The modulation of smooth muscle cell phenotype is an early event in human aorto-coronary saphenous vein grafts

Abstract

The morphological changes in human vein grafts occurring in the first days after a coronary bypass operation (CBP) are rarely reported in the literature. Sections of aorto-coronary vein grafts from 11 patients who died during the first 10 days after a CBP were obtained at autopsy. The number of vein grafts per patient ranged from 1 to 4, yielding a total of 28 vein grafts. The early changes in the vein grafts have been studied by light microscopy, immunohistochemistry, transmission and scanning electron microscopy. The study demonstrates that soon after grafting, the vein wall is infiltrated by polymorphonuclear leucocytes (PMN). At 24 h the endothelium shows extensive desquamation. The massive migration of PMN through the venous wall occurs simultaneously with the endothelial damage. The circular layer of the media is severely damaged, resulting in a loss of smooth muscle cells (SMC). The remaining SMC in this layer show a change toward the synthetic phenotype and a reduced expression of alpha-smooth muscle actin. These early changes in the SMC function may initiate the process of fibrosis in the intima and the media of the vein grafts.

Mouse Model of Venous Bypass Graft Arteriosclerosis

“…Interestingly, significant cell loss and vessel wall degeneration in the vein graft was observed 1 week after implantation simultaneous to connective tissue deposition and mononuclear cell infiltration in adventitia ( Figure 2B). Concordant with these observations is a report that a loss of endothelial and smooth muscle cells in human saphenous vein bypass grafts was demonstrated 1 to 10 days postoperatively, 24 suggesting that changes in the early stage of grafts in this mouse model are similar to those in humans. By 2 weeks, mononuclear cells infiltrated into the vessel wall from both lumen and adventitia sides ( Figure 2C).…”

“…25,26 First, a marked loss of smooth muscle cells has been observed in lesions in the early stage of vein grafts of humans and mice (Ref. 24; Figure 2B). Secondly, the human lesions have an inflammatory nature characterized by mononuclear cell infiltration in the early stage of vein bypass grafts, and the lesions seen in our mouse models contain abundant MAC-1 ϩ monocytes/macrophages (Ref.…”

Impaired arterial neointima formation in mice with disruption of the plasminogen gene.

“…Wound healing and the associated arterial neointima formation and reendothelialization initiated at the uninjured borders with subsequent progression into the necrotic center. This healing process is similar to that observed after venous grafts (45,46), laser-induced thermal injury (47), necrotizing transluminal ligation injury (48), and end-to-end microvascular anastomosis (49).…”

Oxidative Stress and Lipid Retention in Vascular Grafts

“…They include pulsatile stretch and medial injury sustained by SVGs. [22][23][24][25] In fact, focal vascular trauma has been shown to upregulate ⅐O 2 Ϫ in the arterial system, 26,27 although studies of vascular grafts have been limited. 28 Numerous growth factors released at the site of tissue injury, including thrombin, are known to increase NAD(P)H oxidase activity.…”