Perivascular Adipose Tissue Is a Major Source of Nitric Oxide in Saphenous Vein Grafts Harvested via the No‐Touch Technique

Abstract

Background Saphenous vein grafts (SVGs) are broadly used in coronary artery bypass grafting despite their inferior patency compared with arterial grafts. Recently, the no‐touch technique (NT), in which an SVG is harvested with a pedicle of perivascular adipose tissue (PVAT) without conduit distension, was shown to improve long‐term patency compared with conventional preparation (CV), wherein outer tissue is removed with distension. The NT was also reportedly associated with reduced atherosclerosis. Although endothelial damage provoked by conventional distension may underlie poor patency when CV is performed, the precise mechanisms underlying the salutary effects of the NT have been unclear. Methods and Results Residual SVGs prepared with CV (CV‐SVGs) or NT (NT‐SVGs) were obtained during coronary artery bypass grafting. Nitric oxide (NO 2 − /NO 3 − (NO x )) levels after 24 hours of tissue culture were quantified. The protein expression and localization were analyzed. The isometric force of SVG strips was measured. NT‐SVGs showed superior NO x production to CV‐SVGs. PVAT generated the majority of NO x in NT‐SVGs. PVAT highly expressed arginosuccinate synthase 1, a rate‐limiting enzyme in the molecular circuit for NO synthesis, thereby continuously providing the substrate for NO. A substantial level of endothelial NO synthase was also expressed in PVAT. Pharmacological inhibition of arginosuccinate synthase 1 or endothelial NO synthase significantly suppressed the NO x production in NT‐SVGs. PVAT induced vasorelaxation through NO production, even in the endothelium‐denuded SVG strips. Conclusions Preserving PVAT was predominantly involved in the superior NO x production in NT‐SVGs. Since NO plays crucial roles in suppressing atherosclerosis, this mechanism may greatly contribute to the excellent patency in NT‐SVGs.