BACKGROUND: Vein graft disease limits the late results of coronary revascularization. C-type natriuretic peptide (CNP) inhibits the growth of vascular smooth muscle cells. Given the effects of CNP on cGMP cascade, we hypothesized that transfected CNP genes modulate endothelial repair and thrombogenicity in the vein graft. METHODS AND RESULTS: Autologous rabbit jugular vein grafts were incubated ex vivo in a solution of adenovirus vectors containing CNP gene (Ad.CNP) or Escherichia coli lac Z gene (Ad.LacZ) and then interposed in the carotid artery. Reendothelialization, mural thrombi formation, and intima/media ratio were evaluated on the 14th and 28th postoperative days. More reendothelialization was seen in Ad.CNP-infected grafts than in Ad.LacZ-infected grafts both at 14 days (0.81+/-0.05 versus 0.30+/-0.14, P<0.01) and at 28 days (0.96+/-0.01 versus 0.45+/-0.08, P<0.001). The mural thrombus area was smaller in Ad.CNP-infected grafts than in Ad.LacZ-infected grafts. Neointimal thickening was significantly suppressed in the Ad.CNP group. The in vitro wound assay with human coronary artery endothelial cells revealed significant potentiation of the wound repair process by CNP and atrial natriuretic peptide administration. CONCLUSIONS: Infected Ad.CNP accelerated reendothelialization and suppressed thrombosis and neointimal hyperplasia. The method may potentially prevent vein graft disease in patients undergoing coronary artery revascularization.
BACKGROUND:Vein graft disease limits the late results of coronary revascularization. C-type natriuretic peptide (CNP) inhibits the growth of vascular smooth muscle cells. Given the effects of CNP on cGMP cascade, we hypothesized that transfected CNP genes modulate endothelial repair and thrombogenicity in the vein graft. METHODS AND RESULTS: Autologous rabbit jugular vein grafts were incubated ex vivo in a solution of adenovirus vectors containing CNP gene (Ad.CNP) or Escherichia coli lac Z gene (Ad.LacZ) and then interposed in the carotid artery. Reendothelialization, mural thrombi formation, and intima/media ratio were evaluated on the 14th and 28th postoperative days. More reendothelialization was seen in Ad.CNP-infected grafts than in Ad.LacZ-infected grafts both at 14 days (0.81+/-0.05 versus 0.30+/-0.14, P<0.01) and at 28 days (0.96+/-0.01 versus 0.45+/-0.08, P<0.001). The mural thrombus area was smaller in Ad.CNP-infected grafts than in Ad.LacZ-infected grafts. Neointimal thickening was significantly suppressed in the Ad.CNP group. The in vitro wound assay with human coronary artery endothelial cells revealed significant potentiation of the wound repair process by CNP and atrial natriuretic peptide administration. CONCLUSIONS: Infected Ad.CNP accelerated reendothelialization and suppressed thrombosis and neointimal hyperplasia. The method may potentially prevent vein graft disease in patients undergoing coronary artery revascularization.
Authors: Ehsan Jabbarzadeh; Trevor Starnes; Yusuf M Khan; Tao Jiang; Anthony J Wirtel; Meng Deng; Qing Lv; Lakshmi S Nair; Steven B Doty; Cato T Laurencin Journal: Proc Natl Acad Sci U S A Date: 2008-08-04 Impact factor: 11.205
Authors: Kush M Parmar; H Benjamin Larman; Guohao Dai; Yuzhi Zhang; Eric T Wang; Sripriya N Moorthy; Johannes R Kratz; Zhiyong Lin; Mukesh K Jain; Michael A Gimbrone; Guillermo García-Cardeña Journal: J Clin Invest Date: 2005-12-08 Impact factor: 14.808
Authors: Kristen J Bubb; Aisah A Aubdool; Amie J Moyes; Sarah Lewis; Jonathan P Drayton; Owen Tang; Vedanta Mehta; Ian C Zachary; David J Abraham; Janice Tsui; Adrian J Hobbs Journal: Circulation Date: 2019-03-26 Impact factor: 29.690
Authors: Ramona S Scotland; Marc Cohen; Paul Foster; Matthew Lovell; Anthony Mathur; Amrita Ahluwalia; Adrian J Hobbs Journal: Proc Natl Acad Sci U S A Date: 2005-09-22 Impact factor: 11.205
Authors: Brian Casserly; Jeffrey M Mazer; Alexander Vang; Elizabeth O Harrington; James R Klinger; Sharon Rounds; Gaurav Choudhary Journal: Life Sci Date: 2011-07-27 Impact factor: 5.037