Cytokeratin 8 in venous grafts: A factor of unfavorable long-term prognosis in coronary artery bypass grafting patients

Perek, Bartłomiej; Malińska, Agnieszka; Ostalska‐Nowicka, Danuta; Puślecki, Mateusz; Ligowski, Marcin; Misterski, Marcin; Zabel, Maciej; Jemielity, Marek; Nowicki, Michał

doi:10.5603/cj.2013.0142

Cited by 11 publications

(10 citation statements)

References 28 publications

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“…As mentioned before, neointima formation is a result of many active processes and any form of preexisting degeneration or impaired ability of SMCs to react to different local and systemic stimuli may be considered as protective [22]. This finding supports, at least partially, a marked decrease in rate of post-discharge SV graft failure in the elderly, defined as 70 years or older [14,23].…”

Section: Discussionsupporting

confidence: 73%

“…Interestingly, SMCs obtained from varicose veins showed significantly higher rate of cell proliferation and migration and presented a 20% reduction in the expression of SM-MHC compared with the SMCs derived from normal veins [13]. Contrary to the aforementioned proteins, cytokeration-8, a marker of immature and fetal cells, found in our previous study as an independent risk factor for premature occlusion of SV grafts [14], in our study showed adverse correlation with age. Thus, preexisting variable tissue expression of marker cytoskeletal SMCs proteins within the tunica media of SV graft may suggest that younger SV grafts recipients may be at higher risk of premature venous graft failure.…”

Section: Discussioncontrasting

confidence: 51%

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

Perek

Malińska

Gąsowski

et al. 2015

Folia Histochem Cytobiol.

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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.

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Section: Discussionsupporting

confidence: 73%

Section: Discussioncontrasting

confidence: 51%

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

Perek

Malińska

Gąsowski

et al. 2015

Folia Histochem Cytobiol.

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“…However, it is unlikely that non-diabetic patients without clinical progression of CAD had significant stenosis or occlusions in aortocoronary grafts. Such findings were previously reported by our team [12,25]. Favourable long-term outcomes of arterial grafts, particularly the ITA, make it difficult to define the predictors of premature graft disease and failure.…”

Section: Gelatinase Expression In Aortocoronary Graft Wallssupporting

confidence: 78%

Variability in gelatinase expression in the walls of vessels used as aortocoronary conduits may impact long-term graft patency

et al. 2019

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Background: An imbalance between the activity of matrix metalloproteinases (MMPs), particularly gelatinases, and tissue inhibitors of metalloproteinases (TIMPs) is considered as one of the mechanisms leading to aortocoronary graft failure. Aim: We aimed to assess the variability in gelatinase expression in the walls of aortocoronary conduits and to evaluate its impact on coronary artery bypass grafting (CABG) outcomes. Methods: The study included 101 consecutive patients (61 men and 40 women) who underwent CABG. An immunohistochemical analysis of MMP-2, MMP-9, TIMP-1, and TIMP-2 expression was performed on the cross-sections of the internal thoracic artery (ITA), radial artery (RA), and saphenous vein (SV). The histological findings were compared between patients with SV graft disease (SVGD[+] group) and those without occlusions in the SV (SVGD[-] group). Results: The median MMP and TIMP expression was the weakest in the ITA wall. MMP expression was comparable between the RA and SV cross-sections, whereas TIMP expression was stronger in the RA than in the SV wall (p < 0.05). In most SV segments, but not in the arteries, immunostaining intensity for MMP was comparable to or stronger than for TIMPs. In the veins harvested from the SVGD(+) group, MMP-2 and MMP-9 tissue expression was more pronounced than in the SVGD(-) group. TIMP levels were comparable between groups. Conclusions: Imbalance in the metalloproteinase-to-inhibitor tissue expression in the vessel wall might predispose to graft failure. A stronger expression of TIMPs than MMPs in the arterial grafts might explain favourable long-term outcomes.

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“…While the Remmele scale applied improves quality of the analysis, experience of research remains mandatory. Histologists involved in this project may legitimate their expertise with many previous peer-reviewed publications [22,24].…”

Section: Limitations Of the Studymentioning

confidence: 99%

Infiltration of CD68+ cells correlates positively with matrix metalloproteinase 2 expression in the arteries used as aortocoronary bypass grafts. Possible clinical implications

et al. 2020

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Background: Late failure of arterial aortocoronary conduits may result from abnormal activity of cells found in the vessel wall, including macrophages. The purpose of this study was to assess if there are any associations between the number of macrophages and overexpression of matrix metalloproteinases (MMPs) in the wall of arterial grafts, as well as their clinical significance. Methods: This study involved 128 consecutive patients with a mean age of 64.9 ± 9.7 years who underwent elective surgery for coronary artery disease (CAD). The surplus segments of internal thoracic artery (ITA) and radial arteries (RA) were taken for immunohistochemical analysis of macrophage numbers and MMPs expression. The participants who reached the clinical primary end-point (cardiacrelated death, acute coronary syndrome or progression of CAD) had a follow-up angiography. Results: The mean numbers of macrophages were higher on RA (70 [24; 112]) than ITA cross-sections (44 [24; 59]; p < 0.001). Median expression of both MMP2 and MMP9 were stronger in the ITA than RA cross-sections (p < 0.001). A significant positive correlation of MMP2 expression and a number of macrophages infiltrating the tunica media of arterial segments were noted on both ITA and RA crosssections. In addition, the arterial segments of the 6 patients who reached clinical end-point had higher numbers of macrophages and stronger MMP2 expression when compared to the rest of the participants. Conclusions: Macrophage infiltration of arterial wall grafts prior to harvesting may be associated with higher risk of late occlusion and MMP 2 might be facilitating this process.

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Cytokeratin 8 in venous grafts: A factor of unfavorable long-term prognosis in coronary artery bypass grafting patients

Abstract: (Cardiol J 2013; 20, 6: 583-591)

Cited by 11 publications

References 28 publications

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

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

Variability in gelatinase expression in the walls of vessels used as aortocoronary conduits may impact long-term graft patency

Infiltration of CD68+ cells correlates positively with matrix metalloproteinase 2 expression in the arteries used as aortocoronary bypass grafts. Possible clinical implications

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