Role of methylene blue dye in sentinel node biopsy in N0 oral cavity squamous cell carcinoma.

BACKGROUND: Presence of neck nodes in cases of head neck squamous cell cancers is an adverse prognostic factor. Elective neck dissection is traditionally recommended along with primary disease resection. Sentinel lymph node (SLN) is the first draining node. Sentinel lymph node biopsy (SNB) is a minimally invasive technique to identify occult nodal metastasis in early HNSCC. METHODS: The objective of this study is to determine the identification rate of SNB using methylene blue dye (MBD) in N0 neck of Oral Squamous cell carcinoma (OSCC) and estimating specificity, sensitivity, negative predictive value and positive predictive value of SNB with frozen section (FS) analysis and in comparison to post-operative histopathological examination (HPE). It is a cross-sectional study conducted at a tertiary care centre, Lucknow, India. 21 patients of N0 OSCC from January 2019 to May 2020, were included. All patients underwent peritumoral injection with MBD. Sentinel nodes were harvested and sent for FS. Depending on FS findings, appropriate neck dissection was performed. RESULTS: SLN was identified at level Ib and II in 19 patients (90.47%). The sensitivity, specificity, PPV and NPV in identifying SLN using MBD versus FS were 100.00%, 11.11%, 15.79% and 100.00% respectively. Whereas, SLN using MBD versus HPE specimens were 100.00%, 10.52%, 10.52% and 100.00% respectively. CONCLUSION: Despite having 100% sensitivity, MBD alone has poor specificity. With this poor discriminatory power, it is unlikely to be employed as a diagnostic test alone. It is recommended to rely on per-operative FS for taking decision as far as extent of neck dissection in N0 neck is concerned.

Evaluation of Eustachian Tube Function in Cases of Chronic Otitis Media by Dynamic Slow Motion Videoendoscopy and Impedance Audiometry.

Eustachian tube (ET) dysfunction is known to be a cause for various middle ear diseases. Dynamic slow motion videoendoscopy (DSVE) and impedance audiometry (IA) can both be employed to evaluate ET dysfunction. To assess the role of DSVE and IA for diagnosing ET dysfunction in cases of middle ear disorders. It is a prospective case control study. 102 ears with chronic otitis media were taken as cases and 102 healthy ears as controls. IA and DSVE were performed to assess ET function in both the groups. Sensitivity/ specificity of both the diagnostic tests were evaluated in case and control groups. Out of 102 ET of case group exposed to both tests, 87 were found to have ET dysfunction by DSVE and 80 by IA. Among 102 ET of control group 78 were identified as normal by DSVE while 87 by IA. On applying chi square test in both these groups, the associations were significant. (p value < 0.0001). Patients with grade 2B or higher on DSVE endoscopy had abnormal IA findings, indicating that higher the grade on DSVE, higher the chance of abnormal IA. DSVE and IA are potentially useful tools in evaluation of cases of COM and which provide information regarding functional and pathological factors responsible for ET dysfunction.

3, 3'- (3, 5-DCPBC) Down-Regulates Multiple Phosphokinase Dependent Signal Transduction Pathways in Malignant Melanoma Cells through Specific Diminution of EGFRY1086 Phosphorylation.

Melanoma is the most dangerous skin malignancy due to its strong metastatic potential with high mortality. Activation of crucial signaling pathways enforcing melanoma progression depends on phosphorylation of distinct tyrosine kinases and oxidative stress. We here investigated the effect of a bis-coumarin derivative [3, 3'- ((3″, 5'-Dichlorophenyl) methylene) bis (4-hydroxy-2H-chromen-2-one)] [3, 3'- (3, 5-DCPBC)] on human melanoma cell survival, growth, proliferation, migration, intracellular redox state, and deciphered associated signaling pathways. This derivative is toxic for melanoma cells and non-toxic for melanocytes, their benign counterpart, and fibroblasts. 3, 3'- (3, 5-DCPBC) inhibits cell survival, migration, and proliferation of different metastatic and non-metastatic melanoma cell lines through profound suppression of the phosphorylation of Epidermal Growth Factor receptor (EGFR) and proto-oncogene cellular sarcoma (c-SRC) related downstream pathways. Thus, 3, 3'- (3, 5-DCPBC) endowed with the unique property to simultaneously suppress phosphorylation of multiple downstream kinases, such as EGFR/JAK/STAT and EGFR/SRC and their corresponding transcription factors.

