Effect of Coacervated α-Elastin on Proliferation of Vascular Smooth Muscle and Endothelial Cells

Author:

Ito Shigeki1,Ishimaru Shin1,Wilson Samuel E.2

Affiliation:

1. Second Department of Surgery, Tokyo Medical College, Tokyo, Japan.

2. Department of Surgery, University of California, Irvine, California.

Abstract

The arterial wall injury associated with arterial graft implantation causes smooth muscle cells (SMCs) in the media to migrate and proliferate in the intima at the graft-artery junction resulting in anastomotic intimal hyperplasia (AIH). An important step in devel oping a small-diameter prosthesis may be to stimulate endothelialization and thereby inhibit AIH. In this study, we investigated the effect of coacervated and crosslinked α-elastin on proliferation of SMCs and endothelial cells (ECs) in vitro. Coacervation is an important step in the conversion of proelastin to make an elastin fiber in vivo. SMCs and ECs were prepared from porcine aortic media and endothelium, respec tively. SMCs and ECs (three to five passages, 4 x 10 4 cells/well) were seeded onto 12 well plates, coated and crosslinked with 0 or 10 mg/mL of coacervated α-elastin. After the 1st, 2nd, or 3rd day of cultivation, proliferation was assayed by scintillation counting of [3H]-thymidine incorporation. For the 4th day only, 0, 0.1, 1, 10 mg/mL concentration of coacervated α-elastin was coated and crosslinked. (continued on next page) SMC proliferation (1st, 2nd day: p<0.005; 3rd, 4th day: p<0.0001) was significantly inhibited over time and dose dependently, eg, 0.1 mg/mL (45.7 ±2.3%: % of control p<0.005), 1 mg/mL (5.9 ±0.7%, p<0.0005), 10 mg/mL (2.8 ±0.4%, p<0.0005). EC proliferation was inhibited over time by 10 mg/mL of coacervated α-elastin (2nd, 3rd day: p<0.005; 4th day: p<0.0001), but proliferation (132.8 ±9.9%: % of control p=NS) was stimulated by 0.1 mg/mL of coacervated α-elastin. These results suggest that coating and crosslinking a coacervated α-elastin into the structure of arterial prosthesis may inhibit AIH and stimulate endothelialization.

Publisher

SAGE Publications

Subject

Cardiology and Cardiovascular Medicine

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