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  • Inhibited angiogenesis in aging: a role for TIMP-2. 14528035

    Factors responsible for age-associated impairment of angiogenesis are poorly understood. We observed that in aged mice, new fibrovascular tissue within subcutaneous polyvinyl alcohol sponges expressed more tissue inhibitor of metalloproteinases (TIMP)-2 than did corresponding tissue from young mice. In complementary studies in vitro, we utilized young and aged human microvascular endothelial cell lines (hmEC36 and hmEC90, respectively) and compared their morphogenetic capacity within three-dimensional collagen. HmEC90 exhibited poor formation of tubular, capillary-like structures in vitro, diminished expression of active matrix metalloproteinase (MMP)-2, and similar or lesser amounts of MT1-MMP relative to hmEC36. Correspondingly, the MMP inhibitor GM6001 decreased tubulogenesis by hmEC36 to levels observed for hmEC90. In vitro, hmEC90 expressed similar quantities of TIMP-1, but more TIMP-2 than did hmEC36. Accordingly, purified TIMP-2 inhibited tubulogenesis by hmEC36. Collectively, our studies indicate that elevated levels of TIMP-2 modulate decreased angiogenesis in aged tissues, most likely via TIMP-2-mediated inhibition of MMP-2 and MT1-MMP.
    Document Type:
    Reference
    Product Catalog Number:
    MAB3310
    Product Catalog Name:
    Anti-TIMP-2 Antibody, clone 67-4H11
  • Macromolecular source as dependent on osmotic pressure and water source: effects on bovine in vitro embryo development and quality 15141434

    This study evaluated the protective effect of protein, as dependent on osmolarity, and the quality of water sources used to prepare embryo culture media. In Experiment 1, two concentrations of NaCl were used to obtain culture media with normal (280 mOSM) and low (245 mOSM) osmolarity, each supplemented with either bovine serum albumin (BSA) or polyvinyl alcohol (PVA). Low osmolarity improved blastocyst rates in the presence of BSA (P < 0.01) and tended to do it in medium containing PVA (P < 0.07). Furthermore, low osmolarity allowed PVA to increase inner cell mass (ICM) numbers and ICM/total cell rate (P < 0.05), while trophectoderm (TE) and total cell counts tended to decrease (P < 0.08). In Experiment 2, culture media were prepared with two water sources (Milli-Q and Sigma-W3500-) in combination with BSA or PVA. Both water sources yielded similar embryo development rates, but in the presence of BSA, Milli-Q water produced embryos with increased ICM/total cells rates (P < 0.05). On the contrary, Sigma water tended to increase trophectoderm cell counts (P < 0.08). In conclusion, the present study showed that low osmolarity is beneficial to embryo development and combinations of macromolecule and osmolarity influence trophectoderm differentiation. Both Milli-Q and Sigma supported embryo development at comparable rates, although in the presence of BSA, blastocysts obtained in the medium prepared with Milli-Q water had superior quality in terms of ICM/total cells rates.
    Document Type:
    Reference
    Product Catalog Number:
    Multiple
    Product Catalog Name:
    Multiple