CCL7 as a novel inflammatory mediator in cardiovascular disease, diabetes mellitus, and kidney disease

Abstract

Chemokines are key components in the pathology of chronic diseases. Chemokine CC motif ligand 7 (CCL7) is believed to be associated with cardiovascular disease, diabetes mellitus, and kidney disease. CCL7 may play a role in inflammatory events by attracting macrophages and monocytes to further amplify inflammatory processes and contribute to disease progression. However, CCL7-specific pathological signaling pathways need to be further confirmed in these chronic diseases. Given the multiple redundancy system among chemokines and their receptors, further experimental and clinical studies are needed to clarify whether direct CCL7 inhibition mechanisms could be a promising therapeutic approach to attenuating the development of cardiovascular disease, diabetes mellitus, and kidney disease.

Keywords: Cardiovascular disease; Chemokine; Chemokine CC motif ligand 7; Chronic kidney disease; Diabetes mellitus; Diabetic kidney disease.

Fig. 1

The correlation of CCL7 in cardiovascular disease, diabetes mellitus, and kidney disease in this review article. CCL7 can be induced in endothelial cells, VSMCs, and THP-1 under the stimulation of PMA, TNF-α or LPS. CCR1, CCR2, CCR3 and CCR5 are the functional receptor of CCL7. CCL7 can recruit immune cells that express associated receptors, which may result in inflammatory related disease, such as cardiovascular disease, diabetes mellitus, and kidney disease. CCR1: CC chemokine receptor 1; CCR2: CC chemokine receptor 2; CCR3: CC chemokine receptor 3; CCR5: CC chemokine receptor 5; ERK: extracellular signal-regulated kinases; ESRD: end-stage renal disease; iNOS: inducible nitric oxide synthase; IL-6: interleukin-6; IL-12A/B: interleukin-12A/B; JAK2: Janus kinase 2; LPS: lipopolysaccharides; MAPK: mitogen-activated protein kinases; PI3K: phosphoinositide 3-kinases; PMA: phorbol 12-myristate 13-acetate; STAT1: signal transducer and activator of transcription 1; THP-1: myelomonocytic cells; TNF-α: tumor necrosis factor-alpha; VSMCs: vascular smooth muscle cells