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

Abstract

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.

Ultrastructural variability of macrophages in the wall of selected aorto-coronary bypass grafts

“…The findings of this study should be treated as complementary one for the previous articles focused on degeneration of aorto-coronary grafts and published by the same research team [13,19,20]. There it was pointed that macrophages may play a crucial role in grafts disease eventually leading to their occlusions and clinically recurrence of CAD symptoms [13].…”

“…More researchers stress a crucial role of macrophages in pathogenesis of aorto-coronary grafts failure [17,18]. It was previously found that distribution of macrophages, defined as CD68+ cells, differed between vessels with favorable and poor long-term outcomes [19]. The vascular segments with relatively high representation of macrophages in the inner vascular layers were found to be more prone to development of preterm graft disease related to early CAD symptoms recurrence.…”

MMP13 Expression Is Increased Following Mutant α-Synuclein Exposure and Promotes Inflammatory Responses in Microglia

“…Similarly, the neurodegeneration observed in PD can be partially attributed to the dysregulation of cellular functions influenced by MMPs (Yanuck, 2019 ). For example, MMP1 and MMP13 increase the ability of human fibroblasts and dendritic cells to phagocytose, respectively (Perek et al, 2013 ; Rustenhoven et al, 2016 ; Hunter et al, 2018 ; Pelekanou et al, 2018 ; Yoon et al, 2020 ). In neurodegenerative disorders, microglial expression of MMP13 is upregulated in response to amyloid beta (Ito et al, 2007 ) and knockdown of MMP13 in APP/PS1E9 mice rescued learning and memory deficits (Zhu et al, 2019 ).…”