Lps-Induced Systemic Inflammation does not Alter Atherosclerotic Plaque Area or Inflammation in Apoe3*Leiden Mice in the Early Phase Up to 15 Days

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Abstract

Background and aims:

Observational studies show a peak incidence in cardiovascular events during and early after clinical conditions associated with substantial systemic inflammation, such as pneumonia. The acuteness of this increased risk suggests rapid plaque destabilization and associated intra-plaque inflammation. We evaluated whether LPS-evoked acute systemic inflammation would induce such detrimental vascular changes in murine aortas with manifest atherosclerotic lesions.

Methods and results:

ApoE3*Leiden mice were fed a high cholesterol diet for 20 weeks to establish atherosclerosis. Thereafter, mice received a single intraperitoneal injection with lipopolysaccharides (LPS) to induce systemic inflammation, or saline for control. Mice were sacrificed 2 or 15 days post-LPS injection (n = 17) or post-saline injection (n = 13). Serum amyloid A (SAA), a sensitive marker of systemic inflammation, increased 250-fold in LPS-treated mice. Aortic root plaques were assessed for total plaque area, plaque severity and inflammatory cell content. No significant differences in total surface area of atherosclerotic plaque were found between control and LPS groups sacrificed after 2 days (resp. 0.409 ± 0.228 x 105 μm2 vs. 0.285 ± 0.169 x 105 μm2) (p = 0.31), and 15 days (resp. 0.950 ± 0.938 x 105 μm2 vs. 0.612 ± 0.413 x 105 μm2) (p = 0.80). Furthermore, plaque type and number of lesions were unaltered and intra-plaque density of macrophages and lymphocytes were comparable in both groups.

Conclusions:

Intraperitoneal LPS injection in ApoE3*Leiden mice triggers a profound systemic inflammatory response, but does not increase atherosclerotic plaque area or inflammatory cell density. This model of LPS-induced inflammation in atherosclerosis-prone mice argues against intra-plaque alterations as an explanation for acute inflammation-induced cardiovascular event risk.

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