (controls) median intimal thickness was 10 (6–29), 12 (8–40) µm, was 47 (12–58), and 79 (62–146) µm after 1, 2, 4 and 8 weeks, respectively. In the treatment groups, which received 10^-6 mol/l of CNP, the intimal thickness was 5 (3–6), 6 (4–15), 32 (5–54), and 43 (39–70) µm after 1, 2, 4 and 8 weeks, respectively. This reduction of intimal thickness was significant at 1, 2 and 8 weeks. Immunohistochemically, the reduction of intimal thickness was associated with a decreased infiltration of CD-8 positive cells and an increased amount of calponin in the CNP-treated grafts. Conclusion: We conclude that perivascular application of CNP inhibits neointimal hyperplasia of vein grafts in a mouse model. These results suggest that CNP may have a therapeutic potential for the prevention of vein graft disease.

Key Words: Coronary artery bypass graft • Neointimal hyperplasia • C-type natriuretic peptide • Natriuretic peptide • Vein graft

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