TY - JOUR
T1 - Vein graft arterialization causes differential activation of mitogen-activated protein kinases
AU - Saunders, Paul C.
AU - Pintucci, Giuseppe
AU - Bizekis, Costas S.
AU - Sharony, Ram
AU - Hyman, Kevin M.
AU - Saponara, Fiorella
AU - Baumann, F. Gregory
AU - Grossi, Eugene A.
AU - Colvin, Stephen B.
AU - Mignatti, Paolo
AU - Galloway, Aubrey C.
N1 - Funding Information:
This work was supported by funds from the Seymour Cohn Foundation for Cardiovascular Surgery Research.
PY - 2004/5
Y1 - 2004/5
N2 - Objective: Vascular injury results in activation of the mitogen-activated protein kinases-extracellular-signal regulated kinases, c-jun N-terminal kinase, and p38MAPK-which have been implicated in cell proliferation, migration, and apoptosis. The goal of this study was to characterize mitogen-activated protein kinase activation in arterialized vein grafts. Methods: Carotid artery bypass using reversed external jugular vein was performed in 29 dogs. Vein grafts were harvested after 30 minutes and 3, 8, and 24 hours, and 4, 7, 14, and 28 days. Contralateral external jugular vein and external jugular vein interposition vein-to-vein grafts were used as controls. Vein graft extracts were analyzed for extracellular-signal regulated kinases, c-jun N-terminal kinase, and p38MAPK activation. Proliferating cell nuclear antigen expression was investigated as a parameter of cell proliferation. Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate nick end labeling staining and intimal hyperplasia by morphometric examination of tissue sections. Results: Significant intimal hyperplasia was observed at 28 days. Over the time points studied, vein graft arterialization resulted in bimodal activation of both extracellular-signal regulated kinase and p38MAPK (30 minutes through 3 hours; 4 days) but did not induce activation of c-jun N-terminal kinase. Proliferating cell nuclear antigen expression increased from days 1 through 28, and apoptosis increased between 8 and 24 hours. Conclusion: Vein graft arterialization induces bimodal activation of extracellular-signal regulated kinase and p38MAPK; however, in contrast with what is described in arterial injury, it does not induce c-jun N-terminal kinase activation. These results provide the first comprehensive characterization of the mitogen-activated protein kinase signaling pathways activated in vein graft arterialization and identify mitogen-activated protein kinases as potential mediators of vein graft remodeling and subsequent intimal hyperplasia.
AB - Objective: Vascular injury results in activation of the mitogen-activated protein kinases-extracellular-signal regulated kinases, c-jun N-terminal kinase, and p38MAPK-which have been implicated in cell proliferation, migration, and apoptosis. The goal of this study was to characterize mitogen-activated protein kinase activation in arterialized vein grafts. Methods: Carotid artery bypass using reversed external jugular vein was performed in 29 dogs. Vein grafts were harvested after 30 minutes and 3, 8, and 24 hours, and 4, 7, 14, and 28 days. Contralateral external jugular vein and external jugular vein interposition vein-to-vein grafts were used as controls. Vein graft extracts were analyzed for extracellular-signal regulated kinases, c-jun N-terminal kinase, and p38MAPK activation. Proliferating cell nuclear antigen expression was investigated as a parameter of cell proliferation. Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate nick end labeling staining and intimal hyperplasia by morphometric examination of tissue sections. Results: Significant intimal hyperplasia was observed at 28 days. Over the time points studied, vein graft arterialization resulted in bimodal activation of both extracellular-signal regulated kinase and p38MAPK (30 minutes through 3 hours; 4 days) but did not induce activation of c-jun N-terminal kinase. Proliferating cell nuclear antigen expression increased from days 1 through 28, and apoptosis increased between 8 and 24 hours. Conclusion: Vein graft arterialization induces bimodal activation of extracellular-signal regulated kinase and p38MAPK; however, in contrast with what is described in arterial injury, it does not induce c-jun N-terminal kinase activation. These results provide the first comprehensive characterization of the mitogen-activated protein kinase signaling pathways activated in vein graft arterialization and identify mitogen-activated protein kinases as potential mediators of vein graft remodeling and subsequent intimal hyperplasia.
UR - http://www.scopus.com/inward/record.url?scp=2342435175&partnerID=8YFLogxK
U2 - 10.1016/j.jtcvs.2003.07.017
DO - 10.1016/j.jtcvs.2003.07.017
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C2 - 15115983
AN - SCOPUS:2342435175
SN - 0022-5223
VL - 127
SP - 1276
EP - 1284
JO - Journal of Thoracic and Cardiovascular Surgery
JF - Journal of Thoracic and Cardiovascular Surgery
IS - 5
ER -
