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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:2443.)
© 2007 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Genomic Changes in Regenerated Porcine Coronary Arterial Endothelial Cells

Mary Y.K. Lee; Hung-Fat Tse; Chung-Wah Siu; Shu-Guang Zhu; Ricky Y.K. Man; Paul M. Vanhoutte

From the Department of Pharmacology (M.Y.K.L., R.Y.K.M., P.M.V.) and the Cardiology Division, Department of Medicine (H.F.T., C.W.S., S.G.Z.), Li Ka Shing Faculty of Medicine, The University of Hong Kong.

Correspondence to Paul M. Vanhoutte, L2-48, Department of Pharmacology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 2/F Laboratory Block, 21 Sassoon Road, Pokfulam, Hong Kong. E-mail vanhoutt{at}hkucc.hku.hk

Objective— Genomic changes were defined in cultures of regenerated porcine coronary endothelial cells to explain the alterations that underlie their dysfunction.

Methods and Results— Regeneration of the endothelium was triggered in vivo by endothelial balloon denudation. After 28 days, both left circumflex (native cells) and left anterior descending (regenerated cells) coronary arteries were dissected, their endothelial cells harvested, and primary cultures established. The basal cyclic GMP production was reduced in regenerated cells without significant reduction in the response to bradykinin and A23187. The mRNA expression levels in both native and regenerated cells were measured by microarray and RT-PCR. The comparison revealed genomic changes related to vasomotor control (cyclooxygenase-1, angiotensin II receptor), coagulation (F2 and TFPI), oxidative stress (Mn SOD, GPX3, and GSR), lipid metabolism (PLA2 and HPGD), and extracellular matrix (MMPs). A-FABP and MMP7 were induced by regeneration. RT-PCR revealed upregulation of A-FABP and downregulation of eNOS and TR. The differential gene expression profiles were confirmed at the protein level by Western blotting for eNOS, F2, Mn SOD, MMP7, and TR.

Conclusions— Cultures from regenerated coronary endothelial cells exhibit genomic changes explaining endothelial dysfunction and suggesting facilitation of coagulation, lipid peroxidation, and extracellular matrix remodeling.

Genomic changes were determined in cultured regenerated endothelial cells. cGMP production was reduced. Changes in mRNA expression related to vasomotor control, coagulation, oxidative stress, extracellular matrix, and lipid were confirmed by Western blotting for eNOS, F2, Mn SOD, matrix metalloproteinase 7, and TR. These findings reveal linkages between regeneration and endothelial dysfunction.

Key Words: endothelial regeneration • genomics • nitric oxide • ROS • coagulation • extracellular matrix • lipids

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