Role of Octreotide in Conservative Management of Chyle Leak Post Neck Dissection in Cases of Head Neck Cancer: A Retrospective Analysis.

Chyle leak is a dreadful complication in patients undergoing neck dissections. Octreotide has been used in the management of chyle leak post neck dissections in head and neck cancer patients. Currently there is no consensus and practice guidelines on the same. (1) To study the role of octreotide in early cessation of post neck dissection chyle leak. (2) To study incidence of intra-operative and post-operative CL, its relation to the extent of nodal disease and neck dissection, prior radiotherapy. Retrospective analysis of 16 patients out of 529 neck dissection over a period of 03 years between Jan 2016 and Dec 2019 who developed post-operative chyle leak. All patients who had post-operative chyle leak were administered octreotide. Time taken for chyle leak to stop was primary outcome. Secondary outcomes were duration of hospitalization post-operatively, incidence of intra-operative and post-operative chyle leak, its relation to the extent of nodal disease, prior radiotherapy and type of neck dissection. 59 of 529 neck dissections (11.15%) were noted to have intra-operative chyle leak. 16 of 529 neck dissections (3.02%) developed post-operative chyle leak. On applying chi square test, prior multimodality and N plus neck were found to be significant risk factors in developing postoperative chyle leak. Considering only RT versus no RT in prior multimodality treated group, the difference was insignificant. Onset of chyle leak varied from 1 to 5 post-op day (mean 2.68 days). 15 (93.75%) patients responded to octreotide. Chyle leak resolved between 3 and 10 days (mean 5.18 days) and octreotide was given for 5-12 days (mean-7.18 days). Overall duration of hospitalization ranged from 09 to 18 days (mean 12.18 days). 01 patient (6.25%) had to be re-explored due to high volume leak despite using octreotide. Adverse effects of octreotide were minimal and tolerable. Octreotide is effective in reducing the duration of chyle leak, hospital stay and need for surgical intervention. It may be considered as suitable adjunct to conservative measures in the management for post-operative chyle leak.

A Systematic Review on Tracheostomy in COVID-19 Patients: Current Guidelines and Safety Measures.

At this moment the world is fighting with COVID-19 pandemic. Because of increasing number of critical cases, the ICU admissions are also increasing and overwhelming the hospital. These group of patients often required Tracheostomy for proper management and ventilation. As Surgeons we often required to examine and perform procedures in head and neck patients and are in high risk of exposure to aerosol and droplet contamination. We did a literature search for research regarding tracheostomy and its post procedure care during the ongoing COVID-19 pandemic. In this review various international guidelines and sources were put together, and we aim to summarize in a systematic way the available recommendations: indications, timing, technique and safety measures for tracheostomy for COVID-19 patients, from all over the world.

A Structurally Conserved RNA Element within SARS-CoV-2 ORF1a RNA and S mRNA Regulates Translation in Response to Viral S Protein-Induced Signaling in Human Lung Cells.

