Effect of coacervated alpha-elastin on proliferation of vascular smooth muscle and endothelial cells.
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 developing a small-diameter prosthesis may be to stimulate endothelialization and thereby inhibit AIH. In this study, we investigated the effect of coacervated and crosslinked alpha-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, respectively. 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 alpha-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 alpha-elastin was coated and crosslinked. 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 alpha-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 alpha-elastin. These results suggest that coating and crosslinking a coacervated alpha-elastin into the structure of arterial prosthesis may inhibit AIH and stimulate endothelialization.
Ito
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Second Department of Surgery, Tokyo Medical College, Japan.
Ishimaru
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Wilson
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D017738:Alkanesulfonic Acids / Q000737:chemistry; D000704:Analysis of Variance; D000714:Anastomosis, Surgical / Q000009:adverse effects; D000818:Animals; D001011:Aorta; D001158:Arteries / Q000166:cytology / Q000293:injuries / Q000601:surgery; D001807:Blood Vessel Prosthesis; D002021:Buffers; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement; D002478:Cells, Cultured; D011232:Chemical Precipitation; D003432:Cross-Linking Reagents / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004549:Elastin / Q000008:administration & dosage / Q000737:chemistry / Q000187:drug effects / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006965:Hyperplasia; D009025:Morpholines / Q000737:chemistry; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D011126:Polypropylenes / Q000737:chemistry; D011474:Prosthesis Design; D011498:Protein Precursors / Q000737:chemistry / Q000187:drug effects; D019275:Radiopharmaceuticals; D013499:Surface Properties; D013552:Swine; D013936:Thymidine; D014316:Tritium; D017539:Tunica Intima / Q000166:cytology / Q000187:drug effects; D017540:Tunica Media / Q000166:cytology / Q000187:drug effects
D017738:Alkanesulfonic Acids; D002021:Buffers; D003432:Cross-Linking Reagents; D009025:Morpholines; D011126:Polypropylenes; D011498:Protein Precursors; D019275:Radiopharmaceuticals; C050906:polyglycerol polyglycidyl ether; D014316:Tritium; C004550:2-(N-morpholino)ethanesulfonic acid; C019058:proelastin; D004549:Elastin; D013936:Thymidine