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Int J Physiol Pathophysiol Pharmacol 2011;3(4):266-279.
Remodeling in vein expresses arterial phenotype in hyperhomocysteinemia
Poulami Basu, Natia Qipshidze, Suresh C. Tyagi, Utpal Sen
Department of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, Kentucky, USA.
Received October 6, 2011; accepted October 26, 2011; Epub November 15, 2011; Published December 15, 2011
Abstract: Accumulating evidences suggest that homocysteine, a non-protein amino acid, is involved in vessel remodeling and blood
flow at elevated level, although the exact mechanism is unclear. Here we hypothesized that homocysteine affects vein in such a way
that vein develops arterial phenotype. We tested our hypothesis employing wild type (WT, C57BL/6J) and CBS+/- (cystathionine β-
synthase heterozygote, a genetic model of hyperhomocysteinemia) supplemented with or without folic acid (FA, a homocysteine
lowering agent). Vena cava blood flow was measured by ultrasound transonic flow probe. Tissue collagen and elastin were detected by
histochemistry. Super oxide was detected by dihydroethidium (DHE) staining. Expressions of MMP-2, -9, -12, TIMP -2,- 4, were
measured by Western blot. MMP-13, TIMP-1, -3, and vein and aortic markers, EphB4 and EphrinB2, respectively were measured by RT-
PCR. The results indicated relatively low blood flow in CBS+/- mice, although FA treatment did not alter this flow in CBS+/- mice.
Significant increase of collagen/elastin ratio was observed in the CBS+/- group and FA treatment normalized this ratio. A relatively
increased content of super oxide and gelatinase activity was observed in CBS+/- vena cava vs WT and normalized by FA treatment.
Western blot analyses showed significant increase in MMP-9,-12 and decrease in TIMP-2, -4 expressions. Expressions of MMP-13,
TIMP-1 and -3, Ephrin B2 were increased, whereas EphB4 was decreased with reverse change in FA treatment, with no change in MMP-
13 and TIMP-1. We conclude that chronic HHcy causes vascular remodeling that expresses arterial phenotype in vein. (IJPPP1110001).
Keywords: Homocysteine, vascular remodeling, matrix, metalloproteinase, collagen, elastin
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Address all correspondence to:
Utpal Sen, PhD
500 South Preston St, A-1115
University of Louisville
Louisville, KY 40202, USA.