The positive-sense, single-stranded RNA genome SARS-CoV-2 harbors functionally important cis-acting elements governing critical aspects of viral gene expression. However, insights on how these elements sense various signals from the host cell and regulate viral protein synthesis are lacking. Here, we identified two novel cis-regulatory elements in SARS-CoV-2 ORF1a and S RNAs and describe their role in translational control of SARS-CoV-2. These elements are sequence-unrelated but form conserved hairpin structures (validated by NMR) resembling gamma activated inhibitor of translation (GAIT) elements that are found in a cohort of human mRNAs directing translational suppression in myeloid cells in response to IFN-γ. Our studies show that treatment of human lung cells with receptor-binding S1 subunit, S protein pseudotyped lentivirus, and S protein-containing virus-like particles triggers a signaling pathway involving DAP-kinase1 that leads to phosphorylation and release of the ribosomal protein L13a from the large ribosomal subunit. Released L13a forms a virus activated inhibitor of translation (VAIT) complex that binds to ORF1a and S VAIT elements, causing translational silencing. Translational silencing requires extracellular S protein (and its interaction with host ACE2 receptor), but not its intracellular synthesis. RNA-protein interaction analyses and in vitro translation experiments showed that GAIT and VAIT elements do not compete with each other, highlighting differences between the two pathways. Sequence alignments of SARS-CoV-2 genomes showed a high level of conservation of VAIT elements, suggesting their functional importance. This VAIT-mediated translational control mechanism of SARS-CoV-2 may provide novel targets for small molecule intervention and/or facilitate development of more effective mRNA vaccines. IMPORTANCE Specific RNA elements in the genomes of RNA viruses play important roles in host-virus interaction. For SARS-CoV-2, the mechanistic insights on how these RNA elements could sense the signals from the host cell are lacking. Here we report a novel relationship between the GAIT-like SARS-CoV-2 RNA element (called VAITs) and the signal generated from the host cell. We show that for SARS-CoV-2, the interaction of spike protein with ACE2 not only serves the purpose for viral entry into the host cell, but also transduces signals that culminate into the phosphorylation and the release of L13a from the large ribosomal subunit. We also show that this event leads to the translational arrest of ORF1a and S mRNAs in a manner dependent on the structure of the RNA elements. Translational control of viral mRNA by a host-cell generated signal triggered by viral protein is a new paradigm in the host-virus relationship.

Angiogenin Released from ABCB5+ Stromal Precursors Improves Healing of Diabetic Wounds by Promoting Angiogenesis.

Severe angiopathy is a major driver for diabetes-associated secondary complications. Knowledge on the underlying mechanisms essential for advanced therapies to attenuate these pathologies is limited. Injection of ABCB5+ stromal precursors at the edge of nonhealing diabetic wounds in a murine db/db model, closely mirroring human type 2 diabetes, profoundly accelerates wound closure. Strikingly, enhanced angiogenesis was substantially enforced by the release of the ribonuclease angiogenin from ABCB5+ stromal precursors. This compensates for the profoundly reduced angiogenin expression in nontreated murine chronic diabetic wounds. Silencing of angiogenin in ABCB5+ stromal precursors before injection significantly reduced angiogenesis and delayed wound closure in diabetic db/db mice, implying an unprecedented key role for angiogenin in tissue regeneration in diabetes. These data hold significant promise for further refining stromal precursors-based therapies of nonhealing diabetic foot ulcers and other pathologies with impaired angiogenesis.

High-fat diet-induced GAIT element-mediated translational silencing of mRNAs encoding inflammatory proteins in macrophage protects against atherosclerosis.

Previously, we identified a mechanism of inflammation control directed by ribosomal protein L13a and "GAIT" (Gamma Activated Inhibitor of Translation) elements in target mRNAs and showed that its elimination in myeloid cell-specific L13a knockout mice (L13a KO) increased atherosclerosis susceptibility and severity. Here, we investigated the mechanistic basis of this endogenous defense against atherosclerosis. We compared molecular and cellular aspects of atherosclerosis in high-fat diet (HFD)-fed L13a KO and intact (control) mice. HFD treatment of control mice induced release of L13a from 60S ribosome, formation of RNA-binding complex, and subsequent GAIT element-mediated translational silencing. Atherosclerotic plaques from HFD-treated KO mice showed increased infiltration of M1 type inflammatory macrophages. Macrophages from KO mice showed increased phagocytic activity and elevated expression of LDL receptor and pro-inflammatory mediators. NanoString analysis of the plaques from KO mice showed upregulation of a number of mRNAs encoding inflammatory proteins. Bioinformatics analysis suggests the presence of the potential GAIT elements in the 3'UTRs of several of these mRNAs. Macrophage induces L13a/GAIT-dependent translational silencing of inflammatory genes in response to HFD as an endogenous defense against atherosclerosis in ApoE-/- model.

