Abstract 11102: Subendothelial Pericytes in the Human Arterial and Venous Vessel Intima are Causally Involved in Thromboembolic and Atherosclerotic/Proliferative Processes in Bypass Grafts with Lesioned Endothelium

Abstract

Introduction: The prognosis of bypass grafts, particularly those of venous origin, is unsatisfactory due to the occurrence of acute thromboembolic occlusion or atherosclerosis-like processes in the longer term. The pathogenetically relevant mechanisms in the intima have not been fully elucidated.

Hypothesis: Endothelial lesions of vascular grafts exposing intimal pericytes (P), trigger procoagulatory and proliferative processes. P may play a pathogenetically decisive role in the venous and arterial intima, which was not noticed before.

Methods: Immunohistochemical studies on remnants of bypass grafts of arterial and venous origin after their gentle explantation; cell isolation and tissue culture techniques; graft storage in a plasma derivative or in conventional preservation solutions; hemostasiological assays.

Results: In all venous and arterial vessel segments studied, a network of P exists directly beneath the endothelium. On their surface P express a high tissue factor concentration and are able to form the prothrombinase complex (formation of 7.8±1.3 pmol X_a or 0.34nmol ± 0.06 II_a in aortic, and 36.4±1.4 pmol X_a or 8.6nmol ± 1.1 II_a •min^-1•10^-6cells in venous intima, respectively), thus catalysing rapid accumulation of fibrin thrombi. Following endothelial lesions, and hence exposure to locally formed serum, P proliferate rapidly (doubling time 18 h). Preparation of bypass grafts using routine methods and crystalline solutions (saline, HTK solution) causes extensive endothelial denudation (>50%) particularly in venous grafts, thus exposing the firmly anchored, prothrombogenic intimal P. In contrast, sealing bypass grafts using a custom-built injector system to limit pressure (<200 mmHg) and subsequent storage in a plasma derivative preserves intimal structure (>90%) with retention of typical anti-thrombogenic endothelial activities.

Discussion: Exposed P play a key role in the pathogenesis of atherosclerotic processes particularly in venous grafts resulting in restenosis. The improved intraoperative handling techniques described above can improve graft prognosis considerably. Given their presence in the arterial intima, P may also play a hitherto unrecognized role in atherosclerosis in general.