Community-based Statins and Advanced Carotid Plaque: Role of CD163 Positive Macrophages in Lipoprotein-associated Phospholipase A Activity in Atherosclerotic Plaque

Background And Aims: Lipoprotein-associated phospholipase A (Lp-PLA), an enzymatic inflammatory biomarker primarily bound to low-density lipoprotein cholesterol, is associated with an approximate twofold increased risk of cardiovascular disease and stroke. Despite indications that circulating Lp-PLA is sensitive to statins, it remains largely unknown whether statin usage exerts local effects on Lp-PLA expression at the site of atheromatous plaque.

Methods: Carotid plaques (n = 38) were prospectively collected from symptomatic (n = 18) and asymptomatic (n = 20) patients with (n = 20) or without (n = 18) documented statin history. In all cases, endarterectomy was performed where the primary stenosis was removed in an undisturbed manner. Serial cryosections of the presenting lesion were assessed histologically for macrophages, Lp-PLA, and cell death (apoptotic index).

Results: Symptomatic lesions exhibited less calcification, with greater inflammation characterized by increased expression of CD68 and CD163 macrophage subsets, and Lp-PLA. Symptomatic plaques also exhibited greater necrotic core area and increased apoptosis, as compared with asymptomatic lesions. In contrast, statin treatment did not appear to influence any of these parameters, except for the extent of apoptosis, which was less in statin treated as compared with statin naïve lesions. Overall, Lp-PLA expression correlated positively with necrotic core area, CD68 and CD163 macrophage area, and cell death. Finally, in vitro assays and dual immunofluorescence staining confirmed CD163-expressing monocytes/macrophages are also a major source of Lp-PLA.

Conclusions: Statin treatment has no effect on local atherosclerotic lesion Lp-PLA2 activity, therefore, the addition of anti-inflammatory treatments to further decrease macrophage Lp-PLA expression in atherosclerotic lesions may reduce lesional inflammation and cell death, and prevent necrotic core expansion and lesion progression.