Wessel W Fuijkschot1,2,3, Martine C Morrison4, Ilse P A Zethof1, Paul A J Krijnen1,2, Robert Kleemann4, Hans W M Niessen1,2,5, Yvo M Smulders2,3. 1. Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. 2. Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, Amsterdam, The Netherlands. 3. Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands. 4. Department of Metabolic Health Research, The Netherlands Organization for Applied Scientific Research (TNO), Leiden, The Netherlands. 5. Department of Cardiac Surgery, VU University Medical Center, Amsterdam, The Netherlands.
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 intraplaque inflammation. We evaluated whether lipopolysaccharides (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 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, 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 × 10 μm vs. 0.285 ± 0.169 × 10 μm) (P = 0.31), and 15 days (resp. 0.950 ± 0.938 × 10 μm vs. 0.612 ± 0.413 × 10 μm) (P = 0.80). Furthermore, plaque type and number of lesions were unaltered and intraplaque density of macrophages and lymphocytes were comparable in both the 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 intraplaque alterations as an explanation for acute inflammation-induced cardiovascular event risk.
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 intraplaque inflammation. We evaluated whether lipopolysaccharides (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 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, 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 × 10 μm vs. 0.285 ± 0.169 × 10 μm) (P = 0.31), and 15 days (resp. 0.950 ± 0.938 × 10 μm vs. 0.612 ± 0.413 × 10 μm) (P = 0.80). Furthermore, plaque type and number of lesions were unaltered and intraplaque density of macrophages and lymphocytes were comparable in both the 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 intraplaque alterations as an explanation for acute inflammation-induced cardiovascular event risk.
Authors: Andrea Piccioni; Tommaso de Cunzo; Federico Valletta; Marcello Covino; Emanuele Rinninella; Pauline Raoul; Christian Zanza; Maria Cristina Mele; Francesco Franceschi Journal: Int J Environ Res Public Health Date: 2021-04-16 Impact factor: 3.390