Ribosomal protein L13a deficiency in macrophages promotes atherosclerosis by limiting translation control-dependent retardation of inflammation

Abhijit Basu, Darshana Poddar, Peggy Robinet, Jonathan D. Smith, Maria Febbraio, William M. Baldwin, Barsanjit Mazumder

Research output: Contribution to journalArticle

Abstract

OBJECTIVE - : Unresolved inflammatory response of macrophages plays a pivotal role in the pathogenesis of atherosclerosis. Previously we showed that ribosomal protein L13a-dependent translational silencing suppresses the synthesis of a cohort of inflammatory proteins in monocytes and macrophages. We also found that genetic abrogation of L13a expression in macrophages significantly compromised the resolution of inflammation in a mouse model of lipopolysaccharide-induced endotoxemia. However, its function in the pathogenesis of atherosclerosis is not known. Here, we examine whether L13a in macrophage has a protective role against high-fat diet-induced atherosclerosis. APPROACH AND RESULTS - : We bred the macrophage-specific L13a knockout mice L13a Flox Cre onto apolipoprotein E-deficient background and generated the experimental double knockout mice L13a Flox Cre apolipoprotein E deficient (apoE). L13a Flox Cre mice on apolipoprotein E-deficient background were used as controls. Control and knockout mice were subjected to high-fat diet for 10 weeks. Evaluation of aortic sinus sections and entire aorta by en face showed significantly higher atherosclerosis in the knockout mice. Severity of atherosclerosis in knockout mice was accompanied by thinning of the smooth muscle cell layer in the media, larger macrophage area in the intimal plaque region and higher plasma levels of inflammatory cytokines. In addition, macrophages isolated from knockout mice had higher polyribosomal abundance of several target mRNAs, thus showing defect in translation control. CONCLUSIONS - : Our data demonstrate that loss of L13a in macrophages increases susceptibility to atherosclerosis in apolipoprotein E-deficient mice, revealing an important role of L13a-dependent translational control as an endogenous protection mechanism against atherosclerosis.

Original languageEnglish (US)
Pages (from-to)533-542
Number of pages10
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume34
Issue number3
DOIs
StatePublished - Mar 2014
Externally publishedYes

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Protein Deficiency
Ribosomal Proteins
Atherosclerosis
Knockout Mice
Macrophages
Inflammation
Apolipoproteins E
High Fat Diet
Tunica Intima
Macrophage Inflammatory Proteins
Sinus of Valsalva
Endotoxemia
Smooth Muscle Myocytes
Lipopolysaccharides
Aorta
Monocytes
Cytokines
Messenger RNA

Keywords

  • Atherosclerosis
  • Chemokines
  • Inflammation
  • Macrophages
  • Ribosomal protein L13a, mouse

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Ribosomal protein L13a deficiency in macrophages promotes atherosclerosis by limiting translation control-dependent retardation of inflammation. / Basu, Abhijit; Poddar, Darshana; Robinet, Peggy; Smith, Jonathan D.; Febbraio, Maria; Baldwin, William M.; Mazumder, Barsanjit.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 34, No. 3, 03.2014, p. 533-542.

Research output: Contribution to journalArticle

Basu, Abhijit ; Poddar, Darshana ; Robinet, Peggy ; Smith, Jonathan D. ; Febbraio, Maria ; Baldwin, William M. ; Mazumder, Barsanjit. / Ribosomal protein L13a deficiency in macrophages promotes atherosclerosis by limiting translation control-dependent retardation of inflammation. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2014 ; Vol. 34, No. 3. pp. 533-542.
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AU - Febbraio, Maria

AU - Baldwin, William M.

AU - Mazumder, Barsanjit

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AB - OBJECTIVE - : Unresolved inflammatory response of macrophages plays a pivotal role in the pathogenesis of atherosclerosis. Previously we showed that ribosomal protein L13a-dependent translational silencing suppresses the synthesis of a cohort of inflammatory proteins in monocytes and macrophages. We also found that genetic abrogation of L13a expression in macrophages significantly compromised the resolution of inflammation in a mouse model of lipopolysaccharide-induced endotoxemia. However, its function in the pathogenesis of atherosclerosis is not known. Here, we examine whether L13a in macrophage has a protective role against high-fat diet-induced atherosclerosis. APPROACH AND RESULTS - : We bred the macrophage-specific L13a knockout mice L13a Flox Cre onto apolipoprotein E-deficient background and generated the experimental double knockout mice L13a Flox Cre apolipoprotein E deficient (apoE). L13a Flox Cre mice on apolipoprotein E-deficient background were used as controls. Control and knockout mice were subjected to high-fat diet for 10 weeks. Evaluation of aortic sinus sections and entire aorta by en face showed significantly higher atherosclerosis in the knockout mice. Severity of atherosclerosis in knockout mice was accompanied by thinning of the smooth muscle cell layer in the media, larger macrophage area in the intimal plaque region and higher plasma levels of inflammatory cytokines. In addition, macrophages isolated from knockout mice had higher polyribosomal abundance of several target mRNAs, thus showing defect in translation control. CONCLUSIONS - : Our data demonstrate that loss of L13a in macrophages increases susceptibility to atherosclerosis in apolipoprotein E-deficient mice, revealing an important role of L13a-dependent translational control as an endogenous protection mechanism against atherosclerosis.

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