A salmon protein hydrolysate exerts lipid-independent anti-atherosclerotic activity in ApoE-deficient mice - PubMed (original) (raw)

. 2014 May 19;9(5):e97598.

doi: 10.1371/journal.pone.0097598. eCollection 2014.

Rita Vik 2, Marco Busnelli 1, Bodil Bjørndal 2, Sverre Holm 3, Trond Brattelid 4, Stefano Manzini 1, Giulia S Ganzetti 1, Federica Dellera 1, Bente Halvorsen 3, Pål Aukrust 3, Cesare R Sirtori 1, Jan E Nordrehaug 5, Jon Skorve 2, Rolf K Berge 6, Giulia Chiesa 1

Affiliations

A salmon protein hydrolysate exerts lipid-independent anti-atherosclerotic activity in ApoE-deficient mice

Cinzia Parolini et al. PLoS One. 2014.

Abstract

Fish consumption is considered health beneficial as it decreases cardiovascular disease (CVD)-risk through effects on plasma lipids and inflammation. We investigated a salmon protein hydrolysate (SPH) that is hypothesized to influence lipid metabolism and to have anti-atherosclerotic and anti-inflammatory properties. 24 female apolipoprotein (apo) E(-/-) mice were divided into two groups and fed a high-fat diet with or without 5% (w/w) SPH for 12 weeks. The atherosclerotic plaque area in aortic sinus and arch, plasma lipid profile, fatty acid composition, hepatic enzyme activities and gene expression were determined. A significantly reduced atherosclerotic plaque area in the aortic arch and aortic sinus was found in the 12 apoE(-/)- mice fed 5% SPH for 12 weeks compared to the 12 casein-fed control mice. Immunohistochemical characterization of atherosclerotic lesions in aortic sinus displayed no differences in plaque composition between mice fed SPH compared to controls. However, reduced mRNA level of Icam1 in the aortic arch was found. The plasma content of arachidonic acid (C20:4n-6) and oleic acid (C18:1n-9) were increased and decreased, respectively. SPH-feeding decreased the plasma concentration of IL-1β, IL-6, TNF-α and GM-CSF, whereas plasma cholesterol and triacylglycerols (TAG) were unchanged, accompanied by unchanged mitochondrial fatty acid oxidation and acyl-CoA:cholesterol acyltransferase (ACAT)-activity. These data show that a 5% (w/w) SPH diet reduces atherosclerosis in apoE(-/-) mice and attenuate risk factors related to atherosclerotic disorders by acting both at vascular and systemic levels, and not directly related to changes in plasma lipids or fatty acids.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1

Figure 1. Atherosclerotic plaque level in apoE−/− mice fed a high-fat diet (control) or a diet with 5% SPH.

After 12 weeks of dietary treatment, whole aorta was collected and en-face analysis was performed to quantify aortic surface covered by atherosclerotic plaques. Bars represent means ± SD of 12 mice for each diet. Unpaired _t_-test was used to detect statistical significance (*P<0.05).

Figure 2

Figure 2. Histological and immunohistochemical characterization of plaques in the aortic sinus in apoE−/− mice fed a high-fat diet (control) or a diet with 5% SPH for 12 weeks.

Representative photomicrographs and quantification of maximum plaque area (panels A–C). Representative photomicrographs and quantification of extracellular matrix deposition (panels D–F), Lipid deposition (panels G–I), Macrophages (panels J–L) and T lymphocytes (panels M–O). The amount of extracellular matrix, lipids, macrophages and T-lymphocytes is expressed as percentage of the stained area over the total plaque area. Bar in panel A = 100 µm. Positive area (%) refers to the percentage of the plaque area occupied by connective tissue, lipids, macrophages and T lymphocytes, respectively. Data are shown as means ± SD for 6 mice for each diet and unpaired _t_-test was used to detect significance (*P<0.05).

Figure 3

Figure 3. Levels of mRNA expression in aorta and inflammatory mediators in plasma in apoE−/− mice fed a high-fat diet (control) or a diet with 5% SPH for 12 weeks.

(A) The gene expressions of the inflammatory markers Icam1, Vcam1, Nos2 and Mcp1 were measured in pooled aortic arch from six mice. Inflammatory markers in blood samples collected at day 77 of treatment were analysed (B) IL-1β, (C) IL-6, (D) IL-10, (E) TNF-α, (F) GM-CSF and bars represent means ± SD of 4 pooled samples of 3 mice for each diet. Unpaired _t_-test was used to assess statistical significance and results significantly different from control are indicated (*P<0.05, **P<0.01).

Figure 4

Figure 4. Hepatic gene expression in apoE−/− mice fed a high-fat diet (control) or a diet with 5% SPH for 12 weeks.

Hepatic mRNA levels of (A) Acaca and (B) Scd1. Data for gene expressions are shown as mean values relative to control ± SD for 4 mice for each diet. Mann-Whitney test was used to assess statistical significance (*P<0.05).

References

    1. Lloyd-Jones DM (2010) Cardiovascular risk prediction: basic concepts, current status, and future directions. Circulation 121: 1768–1777. - PubMed
    1. Woollard KJ (2013) Immunological aspects of atherosclerosis. Clinical Science 125: 221–235. - PubMed
    1. Hansson GK, Robertson A-KL, Söderberg-Nauclér C (2006) Inflammation and atherosclerosis annual review of pathology: Mechanisms of disease. Annual Reviews 1 297–329. - PubMed
    1. van der Wal AC, Becker AE, van der Loos CM, Das PK (1994) Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology. Circulation 89: 36–44. - PubMed
    1. Sabesin SM (1981) Lipid and lipoprotein abnormalities in alcoholic liver disease. Circulation 64: III 72–84. - PubMed

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