Table 1. Signaling molecules modulating extracellular matrix dynamic changes in myocardial infarction.

Molecule	Localization	Expression Time	Effect	Refs.
Matricellular Proteins
Tenascin-C	Infarcted myocardium, border zone, remodeling myocardium	Early post-infarct period (proliferative phase of myocardial healing)	Stimulates collagen synthesis; Induces fibroblast migration and differentiation; Promotes inflammation and angiogenesis	[102-105]
Tenascin-X	Not known	Not known	Promotes collagen deposition; Maintains ECM preservation; Contributes to inhibition of MMP-2 and MMP-9 activity	[106, 107]
Trombospondin-1	Infarct border zone	Early post-infarct period (inflammatory phase of myocardial healing)	Activates TGF-β1; Modulates fibroblast migration and differentiation; Promotes fibrogenesis; Suppresses inflammatory response; Inhibits angiogenesis; Inhibits MMPs	[56, 121, 122]
Trombospondin-2	Not known	Late post-infarct period after trombospondin-1 level decreases	Exerts anti-inflammatory effects; Reduces angiogenesis; Inhibits MMPs; Modulates fibroblast interactions with fibronectin	[121, 123, 124]
Osteonectin	Infarcted myocardium, non-infarcted myocardium	Early and late post-infarct period (3rd - 14th day)	Modulates activity of TGF-β, fibroblasts growth factor, platelets growth factor, vascular endothelial growth factor; Induces myocardial cells de-adhesion; Promotes angiogenesis; Regulates assembly of newly-formed collagen	[108-111]
Osteopontin	Infarcted myocardium, non-infarcted myocardium	Early and late post-infarct period (1st - 28th day)	Induces collagen synthesis and organization; Inhibits cell apoptosis; Modulates growth factor signaling; Activates angiogenesis	[114-119]
Periostin	Infarcted myocardium, border zone, remodeling myocardium	Early and late post-infarct period (3rd - 28th day)	Promotes fibroblasts migration and differentiation; Stimulates fibrillogenesis	[125-128]
CCN-2	Infarcted myocardium	Early and late post-infarct period (7th-28th day)	Activates TGF-β1 signaling pathways; Stimulates angiogenesis; Promotes fibroblast migration and differentiation; Exerts cardioprotective effect	[130-133]
Proteins with matricellular function
Biglycan	Infarcted myocardium, border zone	Early and late post-infarct period (2nd – 28th day) with peaking at 14th day	Stimulates collagen deposition and appropriate cross-linking; Regulates fibroblast phenotype and function; Decreases ventricular dilation; Attenuates ventricular rupture; Modulates scar organization	[100, 135]
Decorin	Infarcted myocardium, border zone	Early and late post-infarct period (7th-28thday) with peaking at 14th day	Regulates collagen fibrillogenesis and proper matrix assembly; Decreases infarct size and ventricular hypertrophy; Diminishes left ventricular dilation; Promotes scar organization	[100, 134]
Molecule	Localization	Expression Time	Effect	Refs.
Syndecans	Infarcted myocardium	Early post-infarct period (24h – 7th day peak)	Prevent excessive matrix degradation; Enhance myofibroblast transdifferentiation; Stimulate growth factor-dependent endothelial cell proliferation; Promote angiogenesis; Reduce myocardial inflammation and fibrosis; Inhibit cardiomyocyte apoptosis	[138, 139]
Galectins	Infarcted myocardium	Early post-infarct period (2nd -14th day)	Induce fibroblast proliferation; Promote matrix deposition; Stimulate macrophage migration	[136, 137]
Growth factors
Transforming growth factor beta	Predominantly infarct border zone	Early and late post-infarct period (3rd - 28th day)	Promotes myofibroblast differentiation; Increases collagen and fibronectin synthesis; Activates TIMP; Stimulates cardiomyocyte hypertrophy; Induces mononuclear cells chemotaxis; Promotes angiogenesis; Reduces oxidative stress; Protects cardiomyocytes from apoptosis	[54, 56, 120]
Fibroblast growth factor	Infarcted myocardium, border zone	Early and late post-infarct period (7th-28th day)	Promotes proliferation of fibroblasts, endothelial cells, smooth muscle cells; Regulatesprocesses of cell survival, migration, differentiation and apoptosis; Stimulates angiogenesis; Attenuates fibroblast proliferation and collagen deposition	[59, 60]
Platelet derived growth factor	Infarcted myocardium	Early and late post-infarct period (7th-28th day)	Regulates fibroblast migration, proliferation and transformation; Promotes fibrogenesis; Induces TGF-β synthesis; Facilitates stabilization and maturation of neovessels; Promotes resolution of inflammation	[53, 62]
Vascular endothelial growth factor	Infarcted myocardium, border zone	Early and late post-infarct period (24 hours – 6 weeks)	Promotes angiogenesis and proliferation of endothelial cells; Inhibits cardiomyocyte apoptosis; Enhances myocardial contractility	[63, 64]
Cardiotrophin-1	Predominantly infarcted myocardium	Early and late pot-infarct period (24 hours – 8 weeks)	Induces cardiomyocyte survival; Inhibits cardiomyocyte apoptosis; Attenuates ischemia/reperfusion myocardium injury; Maintains myocardial contractility by stimulation of cardiomyocyte hypertrophy; Stimulates fibroblast migration and proliferation; Induces bone marrow stem cells migration; Stimulates synthesis of multiple extracellular matrix proteins	[65, 80, 81]