title: X-ray imaging of differential vascular density in MMP-9-/-, PAR-1-/+, hyperhomocysteinemic (CBS-/+) and diabetic (Ins2-/+) mice.
abstract: Although protease activated receptor-1 (PAR-1) and matrix metalloproteinase-9 (MMP-9) play significant role in vascular remodelling in hyperhomocysteinemia (HHcy due to cystathionine beta synthase deficiency, CBS-/+) and diabetes, mechanism remains nebulous. We hypothesized that differential vascular density and remodelling in different vascular beds in HHcy and diabetes were responsible for an adaptive metabolic homeostasis during the pathogenesis. To test this hypothesis, vascular density in mice lacking PAR-1, MMP-9, CBS and Insulin-2 gene mutant (Ins2-/+, Akita) was measured and compared with wild type (WT, C57BL/6J) mice. The vascular density was detected by x-ray angiography using KODAK 4000 MM image station, using barium sulphate as contrasting agent. The % vascular density in the hearts of WT, CBS-/+ (HHcy), MMP-9-/-, PAR-1-/+ and Ins2-/+ (type-1 diabetes) was 100 ± 2.8, 85 ± 3.3, 90 ± 3.3, 95 ± 3.8 and 73 ± 1.7, respectively. The vascular density in CBS-/+ and Akita hearts decreased while it was increased in lungs of CBS-/+ and MMP-9-/-.There was decreased vascular density in liver and kidney of Akita mice. Vascular density in brain, kidney and mesentery was decreased in CBS-/+ mice. These findings support the notation that metabolic derangement in diabetes and HHcy causes the chronic decline and/or rarefaction in vascular density.
authors.affiliation: Department of Physiology and Biophysics, University of Louisville School of Medicine, KY 40202, USA.
authors.forename: S
authors.initials: S
authors.lastname: Givvimani
authors.forename: U
authors.initials: U
authors.lastname: Sen
authors.forename: N
authors.initials: N
authors.lastname: Tyagi
authors.forename: C
authors.initials: C
authors.lastname: Munjal
authors.forename: S C
authors.initials: SC
authors.lastname: Tyagi
mesh_terms: D000792:Angiography; D000818:Animals; D001466:Barium Sulfate / Q000032:analysis; D001808:Blood Vessels / Q000473:pathology; D001921:Brain / Q000098:blood supply; D003541:Cystathionine beta-Synthase / Q000172:deficiency / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D020138:Hyperhomocysteinemia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D020780:Matrix Metalloproteinase 9 / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009929:Organ Size / Q000235:genetics; D044463:Receptor, PAR-1 / Q000172:deficiency / Q000235:genetics; D012079:Renal Circulation; D013152:Splanchnic Circulation; D014965:X-Rays
chemical_list: D044463:Receptor, PAR-1; D001466:Barium Sulfate; D020780:Matrix Metalloproteinase 9; D003541:Cystathionine beta-Synthase