Vein graft thrombi, a niche for smooth muscle cell colonization – a hypothesis to explain the asymmetry of intimal hyperplasia

Abstract

EssentialsVein graft failure is the most frequent late onset complication of coronary artery bypass grafting. Cuff technique-based interposition mouse model including new anticoagulation regime was conducted. Early vein graft thrombi may serve as a niche for smooth muscle cell colonization. The focal character of early thrombi may form the basis for the asymmetry of intimal hyperplasia.Summary. Background: Autologous saphenous veins are widely used in coronary artery bypass grafting; however, 10 years after surgery, 40% of grafts are completely occluded, and another 30% show reduced blood flow. Objective: In the past, the central processes and signaling pathways responsible for this loss of patency have been identified. However, one central finding in the process of graft failure is so far not understood: the asymmetric character of intimal hyperplasia. It was the goal of the present study to address this aspect. Methods: By the use of a cuff technique-based vein interposition mouse model with a new anticoagulation regime, alterations in vein grafts were analyzed 1 h, 1 day, 2 days, 3 days, 7 days and 21 days after reperfusion by means of immunolabeling, histochemistry, and high-resolution ultrasound. Results: The novel and major finding of this study is that the vein graft thrombus may serve as a niche that is infiltrated and colonized by smooth muscle cells (SMCs). Fibroblast growth factor-1 and platelet-derived growth factor-B may be the SMCattracting factors in the thrombus. The focal character of early thrombi may define the focal and asymmetric character of vein graft intimal hyperplasia. Conclusions: Inhibiting the formation and reducing the size of early thrombi is an old concept for reducing vein graft failure. However, in light of the present new findings obtained under a cliniclike anticoagulation regime, early vein graft thrombus prevention/size reduction should be revisited in the prevention of graft failure.

Toward endothelialization via vascular endothelial growth factor immobilization on cell‐repelling functional polyurethanes

“…Our findings are consistent with previous studies showing high selectivity of ECs over SMCs on VEGF‐bound surfaces [Figures (C) and (A)]. It has been reported that overgrowth of SMCs on vascular lumen can cause intimal hyperplasia, which, together with luminal thrombogenesis, is responsible for the failure of small diameter vascular grafts. Resistance of SMCs from the vascular lumen is therefore as important as the capture of ECs onto the lumen.…”

Early Natural History of Neotissue Formation in Tissue-Engineered Vascular Grafts in a Murine Model

“…Only two samples had a high density of SMCs in the luminal neotissue, one each at days 5 and 7. However, the 5-day sample had visible RBCs and vWF + regions, indicative of platelets, suggesting that the SMCs might simply have invaded an existing thrombus [26]. Although we did not find strong evidence supporting intimal hyperplasia-driving stenosis in the absence of thrombosis, it is unknown as to whether SMC proliferation and ECM production would contribute to additional narrowing if this sample had not been explanted.…”

“…These processes are not necessarily distinct but may be different interpretations of the same phenomenon. Remodeling of thrombi has been attributed to intimal hyperplasia and similarly, thrombosis has been hypothesized to be the stimulus for intimal hyperplasia [6,26,30,31]. Therefore, in the absence of direct evidence of thrombosis, stenosis first recognized at 2 weeks or beyond has largely been attributed to hyperplasia and/or overproduction of ECM.…”

Improving in vivo outcomes of decellularized vascular grafts via incorporation of a novel extracellular matrix

“…A recent study has shown that early vein graft thrombi may serve as a niche for the establishment of SMCs in the media due to the rich pool of chemoattractants found there. Such niches may result in the thicker regions of SMC growth, and thus the occurrence of asymmetrical neointima [50]. Therefore, it is possible that the symmetry found in the TSP2 KO ECM modified grafts is a further indication that a non-thrombogenic surface is maintained in the early stages of implantation until endothelialization can occur.…”