Table 2. Three Clinical Stages of Vein Graft Healing.

Clinical stages	Time frame	Ultrastructural correlates	Molecular correlates
Lumen dilation and increased wall thickness	0-30 days	Endothelial denudation, medial wall edema, Cellular homing/ trafficking Apoptosis/necrosis Proliferation Matrix remodeling	Inducers: (DAMPS, neo-antigens, ROS serum growth factors) Amplifiers: (TNF-α, IL-1) Receptors: TLRs, NLRs, IL-1R, and TNF-αR 1,-2 Transducers: (AP-1, NFκB, NFAT)
Stiffness increase in Young's elastic modulus.	3-6 months	Myofibrobast transformation, Collagen deposition	Fibrosis (TGF-β, CTGF, SMAD 1/2, TGFR1, TGFR2) Cross linking ECM transglutaminases (factor XIIIa)
Endothelial recovery, vein graft exhibits flow mediated vasodilation	> 6 months	Complete endothelial coverage, barrier function, and return of vasoreactivity	EDRF: eNOS, NO, prostacyclin, EDHF

Innate immune inducers: DAMPS damage associated molecular patterns, ROS reactive oxygen species. Amplifiers: TNF tumor necrosis factor, IL-1 interleukin-1. Receptors: TLR toll like receptor, NLR nod like receptor. Transducers: AP-1 activated protein-1, NFκB nuclear factor kappa B, NFAT nuclear factor of activated T cells. Fibrosis: TGF-β transforming growth factor-β, CTGF connective tissue growth factor, SMAD mothers against decapentaplegic homologue, TGFR transforming growth factor-β receptor. EDRF endothelium derived relaxing factors, eNOS endothelium nitric oxide synthase, NO nitric oxide, EDHF endothelium derived hyperpolarizing factor