Table 1.
Summary of selected studies investigating the role of CCL2 & CCR2 in cardiovascular diseases.
| Conditions | Experimental Model/Study population | Major findings related to CCL2/CCR2 axis | References | |
|---|---|---|---|---|
| Heart Failure | ||||
| CHF | Rats with ACF | CCL2 contributed to the progression of cardiac decompensation and the development of CHF | (8) | |
| Hypertensive heart disease | Rats with suprarenal aortic constriction | CCL2-mediated macrophage aggregation acted on myocardial fibrosis via a TGF-β-mediated process | (12) | |
| Genetic HF | Des-/- mice | Downregulation of CCR2, Arg1 and pro-fibrotic gene expression ameliorated poor cardiac remodeling, inflammation and failure | (13) | |
| End-stage HF | Hearts from patients with end-stage HF and in organ donors | First demonstrated the expression and protein localization of CCL2/CCR2 in human myocardium | (14) | |
| CHF | CHF patients | Serum CCL2 levels were positively related to the seriousness of symptoms as well as the degree of left heart insufficiency in patients with CHF | (15) | |
| Advanced HF | Advanced HF patients | CCL2 was significantly associated with poor prognosis in patients with advanced heart failure | (16) | |
| Atherosclerosis and coronary artery atherosclerotic heart disease | ||||
| Atherosclerosis | Rabbits with endothelial desiccation and atherogenic diet | CCL2-induced migration of monocytes to the vessel wall was a key activity contributing to the development of atherosclerosis | (17) | |
| Atherosclerosis | Diseased human arteries | CCL2 had a potential function in mediating mononuclear cell infiltration in the arterial wall | (18) | |
| Atherosclerosis | LDL-R-/-/CCL2-/- mice with high cholesterol diet | CCL2 played a specific and essential role in the activation of atherosclerosis | (19) | |
| Atherosclerosis | CCR2−/−, apoE−/− mice | Selective deletion of CCR2 significantly reduced lesion formation of apoE-/- mice | (20) | |
| Atherosclerosis | Human atherosclerotic plaque samples | CCL2 of human atherosclerotic plaques was significantly related to plaque vulnerability characteristics | (21) | |
| Stroke | Healthy adults | Genetic susceptibility to increased circulating CCL2 levels was related to a higher risk of stroke | (22) | |
| Atherosclerosis | ApoE-/- mice with MI | Monocyte-targeted RNAi with CCR2 as a target improved infarct healing in atherosclerosis-prone mice | (23) | |
| MI | CCL2-/- mice/CCL2 antibody neutralization mice with reperfused MI | CCL2 regulated inflammatory responses essential for MI repair | (24) | |
| MI | RAW 264.7 cells Mice with MI |
Lipid micelles loaded with CCR2 inhibitors affected inflammatory cell migration and cardiac function after MI | (25) | |
| Ischemic preconditioning | CCL2 TG mice with Coronary artery occlusion and reperfusion | Cardiac overexpression of CCL2 simulated ischemic preconditioning via the activation of SAPK/JNK1/2 | (26) | |
| MI | MHC/MCP-1 mice with MI | CCL2 overexpression in the heart prevented cardiac dysfunction and remodeling after MI | (27) | |
| Hypertension | ||||
| Hypertension | CCR2-deficient mice injected with Ang II | CCR2 was required for macrophage infiltration and vascular hypertrophy in ang II-induced hypertension | (10) | |
| Hypertension | CCR2-/-mice/BMT-CCR2-/- mice injected with Ang II | CCR2 played a key role in hypertension-induced vascular inflammation and remodeling | (28) | |
| Hypertension | RASMCs treated with Ang II | Ang II directly stimulated the expression of the CCL2 gene in the vascular system via the AT1 receptor | (29) | |
| Arterial hypertension | Caucasian patients with primary Arterial hypertension | CCL2 was observed to be increased in hypertensive patients and correlated with the extent of organ injury | (30) | |
| Salt-sensitive hypertension | TRPV1-/- mice receiving DOCA-salt with vehicle | Enhanced CCL2-CCR2 signaling pathway exacerbated renal injury in patients with salt-sensitive hypertension | (31) | |
| Renovascular hypertension | CCL2 KO mice with renal artery stenosis | CCL2 is a key mediator of chronic kidney injury in renovascular hypertension | (32) | |
| Salt-sensitive hypertension | Dahl SS rats with high salt diet | CCL2 mediated early renal leukocyte infiltration of salt-sensitive hypertension | (33) | |
| Myocardial disease | ||||
| EAM/Acute myocarditis | Rats injected with Porcine cardiac myosin Acute myocarditis patients |
CCL2 played a significant role in the progression of EAM in rats and in the pathogenesis of acute myocarditis in humans | (34) | |
| EAM | Rats injected with Porcine cardiac myosin | CCL2 promoted the migration and proliferation of monocytes/macrophages in EAM | (35) | |
| EAM | Mice injected with mixture of cardiac myosin polypeptide | The expression of CCL2 in EAM was upregulated by IL-17 through Act1/TRAF6/TAK1 | (36) | |
| Viral myocarditis | Mice infected with CVB3 | Blockade of CCL2 activity protected against CVB3-induced myocarditis by impairing Th1 polarization | (37) | |
| EAM | CCR2-/- mice injected with Murine cardiac myosin | The CCL2/CCR2 axis played an important role in the induction of EAM | (38) | |
| DCM | DCM patients with low to moderate impairment of left ventricular function/Patients with severe left ventricular dysfunction | CCL2 contributed to cardiomyocyte injury in DCM by regulating monocyte infiltration and activation | (39) | |
| DCM | Mice injected with DOX | CCR2 inhibition reduced mobilization of Ly6Chigh monocytes in bone marrow and improved cardiac inflammation and left ventricular dysfunction | (40) | |
| HCM | HCM patients | CCL2 was correlated with left ventricular systolic dysfunction in HCM patients and may be involved in its pathogenesis | (41) | |
| AC | Dsg2MT mice Dsg2cKO mice |
CCL2/CCR2 was involved in the regulation of inflammatory and repair processes during the progression of AC | (42) | |