Graft failure occurs in a sizeable proportion of coronary artery bypass conduits. We herein review relevant current evidence to give an overview of the incidence, pathophysiology, and clinical consequences of this multifactorial phenomenon. Thrombosis, endothelial dysfunction, vasospasm, and oxidative stress are different mechanisms associated with graft failure. Intrinsic morphological and functional features of the bypass conduits play a role in determining failure. Similarly, characteristics of the target coronary vessel, such as the severity of stenosis, the diameter, the extent of atherosclerotic burden, and previous endovascular interventions, are important determinants of graft outcome and must be taken into consideration at the time of surgery. Technical factors, such as the method used to harvest the conduits, the vasodilatory protocol, the storage solution, and the anastomotic technique, also play a major role in determining graft success. Furthermore, systemic atherosclerotic risk factors, such as age, sex, diabetes mellitus, hypertension, and dyslipidemia, have been variably associated with graft failure. The failure of a coronary graft is not always correlated with adverse clinical events, which vary according to the type, location, and reason for failed graft. Intraoperative flow verification and secondary prevention using antiplatelet and lipid-lowering agents can help reducing the incidence of graft failure.

Increased peak wall stress correlates with change in VSMC towards a synthetic phenotype mediated by ROS accumulation via CTGF. Understanding the molecular mechanisms that regulate VSMC towards a synthetic phenotype could unveil new regulatory pathways of aortic homoeostasis and impact the risk-stratification tool for patients at risk of aortic dissection and rupture.

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Objective Accumulation of reactive oxygen species (ROS) and remodeling of the microstructure of the cusp characterize aortic valve sclerosis, the early phase of calcific aortic valve disease. These events are associated with activation of valvular interstitial cells (VICs) toward an osteogenic-like phenotype. Because ROS cause DNA damage and transcriptional activation we investigated the relationship between ROS, DNA damage response, and transdifferentiation of VICs. Methods and Results Human aortic valve cusps and patient-matched VICs were collected from 39 patients both with and without calcific aortic valve disease. VICs were exposed to hydrogen peroxide (0.1–1 mmol/L) after cell transduction with extracellular superoxide dismutase/catalase adenoviruses and characterized for DNA-damage response, osteogenic transdifferentiation, and calcification. ROS induce relocalization of phosphorylated γH2AX, MRE11, and XRCC1 proteins with expression of osteogenic signaling molecule RUNX2 via AKT. We report a sustained activation of γH2AX in aortic valve sclerosis-derived VICs suggesting their impaired ability to repair DNA damage. Adenovirus superoxide dismutase/catalase transduction decreases ROS-induced DNA damage and VIC transdifferentiation in aortic valve sclerosis-derived cells. Finally, adenoviral transduction with catalase reverts ROS-mediated calcification and cellular transdifferentiation. Conclusion We conclude that the ROS-induced DNA damage response is dysfunctional in early asymptomatic stages of calcific aortic valve disease. We unveiled an association among ROS, DNA-damage response, and cellular transdifferentiation, reversible by antioxidant enzymes delivery.