Format

Send to

Choose Destination
See comment in PubMed Commons below
Int J Cardiol. 2014 Jul 1;174(3):688-95. doi: 10.1016/j.ijcard.2014.04.228. Epub 2014 Apr 25.

Polymeric stent materials dysregulate macrophage and endothelial cell functions: implications for coronary artery stent.

Author information

1
Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, United States.
2
Department of Maxillofacial Biomedical Engineering, Kyung Hee University, Seoul, South Korea.
3
Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, United States; Department of Maxillofacial Biomedical Engineering, Kyung Hee University, Seoul, South Korea. Electronic address: hak-joon.sung@vanderbilt.edu.

Abstract

BACKGROUND:

Biodegradable polymers have been applied as bulk or coating materials for coronary artery stents. The degradation of polymers, however, could induce endothelial dysfunction and aggravate neointimal formation. Here we use polymeric microparticles to simulate and demonstrate the effects of degraded stent materials on phagocytic activity, cell death and dysfunction of macrophages and endothelial cells.

METHODS:

Microparticles made of low molecular weight polyesters were incubated with human macrophages and coronary artery endothelial cells (ECs). Microparticle-induced phagocytosis, cytotoxicity, apoptosis, cytokine release and surface marker expression were determined by immunostaining or ELISA. Elastase expression was analyzed by ELISA and the elastase-mediated polymer degradation was assessed by mass spectrometry.

RESULTS:

We demonstrated that poly(D,L-lactic acid) (PLLA) and polycaprolactone (PCL) microparticles induced cytotoxicity in macrophages and ECs, partially through cell apoptosis. The particle treatment alleviated EC phagocytosis, as opposed to macrophages, but enhanced the expression of vascular cell adhesion molecule (VCAM)-1 along with decreased nitric oxide production, indicating that ECs were activated and lost their capacity to maintain homeostasis. The activation of both cell types induced the release of elastase or elastase-like protease, which further accelerated polymer degradation.

CONCLUSIONS:

This study revealed that low molecule weight PLLA and PCL microparticles increased cytotoxicity and dysregulated endothelial cell function, which in turn enhanced elastase release and polymer degradation. These indicate that polymer or polymer-coated stents impose a risk of endothelial dysfunction after deployment which can potentially lead to delayed endothelialization, neointimal hyperplasia and late thrombosis.

KEYWORDS:

Dysfunction; Elastase; Endothelial cell; Poly(L-lactic acid); Polycaprolactone; Stent

PMID:
24820736
PMCID:
PMC4070878
DOI:
10.1016/j.ijcard.2014.04.228
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center