title: Heparin coating of small-caliber decellularized xenografts reduces macrophage infiltration and intimal hyperplasia.
abstract: Small-caliber decellularized xenografts with surface heparin coating are known to reduce in vivo thrombogenicity. This study was performed to examine whether heparin coating on the small-caliber decellularized xenografts would reduce macrophage infiltration and intimal hyperplasia. In a rabbit model of bilateral carotid implantation, each of the animals (n = 18) received a heparin-coated decellularized xenograft from a canine carotid artery on one side and a nonheparin-coated one on the other side. These experiments were terminated respectively at 1 week (n = 6), 3 weeks (n = 6), and 12 weeks (n = 6). Results showed that, compared with the nonheparin-coated grafts, the heparin-coated grafts had significantly less macrophage infiltration 1 week after implantation, identified by the mouse antirabbit macrophage antibody (RAM11)-positive cells on the vascular wall, covering all the proximal, middle, and distal parts of the grafts (P < 0.01). Moreover, the heparin-coated grafts also showed less deposition of proliferation cell nuclear antigen (PCNA)-positive cells on the vascular wall, indicating less cell proliferation, which was significant not only at 1 week (P < 0.01) but also at 12 weeks (P < 0.01). Intimal hyperplasia, measured by the intimal : media (I : M) ratio, was found similar in both groups at 1 and 3 weeks. However, the I : M ratio was significantly lower in the heparin-coated group than in the nonheparin-coated group at 12 weeks, especially in the proximal anastomosis area (0.76 +/- 0.12 vs. 0.345 +/- 0.06, P < 0.01). Heparin coating of small-caliber decellularized xenografts is associated with an early reduction of macrophage infiltration and intimal hyperplasia in a rabbit model of bilateral carotid artery implantation for 12 weeks. Thus, heparin coating appears to deliver not only the antithrombogeneity but also the antiproliferative property for small-caliber decellularized xenografts.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Renji Hospital, Shanghai Jiaotong University Medical School, Shanghai, China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Cai
authors.forename: Y John
authors.initials: YJ
authors.lastname: Gu
authors.forename: Xue-Ning
authors.initials: XN
authors.lastname: Wang
authors.forename: Chang-Zhi
authors.initials: CZ
authors.lastname: Chen
mesh_terms: D000818:Animals; D019917:Blood Vessel Prosthesis Implantation; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006493:Heparin / Q000737:chemistry / Q000494:pharmacology*; D006965:Hyperplasia; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D008297:Male; D011817:Rabbits; D014183:Transplantation, Heterologous / Q000379:methods*; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology*
chemical_list: D006493:Heparin