MYD88 and Proinflammatory Chemokines in Aortic Atheromatosis: Exploring Novel Statin Effects

Abstract

Atherosclerosis is driven by a diverse range of cellular and molecular processes. In the present study, we sought to better understand how statins mitigate proatherogenic inflammation. 48 male New Zealand rabbits were divided into eight groups, each including 6 animals. The control groups received normal chow for 90 and 120 days. Three groups underwent a hypercholesterolemic diet (HCD) for 30, 60, and 90 days. Another three groups underwent HCD for 3 months, followed by normal chow for one month, with or without rosuvastatin or fluvastatin. The cytokine and chemokine expressions were assessed in the samples of thoracic and abdominal aorta. Rosuvastatin significantly reduced MYD88, CCL4, CCL20, CCR2, TNF-α, IFN-β, IL-1b, IL-2, IL-4, IL-8, and IL-10, both in the thoracic and abdominal aorta. Fluvastatin also downregulated MYD88, CCR2, IFN-β, IFN-γ, IL-1b, IL-2, IL-4, and IL-10 in both aortic segments. Rosuvastatin curtailed the expression of CCL4, IFN-β, IL-2, IL-4, and IL-10 more effectively than fluvastatin in both types of tissue. MYD88, TNF-α, IL-1b, and IL-8 showed a stronger downregulation with rosuvastatin compared to fluvastatin only in the thoracic aorta. The CCL20 and CCR2 levels reduced more extensively with rosuvastatin treatment only in abdominal aortic tissue. In conclusion, statin therapy can halt proatherogenic inflammation in hyperlipidemic animals. Rosuvastatin may be more effective in downregulating MYD88 in atherosclerotic thoracic aortas.

Keywords: CCL20; CCL4; CCR2; MYD88; atherosclerosis; statin.

Figure 1

Effects of a high-fat diet and statin treatment on the thoracic rabbit aorta. (a) MYD88; (b) NF-kB; (c) CCL4; (d) CCL20; (e) CCR2; (f) IFNβ; (g) IFNγ; (h) TNFα; (i) IL-1b; (j) IL-2; (k) IL-4; (l) IL-8; (m) IL-10; (n) IL-18. Significant difference (p < 0.05) versus C90 (*), C120 (#), G30 (a), G60 (b), G90 (c), G120 (d), and GF120 (e).

Figure 2

Effects of a high-fat diet and statin treatment on the abdominal rabbit aorta. (a) MYD88; (b) NF-kB; (c) CCL4; (d) CCL20; (e) CCR2; (f) IFNβ; (g) IFNγ; (h) TNFα; (i) IL-1b; (j) IL-2; (k) IL-4; (l) IL-8; (m) IL-10; (n) IL-18. Significant difference (p < 0.05) versus C90 (*), C120 (#), G30 (a), G60 (b), G90 (c), G120 (d), and GF120 (e).