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Mechanisms underlying the impairment of ischemia-induced neovascularization in matrix metalloproteinase 2-deficient mice.
Circ Res. 2007 Mar 30; 100(6):904-13.CircR

Abstract

Matrix metalloproteinases (MMPs) have been implicated in the process of neovascularization. However, the exact roles of individual MMPs in vessel formation are poorly understood. To study the putative role of MMP-2 in ischemia-induced neovascularization, a hindlimb ischemia model was applied to MMP-2(+/+) and MMP-2(-/-) mice. Serial laser Doppler blood-flow analysis revealed that the recovery of the ischemic/normal blood-flow ratio in MMP-2(-/-) young and old mice remained impaired throughout the follow-up period. At day 35, microangiography and anti-l-lectin immunohistochemical staining revealed lesser developed collateral vessels and capillary formation in both old and young MMP-2(-/-) mice compared with the age-matched MMP-2(+/+) mice. An aortic-ring culture assay showed a markedly impaired angiogenic response in MMP-2(-/-) mice, which was partially recovered by supplementation of the culture medium with recombinant MMP-2. Aorta-derived endothelial cells or bone marrow-derived endothelial progenitor cell (EPC)-like c-Kit(+) cells from MMP-2(-/-) showed marked impairment of invasive or/and proliferative abilities. At day 7, plasma and ischemic tissues of vascular endothelial growth factor protein were reduced in MMP-2(-/-). Flow cytometry showed that the numbers of EPC-like CD31(+)c-Kit(+) cells in peripheral blood markedly decreased in MMP-2-deficient mice. Transplantation of bone marrow-derived mononuclear cells from MMP-2(+/+) mice restored neovascularization in MMP-2(-/-) young mice. These data suggest that MMP-2 deficiency impairs ischemia-induced neovascularization through a reduction of endothelial cell and EPC invasive and/or proliferative activities and EPC mobilization.

Authors+Show Affiliations

Department of Geriatrics, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan. xianwu@med.nagoya-u.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17322177

Citation

Cheng, Xian Wu, et al. "Mechanisms Underlying the Impairment of Ischemia-induced Neovascularization in Matrix Metalloproteinase 2-deficient Mice." Circulation Research, vol. 100, no. 6, 2007, pp. 904-13.
Cheng XW, Kuzuya M, Nakamura K, et al. Mechanisms underlying the impairment of ischemia-induced neovascularization in matrix metalloproteinase 2-deficient mice. Circ Res. 2007;100(6):904-13.
Cheng, X. W., Kuzuya, M., Nakamura, K., Maeda, K., Tsuzuki, M., Kim, W., Sasaki, T., Liu, Z., Inoue, N., Kondo, T., Jin, H., Numaguchi, Y., Okumura, K., Yokota, M., Iguchi, A., & Murohara, T. (2007). Mechanisms underlying the impairment of ischemia-induced neovascularization in matrix metalloproteinase 2-deficient mice. Circulation Research, 100(6), 904-13.
Cheng XW, et al. Mechanisms Underlying the Impairment of Ischemia-induced Neovascularization in Matrix Metalloproteinase 2-deficient Mice. Circ Res. 2007 Mar 30;100(6):904-13. PubMed PMID: 17322177.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanisms underlying the impairment of ischemia-induced neovascularization in matrix metalloproteinase 2-deficient mice. AU - Cheng,Xian Wu, AU - Kuzuya,Masafumi, AU - Nakamura,Kae, AU - Maeda,Keiko, AU - Tsuzuki,Michitaka, AU - Kim,Weon, AU - Sasaki,Takeshi, AU - Liu,Zexuan, AU - Inoue,Natsuo, AU - Kondo,Takahisa, AU - Jin,Hai, AU - Numaguchi,Yasushi, AU - Okumura,Kenji, AU - Yokota,Mitsuhiro, AU - Iguchi,Akihisa, AU - Murohara,Toyoaki, Y1 - 2007/02/22/ PY - 2007/2/27/pubmed PY - 2007/4/14/medline PY - 2007/2/27/entrez SP - 904 EP - 13 JF - Circulation research JO - Circ Res VL - 100 IS - 6 N2 - Matrix metalloproteinases (MMPs) have been implicated in the process of neovascularization. However, the exact roles of individual MMPs in vessel formation are poorly understood. To study the putative role of MMP-2 in ischemia-induced neovascularization, a hindlimb ischemia model was applied to MMP-2(+/+) and MMP-2(-/-) mice. Serial laser Doppler blood-flow analysis revealed that the recovery of the ischemic/normal blood-flow ratio in MMP-2(-/-) young and old mice remained impaired throughout the follow-up period. At day 35, microangiography and anti-l-lectin immunohistochemical staining revealed lesser developed collateral vessels and capillary formation in both old and young MMP-2(-/-) mice compared with the age-matched MMP-2(+/+) mice. An aortic-ring culture assay showed a markedly impaired angiogenic response in MMP-2(-/-) mice, which was partially recovered by supplementation of the culture medium with recombinant MMP-2. Aorta-derived endothelial cells or bone marrow-derived endothelial progenitor cell (EPC)-like c-Kit(+) cells from MMP-2(-/-) showed marked impairment of invasive or/and proliferative abilities. At day 7, plasma and ischemic tissues of vascular endothelial growth factor protein were reduced in MMP-2(-/-). Flow cytometry showed that the numbers of EPC-like CD31(+)c-Kit(+) cells in peripheral blood markedly decreased in MMP-2-deficient mice. Transplantation of bone marrow-derived mononuclear cells from MMP-2(+/+) mice restored neovascularization in MMP-2(-/-) young mice. These data suggest that MMP-2 deficiency impairs ischemia-induced neovascularization through a reduction of endothelial cell and EPC invasive and/or proliferative activities and EPC mobilization. SN - 1524-4571 UR - https://www.unboundmedicine.com/medline/citation/17322177/Mechanisms_underlying_the_impairment_of_ischemia_induced_neovascularization_in_matrix_metalloproteinase_2_deficient_mice_ L2 - https://www.ahajournals.org/doi/10.1161/01.RES.0000260801.12916.b5?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -