Inhibited angiogenesis in aging: a role for TIMP-2.
Inhibited angiogenesis in aging: a role for TIMP-2.
复制标题
抑制衰老过程中的血管生成：TIMP-2 的作用。
DOI：
10.1093/gerona/58.9.b798
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Reed,MayJ
中科院分区：
文献类型：
--
作者：
Koike,Teruhiko;Vernon,RobertB;Gooden,MichelD;Sadoun,Eman;Reed,MayJ
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.
