Abstract
Saphenous vein graft disease is a timely problem in coronary artery bypass grafting. Indeed, after exposure of the vein to arterial blood flow, a progressive modification in the wall begins, due to proliferation of smooth muscle cells in the intima. As a consequence, the graft progressively occludes and this leads to recurrent ischemia. In the present study we employed a novel ex vivo culture system to assess the biological effects of arterial-like pressure on the human saphenous vein structure and physiology, and to compare the results to those achieved in the presence of a constant low pressure and flow mimicking the physiologic vein perfusion. While under both conditions we found an activation of Matrix Metallo-Proteases 2/9 and of microRNAs-21/146a/221, a specific effect of the arterial-like pressure was observed. This consisted in a marked geometrical remodeling, in the suppression of Tissue Inhibitor of Metallo-Protease-1, in the enhanced expression of TGF-β1 and BMP-2 mRNAs and, finally, in the upregulation of microRNAs-138/200b/200c. In addition, the veins exposed to arterial-like pressure showed an increase in the density of the adventitial vasa vasorum and of cells co-expressing NG2, CD44 and SM22α markers in the adventitia. Cells with nuclear expression of Sox-10, a transcription factor characterizing multipotent vascular stem cells, were finally found in adventitial vessels. Our findings suggest, for the first time, a role of arterial-like wall strain in the activation of pro-pathologic pathways resulting in adventitial vessels growth, activation of vasa vasorum cells, and upregulation of specific gene products associated to vascular remodeling and inflammation.
Highlights
Coronary artery bypass grafting (CABG) is a surgical procedure routinely used to re-vascularize the chronically ischemic myocardium since ‘60s [1]
This (S1 Video), consisted in a circumferential strain applied to the saphenous vein (SV) wall, and in particular to the luminal endothelial cells (ECs) and the medial smooth muscle cells (SMCs)
Results of experiments performed under the arterial-like condition or under the venous perfusion regimen were pairwise compared with results obtained in non-stimulated vessels
Summary
Coronary artery bypass grafting (CABG) is a surgical procedure routinely used to re-vascularize the chronically ischemic myocardium since ‘60s [1]. While vascular conduits derived from arterial sources such as the inner mammary or the radial arteries are preferred for their lower propensity to stenosis [4], the employment of the SV is unavoidable, especially in cases of ‘multi-vessel’ pathology[5] In these instances, even if “no touch” SV harvesting modalities preserving the vascular integrity have been introduced [4], there is still a high incidence of venous bypass failure. Vein bypass stenosis is caused by an overgrowth of smooth muscle cells (SMCs) These cells, switching from a contractile to a migratory/secretory phenotype [3,6], invade the intima and narrow the vessel lumen. Activation and recruitment of vein-resident cells with mesenchymal progenitor characteristics has been hypothesized [7,8,9,10]
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