Potentially positive ageing-related variations of medial smooth muscle cells in the saphenous veins used as aortocoronary bypass grafts

Abstract

Introduction. Currently, elderly people constitute a large proportion of patients undergoing coronary artery bypass grafting (CABG). Activated smooth muscle cells in the tunica media of saphenous vein (SV) grafts are thought to play a key role in the formation of neointima and development of occluding atherosclerotic plaques. The aim of this study was to identify ageing-related variations in the expression of the smooth muscle cells proteins that may impact on patency rate of the grafts and the CABG outcomes. Material and methods. The study involved 216 consecutive patients with the mean of 62.7 ± 8.4 years who underwent isolated CABG with at least one SV aortocoronary bypass graft. Expression of a-smooth muscle actin (a-SM actin), smooth muscle-myosin heavy chain (SM-MHC), calponin (CALP), cytokeratin 8 (CK-8), metalloproteinase-2 (MMP-2) and tissue inhibitors of metalloproteinases-2 and -3 (TIMP-2, TIMP-3) in the SV wall was assessed by immunohistochemistry and correlated with the age of patients. Results. Calponin and a-SM actin were expressed in all studied SV transplants. SM-MHC immunoreactivity was observed in SV segments in 68.5% of patients, whereas MMP-2a and TIMPs expression was found in 75% of cases. In more than 50% of analyzed SV transplants, no expression of cytokeratin-8 was found. Moderate correlations between preexisting expressions of either cytoskeletal or hemostatic proteins in the tunica media of the SV grafts and the age of CABG patients were demonstrated. They were positive for SM-MHC (r = 0.494), CALP (r = 0.548), TIMP-2 (r = 0.413) and TIMP-3 (r = 0.406) whereas negative for CK-8 (r = -0.528) and MMP-2 (r = -0.417). Conclusions. Age-dependent decreases in the expression of MMP-2 and CK-8 accompanied by increases in expression of SM-MHC, TIMP-2 and TIMP-3 may promote SV graft patency and, thus, suggest a rationale for common use of SV grafts in the elderly.

Characterisation of blood vessels used for coronary artery bypass surgery

“…Th ey also produce tissue inhibitors of metalloproteinases (TIMPs), and a balance between MMPs and TIMPs eventually determines the local homeostasis of the extracellular matrix [30]. In research by Perek et al (2016) evaluating the expression of proteins, the majority of saphenous vein segments exhibited weak or moderate immunostaining of MMP-2, TIMP-2 and TIMP-3 within the tunica media. Th e tissue expression of MMP-2 and TIMPs has been associated with the age of the patients [31].…”

“…In research by Perek et al (2016) evaluating the expression of proteins, the majority of saphenous vein segments exhibited weak or moderate immunostaining of MMP-2, TIMP-2 and TIMP-3 within the tunica media. Th e tissue expression of MMP-2 and TIMPs has been associated with the age of the patients [31]. Th e degradation of extracellular matrix by MMPs, which provides a structural framework essential for the functional properties of vessel wall, was found to be a prerequisite for smooth muscle cells migration, a critical step in neointima formation [27].…”

“…Moreover, baseline level of MMP-2 in the saphenous vein wall was shown to have a strong linear correlation with the degree of luminal narrowing at 1 year aft er coronary artery bypass graft [32]. Perek et al (2016) stated that saphenous vein segments may be more appropriate graft s in the elderly population. Moreover, their study also demonstrated increased tissue activity of TIMP-2 and TIMP-3 in the tunica media of the saphenous vein segments [31].…”

“…Perek et al (2016) stated that saphenous vein segments may be more appropriate graft s in the elderly population. Moreover, their study also demonstrated increased tissue activity of TIMP-2 and TIMP-3 in the tunica media of the saphenous vein segments [31]. However, no correlation between the age of the patient and TIMP-2 activity in the human aortic specimen had been demonstrated [33].…”

Does Age Affect the Short- and Long-Term Outcomes of Coronary Bypass Grafting?

“…Clinical evidence in evaluating the efficacy of arterial versus vein graft use in this age group is sparse 33 but there is promising physiologic evidence supporting the use of SV grafts in elderly patients. 34 Contrary to the assumption that increased vascular fragility would increase the risk of CABG complications, the Trial of Invasive versus Medical Therapy in the Elderly (TIME) investigators found that patients at or above the age of 75 years receiving CABG in addition to GDMT rather than GDMT alone had fewer MACCEs. 35 This surprising finding was confirmed by Graham et al who found that while octogenarians had a higher mortality rate than septuagenarians 4 years after CABG, the absolute risk difference between survival after GDMT with CABG versus GDMT alone was greater in octogenarians.…”