Rationale: Interferon-–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 -smooth muscle actin (-SMA)⁺ myofibroblasts than WT infarcts but exhibited reduced recruitment of the subpopulations of leukocytes, T lymphocytes and -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.