RATIONALE: Interferon-gamma-inducible protein (IP)-10/CXCL10, an angiostatic and antifibrotic chemokine with an important role in T-cell trafficking, is markedly induced in myocardial infarcts, and may regulate the reparative response. OBJECTIVE: To study the role of IP-10 in cardiac repair and remodeling. METHODS AND RESULTS: We studied cardiac repair in IP-10-null and wild-type (WT) mice undergoing reperfused infarction protocols and examined the effects of IP-10 on cardiac fibroblast function. IP-10-deficient and WT animals had comparable acute infarct size. However, the absence of IP-10 resulted in a hypercellular early reparative response and delayed contraction of the scar. Infarcted IP-10(-/-) hearts exhibited accentuated early dilation, followed by rapid wall thinning during infarct maturation associated with systolic dysfunction. Although IP-10-null and WT mice had comparable cytokine expression, the absence of IP-10 was associated with marked alterations in the cellular content of the infarct. IP-10(-/-) infarcts had more intense infiltration with CD45(+) leukocytes, Mac-2(+) macrophages, and alpha-smooth muscle actin (alpha-SMA)(+) myofibroblasts than WT infarcts but exhibited reduced recruitment of the subpopulations of leukocytes, T lymphocytes and alpha-SMA(+) cells that expressed CXCR3, the IP-10 receptor. IP-10 did not modulate cardiac fibroblast proliferation and apoptosis but significantly inhibited basic fibroblast growth factor-induced fibroblast migration. In addition, IP-10 enhanced growth factor-mediated wound contraction in fibroblast-populated collagen lattices. CONCLUSIONS: Endogenous IP-10 is an essential inhibitory signal that regulates the cellular composition of the healing infarct and promotes wound contraction, attenuating adverse remodeling. IP-10-mediated actions may be due, at least in part, to direct effects on fibroblast migration and function.
RATIONALE: Interferon-gamma-inducible protein (IP)-10/CXCL10, an angiostatic and antifibrotic chemokine with an important role in T-cell trafficking, is markedly induced in myocardial infarcts, and may regulate the reparative response. OBJECTIVE: To study the role of IP-10 in cardiac repair and remodeling. METHODS AND RESULTS: We studied cardiac repair in IP-10-null and wild-type (WT) mice undergoing reperfused infarction protocols and examined the effects of IP-10 on cardiac fibroblast function. IP-10-deficient and WT animals had comparable acute infarct size. However, the absence of IP-10 resulted in a hypercellular early reparative response and delayed contraction of the scar. InfarctedIP-10(-/-) hearts exhibited accentuated early dilation, followed by rapid wall thinning during infarct maturation associated with systolic dysfunction. Although IP-10-null and WT mice had comparable cytokine expression, the absence of IP-10 was associated with marked alterations in the cellular content of the infarct. IP-10(-/-) infarcts had more intense infiltration with CD45(+) leukocytes, Mac-2(+) macrophages, and alpha-smooth muscle actin (alpha-SMA)(+) myofibroblasts than WT infarcts but exhibited reduced recruitment of the subpopulations of leukocytes, T lymphocytes and alpha-SMA(+) cells that expressed CXCR3, the IP-10 receptor. IP-10 did not modulate cardiac fibroblast proliferation and apoptosis but significantly inhibited basic fibroblast growth factor-induced fibroblast migration. In addition, IP-10 enhanced growth factor-mediated wound contraction in fibroblast-populated collagen lattices. CONCLUSIONS: Endogenous IP-10 is an essential inhibitory signal that regulates the cellular composition of the healing infarct and promotes wound contraction, attenuating adverse remodeling. IP-10-mediated actions may be due, at least in part, to direct effects on fibroblast migration and function.
Authors: Jennifer H Dufour; Michelle Dziejman; Michael T Liu; Josephine H Leung; Thomas E Lane; Andrew D Luster Journal: J Immunol Date: 2002-04-01 Impact factor: 5.422
Authors: Sima T Tarzami; Wenfeng Miao; Kartik Mani; Lillie Lopez; Stephen M Factor; Joan W Berman; Richard N Kitsis Journal: Circulation Date: 2003-10-20 Impact factor: 29.690
Authors: Andrew M Tager; Richard L Kradin; Peter LaCamera; Scott D Bercury; Gabriele S V Campanella; Carol P Leary; Vasiliy Polosukhin; Long-Hai Zhao; Hideo Sakamoto; Timothy S Blackwell; Andrew D Luster Journal: Am J Respir Cell Mol Biol Date: 2004-06-17 Impact factor: 6.914
Authors: Oliver Dewald; Guofeng Ren; Georg D Duerr; Martin Zoerlein; Christina Klemm; Christine Gersch; Sophia Tincey; Lloyd H Michael; Mark L Entman; Nikolaos G Frangogiannis Journal: Am J Pathol Date: 2004-02 Impact factor: 4.307
Authors: A L Angiolillo; C Sgadari; D D Taub; F Liao; J M Farber; S Maheshwari; H K Kleinman; G H Reaman; G Tosato Journal: J Exp Med Date: 1995-07-01 Impact factor: 14.307
Authors: Edward J Goetzl; Mei-Chuan Huang; Junko Kon; Kalpesh Patel; Janice B Schwartz; Katharine Fast; Luigi Ferrucci; Karen Madara; Dennis D Taub; Dan L Longo Journal: FASEB J Date: 2010-05-07 Impact factor: 5.191
Authors: C A Danilo; E Constantopoulos; L A McKee; H Chen; J A Regan; Y Lipovka; S Lahtinen; L K Stenman; T-V V Nguyen; K P Doyle; M J Slepian; Z I Khalpey; J P Konhilas Journal: Benef Microbes Date: 2017-04-14 Impact factor: 4.205
Authors: Joshua Mayourian; Delaine K Ceholski; David M Gonzalez; Timothy J Cashman; Susmita Sahoo; Roger J Hajjar; Kevin D Costa Journal: Circ Res Date: 2018-01-05 Impact factor: 17.367