Endothelial Progenitor Cell Biology and Vascular Recovery Following Transradial Cardiac Catheterization

Abstract

Background: Transradial catheterization is associated with radial artery injury and vasomotor dysfunction and represents an accessible model of acute vascular injury in humans. We characterized vascular injury and functional recovery to understand the role of circulating endothelial progenitor cells in vascular repair.

Methods and results: In 50 patients (aged 64±10 years, 70% male) undergoing transradial cardiac catheterization, radial artery injury was assessed by optical coherence tomography and examination of explanted vascular sheaths. Flow- and nitrate-mediated dilatation of the radial artery was assessed in both arms at baseline, at 24 hours, and at 1, 4, and 12 weeks. Circulating endothelial progenitor cell populations were quantified using flow cytometry. Late endothelial outgrowth colonies were isolated and examined in vitro. Optical coherence tomography identified macroscopic injury in 12 of 50 patients (24%), but endothelial cells (1.9±1.2×104 cells) were isolated from all arterial sheaths examined. Compared with the noncatheterized radial artery, flow-mediated vasodilatation was impaired in the catheterized artery at 24 hours (9.9±4.6% versus 4.1±3.1%, P<0.0001) and recovered by 12 weeks (8.1±4.9% versus 10.1±4.9%, P=0.09). Although the number of CD133+ cells increased 24 hours after catheterization (P=0.02), the numbers of CD34+ cells and endothelial outgrowth colonies were unchanged. Migration of endothelial cells derived from endothelial outgrowth colonies correlated with arterial function before catheterization but was not related to recovery of function following injury.

Conclusions: Transradial cardiac catheterization causes endothelial denudation, vascular injury, and vasomotor dysfunction that recover over 12 weeks. Recovery of vascular function does not appear to be dependent on the mobilization or function of endothelial progenitor cells.

Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02147119.

Keywords: cardiac catheterization; endothelial cell; endothelial function; radial artery catheter; vascular imaging.

© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Figures

Figure 1

Radial artery injury following cardiac catheterization. Macroscopic injury was detectable on intravascular imaging in 12 of 50 patients (20%). Healthy uninjured artery at sheath withdrawal (A). Small intimal tear at the 7 o'clock position (B). Extensive circumferential dissection extending into the media (C).

Figure 2

Changes in radial artery flow‐ and nitrate‐mediated dilatation after catheterization. Flow‐mediated dilatation in the catheterized radial artery was impaired at 24 h and at 1 and 4 wk compared with the noncatheterized radial artery but recovered by 3 months. Nitrate‐mediated dilatation was impaired at 24 h and 1 wk, but by 4 wk, there was no longer a significant difference between catheterized and noncatheterized radial arteries. Red lines represent the catheterized right radial artery, and blue lines represent the noncatheterized left radial artery. Mean and 95% confidence intervals are displayed. Vasomotion in the catheterized arm both in response to glyceryl trinitrate and flow‐mediated dilatation was reduced (ANOVA, P<0.05) Bonferroni post hoc tests were used to compare catheterized and uncatheterized arteries at different time points (*P<0.05 for catheterized vs noncatheterized comparison).

Figure 3

The effect of vascular injury on circulating progenitor cells. Patients were classified according to whether they sustained vascular injury. This was defined as having either macroscopic radial artery injury on optical coherence tomography (n=10), percutaneous coronary intervention (PCI; n=16), or both (n=2). Those in the no‐injury group had cardiac catheterization alone with no radial artery injury or PCI (n=20). There was no significant change in peripheral blood CD34+ cells at 24 hours after angiography in either group (A). There was a modest increase in CD 133+ cells at 24 hours after angiography that was significant in those with evidence of vascular injury but not in those without (B). There was no significant increase in CD34+ KDR + or CD34+ CD133+ KDR + cell concentration in either group (C). Values shown are median with interquartile range. The Wilcoxon matched pairs test was used for comparisons between baseline and 24 h.

Figure 4

Late‐outgrowth endothelial colony and wound healing analysis. Colonies of late‐outgrowth endothelial cells were isolated and characterized. Immunofluorescence for DAPI (diamidino‐2‐phenylindole; nuclei [blue]), CD31 (fluorescein isothiocyanate; green), and CD34 (Alexa 568; red) was performed. Cells had a comparable phenotype to vascular endothelial cells with ubiquitous expression of CD31 and CD34. Scale bars = 100 μm. A, Assessment of endothelial outgrowth cell migratory capacity was assessed using a “scratch” wound healing assay between 0 and 16 h (B). There was no significant difference in the number of endothelial outgrowth cell colonies isolated (C), their migratory potential (D), or cell‐surface marker profile (P>0.05 for all comparisons) (E) between colonies isolated at baseline and 24 h after angiography.