Time course of VCAM-1 expression in reperfused myocardial infarction in swine and its relation to retention of intracoronary administered bone marrow-derived mononuclear cells

Abstract

BackgroundIntracoronary infusion of autologous bone marrow-derived mononuclear cells (BMMNC), after acute myocardial infarction (AMI), has been shown to improve myocardial function. However, therapeutic efficacy is limited, possibly because cell retention rates are low, suggesting that optimization of cell retention might increase therapeutic efficacy. Since retention of injected BMMNC is observed only within infarcted, but not remote, myocardium, we hypothesized that adhesion molecules on activated endothelium following reperfusion are essential. Consequently, we investigated the role of vascular cell adhesion molecule 1 (VCAM-1) in BMMNC retention in swine undergoing reperfused AMI produced by 120 min of percutaneous left circumflex coronary occlusion.Methods and resultsVCAM-1 expression in the infarct and remote region was quantified at 1, 3, 7, 14, and 35 days, post-reperfusion (n≥6 swine per group). Since expression levels were significantly higher at 3 days (2.41±0.62%) than at 7 days (0.98±0.28%; p<0.05), we compared the degree of cell retention at those time points in a follow-up study, in which an average of 43·106 autologous BMMNCs were infused intracoronary at 3, or 7 days, post-reperfusion (n = 6 swine per group) and retention was histologically quantified one hour after intracoronary infusion of autologous BMMNCs. Although VCAM-1 expression correlated with retention of BMMNC within each time point, overall BMMNC retention was similar at day 3 and day 7 (2.3±1.3% vs. 3.1±1.4%, p = 0.72). This was not due to the composition of infused bone marrow cell fractions (analyzed with flow cytometry; n = 5 per group), as cell composition of the infused BMMNC fractions was similar.ConclusionThese findings suggest that VCAM-1 expression influences to a small degree, but is not the principal determinant of, BMMNC retention.

Kinetics and prognostic value of soluble VCAM‐1 in ST‐segment elevation myocardial infarction patients

“…Furthermore, the time course of VCAM-1 release was evaluated by Uitterdijk et al on swine. 27 They reported a significant increase in sVCAM-1 expression during the first week after MI followed by a decrease up Here, we demonstrated that sVCAM-1 is an early biomarker of severity after STEMI and is correlated with IS, LVEF, and LV remodeling. sVCAM-1 appeared as an efficient predictor of negative clinical outcome as illustrated by the ROC curve, superior to a classic marker of IS such as creatine kinase.…”

“…Mulvihill et al 26 found a sustained sVCAM‐1 increase up to 6 months following an ACS. Furthermore, the time course of VCAM‐1 release was evaluated by Uitterdijk et al on swine 27 . They reported a significant increase in sVCAM‐1 expression during the first week after MI followed by a decrease up to 1 month.…”

Integrin α4 Positive Subpopulation in Adipose Derived Stem Cells Effectively Reduces Infarct Size through Enhanced Engraftment into Myocardial Infarction

“…We demonstrated that the integrin α 4 + ASCs subpopulation highly expressed integrin α 4 on their surface, and their binding partner of VCAM-1 was up-regulated in the infarcted myocardium. VCAM-1 expression peaked at 3 days post-MI and recovered to normalization 14 days post-MI ( 16 ). VCAM-1 expression correlated well with the extent of bone marrow (BM)-MSCs retention at 3 days and 7 days post-MI ( 16 ).…”

Modification of human MSC surface with oligopeptide‐PEG‐lipids for selective binding to activated endothelium

“…35 However, there are a number of target receptors expressed on the cell surface under ischemia: for examples, some cell adhesion molecules including VCAM-1, ICAM-1 are highly expressed. 36 Since the level and timing of the expression are different among those receptors during the ischemia, it is unclear that which receptors should be the responsible target for MSC delivery. For example, the E-selectin expression level reached the plateau at around 12 h after occlusion.…”