Table 2.
ACKR3 in cardiovascular diseases.
| Atheroprotective effects | |
| Ubiquitous (CAG-Cre+Cxcr7floxApoe−/−
) and conditional Ackr3-/-
(CAG-CreERTM Cxcr7flox/flox Apoe−/−
) Increased serum cholesterol levels and hyperlipidemia-induced monocytosis |
(64) |
| Hyperlipidemic Apoe-/-
and LdlR-/- mice treated with agonist CCX771 Reduced serum cholesterol, triglyceride levels and inhibited lesion formation after vascular injury |
(65) |
| Hyperlipidemic Apoe-/- Ackr3-/-
mice Increased neointimal formation and lesional macrophage accumulation after vascular injury |
(65) |
| Endothelial Ackr3-/- (Cxcr7flox/flox Cdh5-Cre)
Increased neointimal formation and impaired re-endothelialization after vascular injury |
(64) |
| C57BL/6 mice treated with agonist VUF11207 Reduced arterial thrombosis |
(66) |
| Vasculogenesis | |
| Conditional smooth muscle specific deficiency of Cxcl12 (SM22CRE-Cxcl12flox/flox
) Inhibition of ACKR3 expression which induces severe vascular defects |
(67) |
| Endothelial Ackr3-/- (Cxcr7flox/flox Cdh5-Cre) in hind-limb ischemia mice model Reduced blood flow recovery and vascular density in the ischemic gastrocnemius |
(64) |
| Cardioprotective effects | |
| Endothelial Ackr3-/- (Cxcr7flox/flox Cdh5-Cre)
Impaired cardiac function, reduced survival rate, increased infarct size and elevated plasma levels of CXCL12 |
(64) |
| Cardiomyocytes Ackr3-/-
(αMHC-Cre+/- CXCR7flox/flox) Excessive left ventricular dilatation and major systolic dysfunction after MI |
(68) |
| Fibroblasts Ackr3-/-
(Col1a2-CreERT2+/- CXCR7flox/flox) No significant impact on heart function under basal condition or after MI |
(68) |
| Conditional smooth muscle specific deficiency of Cxcl12 (SM22CRE-Cxcl12flox/flox
) treated with agonist TC14012 Reduced cardiac hypertrophy and attenuated vascular defects |
(67) |
| C57BL/6 mice overexpressing ACKR3 or treated with agonist TC14012 Improved heart function, reduced infarct size and enhanced angiogenesis after MI |
(64, 69) |
| C57BL/6 mice treated with agonist VUF11207 before MI Reduced thrombo-inflammatory response through modulation of the platelet lipidome, infarct size and improved cardiac function in a ischemia reperfusion mice model |
(66) |
| Silencing of Ackr3 (lentiviral shRNA) in C57BL/6 mice Inhibition of M1 macrophages polarization and reduction of inflammation post-MI |
(70) |
| Protective role in stroke | |
| C57BL/6 mice injected with anti-ACKR3 neutralizing antibody Enhanced neurogenesis in the hippocampal associated to cognitive functional recovery following cerebral ischemia |
(71) |