FFAR4 Deficiency Increases Necrotic Cores in Advanced Lesions of ApoE-/- Mice-Brief Report. Arterioscler Thromb Vasc Biol 2025 May;45(5):675-682
Date
03/06/2025Pubmed ID
40047073Pubmed Central ID
PMC12018153DOI
10.1161/ATVBAHA.124.322371Scopus ID
2-s2.0-86000592687 (requires institutional sign-in at Scopus site) 1 CitationAbstract
BACKGROUND: FFAR4 (free fatty acid receptor 4) has emerged as a target for preventing cardiovascular disease through its ability to control macrophage inflammation and foam cell formation. Previous studies have shown that FFAR4 activation can protect against the accumulation of arterial plaque buildup in atherosclerotic animal models. The goal of our study is to test the hypothesis that FFAR4 deficiency will increase atherosclerotic plaque development in apoE-/- mice.
METHODS: Male and female apoE-/-/Ffar4-/- mice and their apoE-/- controls were fed a Western diet for 8 or 16 weeks to assess early and advanced atherosclerotic lesions, respectively. At the end of each study, atherosclerotic plaque severity was determined by analyzing the aortic sinus lesion area of the heart and the en face lesion area of the aortic arch.
RESULTS: Following 8 weeks of Western diet feeding, lesions from apoE-/-/Ffar4-/- male and female mice had 33% and 22% decreases, respectively, in the aortic sinus lesion area with no changes in the aortic arch lesion area. After 16 weeks of Western diet feeding, the lesions showed no changes in the area or volume of the aortic sinus between apoE-/-/Ffar4-/- mice and apoE-/- controls. However, male apoE-/-/Ffar4-/- mice had a 27% increase in the plaque lesion area in the aortic arch compared with apoE-/- controls. Despite similar sizes of lesions in the aortic sinus, apoE-/-/Ffar4-/- mice had larger necrotic cores compared with the apoE-/- control mice. In fact, male and female mice had 43% and 37% increases in the necrotic lesion area, respectively.
CONCLUSIONS: These data suggest a novel role for FFAR4 in reducing necrotic core lesion formation and support a protective role for FFAR4 in stabilizing atherosclerotic plaques.
Author List
Stuttgen GM, Bobek JM, Penoske R, Wadding-Lee C, Lam M, Hader SN, Owens AP 3rd, Sahoo DAuthor
Daisy Sahoo PhD Dean, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAorta, Thoracic
Aortic Diseases
Apolipoproteins E
Atherosclerosis
Diet, Western
Disease Models, Animal
Female
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Knockout, ApoE
Necrosis
Plaque, Atherosclerotic
Receptors, G-Protein-Coupled
Severity of Illness Index
Sinus of Valsalva
