title: Chronic hyperhomocysteinemia causes vascular remodelling by instigating vein phenotype in artery.
abstract: In the present study we tested the hypothesis whether hyperhomocysteinemia, an elevated homocysteine level, induces venous phenotype in artery. To test our hypothesis, we employed wild type (WT) and cystathionine β-synthase heterozygous (+/-) (CBS+/-) mice treatment with or without folic acid (FA). Aortic blood flow and velocity were significantly lower in CBS+/-mice compared to WT. Aortic lumen diameter was significantly decreased in CBS+/-mice, whereas FA treatment normalized it. Medial thickness and collagen were significantly increased in CBS+/-aorta, whereas elastin/collagen ratio was significantly decreased. Superoxide and gelatinase activity was significantly high in CBS+/-aorta vs WT. Western blot showed significant increase in MMP-2, -9,-12, TIMP-2 and decrease in TIMP-4 in aorta. RT-PCR revealed significant increase of vena cava marker EphB4, MMP-13 and TIMP-3 in aorta. We summarize that chronic HHcy causes vascular remodelling that transduces changes in vascular wall in a way that artery expresses vein phenotype.
authors.affiliation: Department of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, Kentucky 40202, USA.
authors.forename: Poulami
authors.initials: P
authors.lastname: Basu
authors.forename: Natia
authors.initials: N
authors.lastname: Qipshidze
authors.forename: Utpal
authors.initials: U
authors.lastname: Sen
authors.forename: Srikanth
authors.initials: S
authors.lastname: Givvimani
authors.forename: Charu
authors.initials: C
authors.lastname: Munjal
authors.forename: Paras K
authors.initials: PK
authors.lastname: Mishra
authors.forename: Suresh C
authors.initials: SC
authors.lastname: Tyagi
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D002908:Chronic Disease; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D003541:Cystathionine beta-Synthase / Q000172:deficiency* / Q000235:genetics; D004549:Elastin / Q000235:genetics / Q000378:metabolism; D036388:Ephrin-B2 / Q000235:genetics / Q000378:metabolism; D005492:Folic Acid / Q000008:administration & dosage* / Q000627:therapeutic use; D015870:Gene Expression / Q000187:drug effects*; D005838:Genotype; D018056:Hemorheology / Q000187:drug effects; D020138:Hyperhomocysteinemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D036224:Receptor, EphB4 / Q000235:genetics / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism; D017539:Tunica Intima / Q000033:anatomy & histology; D014680:Veins / Q000378:metabolism* / Q000473:pathology; D000097792:Tissue Inhibitor of Metalloproteinase-4
chemical_list: D003094:Collagen; D003541:Cystathionine beta-Synthase; D004549:Elastin; D036388:Ephrin-B2; D005492:Folic Acid; D020782:Matrix Metalloproteinases; D036224:Receptor, EphB4; D019716:Tissue Inhibitor of Metalloproteinase-2; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4; C086681:Ephb4 protein, mouse