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DDAH‐2 & eNOS in Mesenteric Vascular Remodeling : Role of Fenugreek
Author(s) -
Munjal Charu,
Falcone Jeff c,
Qipshidze Natia,
Mishra Paras,
Tyagi Suresh C
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.774.7
Subject(s) - enos , endocrinology , medicine , matrix metalloproteinase , vasodilation , nitric oxide , elastin , endothelial dysfunction , chemistry , blood flow , tissue inhibitor of metalloproteinase , nitric oxide synthase , pathology
Although mesenteric vessels played a crucial role in vascular remodeling, the mechanism was unclear. A critical factor, for the development of hypertension was increase in resistance in splanchnic blood flow by endothelial dysfunction. Increased homocysteine (Hcy) levels known as hyperhomocysteinimia(HHcy), causing vascular dysfunction. DDAH degrades ADMA, an endogenous inhibitor of nitric oxide synthetas (eNOS). Matrix metalloprotease (MMP) caused an increase in collagen/elastin ratio. Fenugreek (FG) primarily used as antidiabetic, also reported to have restoration of endothelial function. We hypothesized Hcy decreased mesentery blood flow in part by imbalancing the MMP/TIMP axis and decreasing the eNOS/DDAH activity. The treatment with FG mitigated blood flow and hypertension. To test this hypothesis we used WT(b) WT+ FG (c) WT+High Meth diet (d)WT+ High Meth diet+ FG, i.p. injection. The protein expression of MMPs, TIMPs and redox proteins were measured by Western blot. MMP‐2, 9 activities was measured by zymography. Tissue sections were used for to study elastin/collagen ratio. The data suggested Hcy decreased blood flow and matrix disruption by decreasing DDAH‐2, eNOS expression, FG ameliorated it. Therefore we concluded that FG migrate, decreased mesentery blood flow, MMP/TIMP axis distruption, decreasing the eNOS/DDAH activity by Hcy.