Table 5.
Inflammatory signals involved in the pathogenesis of cardiac rupture
| Gene/Protein | Mechanism | Ref. |
|---|---|---|
| Cyclic GMP-AMP synthase (cGAS) | cGAS was suggested to cause rupture following MI by acting as a pattern recognition receptor that stimulates proinflammatory programs and by inhibiting activation of reparative macrophages. | (8) |
| CD8 | Mice deficient in functional CD8+ T cells had improved survival but increased incidence of cardiac rupture, suggesting that CD8+ T cells may be involved in effective scar formation. | (43) |
| IL-35 | IL-35 protected from post-MI cardiac rupture, promoting reparative macrophage responses and improving repair. | (46) |
| Toll-like receptor 7 (TLR7) | TLR7 was implicated in cardiac rupture through effects on leukocyte cytokine expression. | (14) |
| Muscle atrophy F-box (MAFbx) | The E3 ubiquitin ligase MAFbx was implicated in cardiac rupture post-MI, presumably by inducing inflammatory cell infiltration. | (87) |
| Heat shock protein-B1 (HSPB1) | Cardiomyocyte-specific HSPB1 signaling was found to protect from post-MI cardiac rupture by inhibiting inflammatory activation. | (93) |
| 12/15-Lipoxygenase (LOX) | 12/15 LOX was implicated in the pathogenesis of cardiac rupture, presumably by enhancing synthesis of proinflammatory lipid mediators. | (48) |
| Apoptosis inhibitor of macrophage (AIM) | AIM was implicated in the pathogenesis of post-MI cardiac rupture, presumably through recruitment of proinflammatory macrophages. | (45) |
| CD36 | Activation of a CD36-Mertk axis protects from cardiac rupture by promoting phagocytosis of dead cells by activated macrophages. | (15) |
| Granulocyte/macrophage colony-stimulating factor (GM-CSF) | Fibroblast-derived GM-CSF was implicated in post-MI cardiac rupture, presumably through recruitment of proteolytic/inflammatory neutrophils and monocytes. | (2) |
| Glucocorticoid receptor (GR) | Inactivation of GR altered the functional differentiation of monocyte-derived macrophages in the infarcted myocardium and was suggested to cause higher rupture-related mortality. | (26) |
| β-Adrenergic receptor (β2AR) | Myeloid β2ARKO (through bone marrow transplantation) mice displayed 100% mortality resulting from post-MI cardiac rupture. β2ARKO mice had reduced leukocyte infiltration in infarcted hearts. | (30) |
| Calpastatin | Male mice overexpressing calpastatin had increased rates of post-MI cardiac rupture. KO mice exhibited reduced infiltration of M2 macrophages and CD4+ T cells. | (91) |
| TGFβ receptor 1 (TβRI) | Conditional cardiomyocyte specific TGFβ receptor 1 knockout displayed marked decline in neutrophil recruitment and attenuated MMP9 activity with reduced post-MI cardiac rupture rates. | (75) |
| MIF | MIF-deficient mice had lower rates of post-MI cardiac rupture, associated with reduced myocardial leukocyte infiltration, and reduced activity of MMP-2 and -9, p38, and JNK MAPK. | (96) |
| IL-23 | IL-23KO mice exhibited increased post-MI cardiac rupture rates, presumably through higher expression of proinflammatory cytokines and increased infiltration with immune cells. | (77) |
| Haptoglobin | Haptoglobin-deficient mice displayed increased post-MI cardiac rupture rates, presumably through increased leukocyte infiltration in the infarct, reduced PAI-1 activity and enhanced VEGFα expression. | (4) |
| 5-Lipoxygenase | 5-Lipoxygenase-null mice exhibited higher post-MI cardiac rupture rates, with more abundant proinflammatory macrophages and decreased collagen deposition and fibroblast migration. | (7) |
| D6 | D6-null mice exhibited increased post-MI cardiac rupture rates, presumably through enhanced infiltration of neutrophils and Ly6Chi monocytes and increased MMP-9 and -2 activity in the infarct. | (12) |
| Fibulin-2 | Fibulin-2 mice exhibited lower post-MI cardiac rupture rates with attenuated inflammatory cell infiltration and MMP-2 and -9 expression. | (84) |
| GDF-15 | GDF-15 deficient mice had enhanced recruitment of PMN leukocytes associated with increased rates of post-MI cardiac rupture. | (50) |
| Syndecan-4 (Syn4) | Syn4 KO mice exhibited increased rates of post-MI cardiac rupture, associated with suppressed inflammation and impaired granulation tissue formation in the heart after MI. | (64) |
| Gp130 | Cardiomyocyte-specific Gp130 KO was associated with increased post-MI cardiac rupture rates, presumably through enhanced STAT3 activation and increased expression of IL-6. | (38) |
| Timp4 | Timp4−/− mice had increased post-MI cardiac rupture rates, associated with increased neutrophil infiltration. | (53) |
| Class A macrophage scavenger receptor (SR-A) | SR-A−/− mice exhibited higher rates of post-MI cardiac rupture, presumably due to augmented gelatinolytic activity, increased MMP-9 and TNFα and reduced IL-10 mRNA in the infarcted myocardium. | (85) |
| TNFα | TNFα−/− mice exhibited markedly reduced post-MI cardiac rupture rates, presumably due to reduced inflammatory cell infiltration, cytokines, and MMP-9 and -2 expression in the infarct. | (81) |
| FrzA | FrzA overexpression protected from rupture, attenuating leukocyte infiltration and reducing MMP9 and MMP2 expression in the infarct. | (5) |
MI, myocardial infarction; KO, knockout.