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C–C motif chemokine ligand 2 (CCL2) is a pro-inflammatory chemokine important for monocyte recruitment to the arterial wall and atherosclerotic plaques. Global knockout of Ccl2reduces plaque formation and macrophage content in mice, but the importance of different plaque cell types in mediating this effect has not been resolved. Smooth muscle cells (SMCs) can adopt a potentially pro-inflammatory function with expression of CCL2. The present study aimed to test the hypothesis that SMC-secreted CCL2 is involved in early atherogenesis in mice.

Lipoprotein-proteoglycan binding is an early key event in atherosclerotic lesion formation, and thus conceivably could play a major role in vasculopathy-driven chronic graft failure and cardiovascular mortality in renal transplant recipients. The present study investigated whether lipoprotein-proteoglycan binding susceptibility (LPBS) of apolipoprotein B-containing lipoproteins and levels of the classical atherosclerosis biomarker low-density lipoprotein cholesterol (LDL-C) were associated with cardiovascular mortality (n=130) and graft failure (n=73) in 589 renal transplant recipients who were followed from at least 1-year post-transplantation for 9.5 years. At baseline, LPBS was significantly higher in patients who subsequently developed graft failure compared to those with a surviving graft (1.68 ± 0.93 versus 1.46 ± 0.49 nmol/mmol, p = 0.001). Cox regression analysis showed an association between LPBS and chronic graft failure in an age- and sex-adjusted model (hazard ratio: 1.45; 95% CI, 1.14-1.85; p = 0.002), but no association was observed with cardiovascular mortality. LDL-C levels were not associated with graft failure, nor with cardiovascular mortality. This study shows that measurement of cholesterol retention outperformed the traditionally-used quantitative parameter of LDL cholesterol levels in predicting graft failure, suggesting a higher relevance of pro-atherogenic function compared to quantity of apolipoprotein B-containing lipoproteins in chronic graft failure.