TLR4-dependent shaping of the wound site by MSCs accelerates wound healing.

We here address the question whether the unique capacity of mesenchymal stem cells to re-establish tissue homeostasis depends on their potential to sense pathogen-associated molecular pattern and, in consequence, mount an adaptive response in the interest of tissue repair. After injection of MSCs primed with the bacterial wall component LPS into murine wounds, an unexpected acceleration of healing occurs, clearly exceeding that of non-primed MSCs. This correlates with a fundamental reprogramming of the transcriptome in LPS-treated MSCs as deduced from RNAseq analysis and its validation. A network of genes mediating the adaptive response through the Toll-like receptor 4 (TLR4) pathway responsible for neutrophil and macrophage recruitment and their activation profoundly contributes to enhanced wound healing. In fact, injection of LPS-primed MSCs silenced for TLR4 fails to accelerate wound healing. These unprecedented findings hold substantial promise to refine current MSC-based therapies for difficult-to-treat wounds.

JunB defines functional and structural integrity of the epidermo-pilosebaceous unit in the skin.

Transcription factors ensure skin homeostasis via tight regulation of distinct resident stem cells. Here we report that JunB, a member of the AP-1 transcription factor family, regulates epidermal stem cells and sebaceous glands through balancing proliferation and differentiation of progenitors and by suppressing lineage infidelity. JunB deficiency in basal progenitors results in a dermatitis-like syndrome resembling seborrheic dermatitis harboring structurally and functionally impaired sebaceous glands with a globally altered lipid profile. A fate switch occurs in a subset of JunB deficient epidermal progenitors during wound healing resulting in de novo formation of sebaceous glands. Dysregulated Notch signaling is identified to be causal for this phenotype. In fact, pharmacological inhibition of Notch signaling can efficiently restore the lineage drift, impaired epidermal differentiation and disrupted barrier function in JunB conditional knockout mice. These findings define an unprecedented role for JunB in epidermal-pilosebaceous stem cell homeostasis and its pathology.

Author Correction: A Novel S100A8/A9 Induced Fingerprint of Mesenchymal Stem Cells associated with Enhanced Wound Healing.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

A Novel S100A8/A9 Induced Fingerprint of Mesenchymal Stem Cells associated with Enhanced Wound Healing.

We here investigated whether the unique capacity of mesenchymal stem cells (MSCs) to re-establish tissue homeostasis depends on their potential to sense danger associated molecular pattern (DAMP) and to mount an adaptive response in the interest of tissue repair. Unexpectedly, after injection of MSCs which had been pretreated with the calcium-binding DAMP protein S100A8/A9 into murine full-thickness wounds, we observed a significant acceleration of healing even exceeding that of non-treated MSCs. This correlates with a fundamental reprogramming of the transcriptome in S100A8/A9 treated MSCs as deduced from RNA-seq analysis and its validation. A network of genes involved in proteolysis, macrophage phagocytosis, and inflammation control profoundly contribute to the clean-up of the wound site. In parallel, miR582-5p and genes boosting energy and encoding specific extracellular matrix proteins are reminiscent of scar-reduced tissue repair. This unprecedented finding holds substantial promise to refine current MSC-based therapies for difficult-to-treat wounds and fibrotic conditions.

Conserved structures formed by heterogeneous RNA sequences drive silencing of an inflammation responsive post-transcriptional operon.

RNA-protein interactions with physiological outcomes usually rely on conserved sequences within the RNA element. By contrast, activity of the diverse gamma-interferon-activated inhibitor of translation (GAIT)-elements relies on the conserved RNA folding motifs rather than the conserved sequence motifs. These elements drive the translational silencing of a group of chemokine (CC/CXC) and chemokine receptor (CCR) mRNAs, thereby helping to resolve physiological inflammation. Despite sequence dissimilarity, these RNA elements adopt common secondary structures (as revealed by 2D-1H NMR spectroscopy), providing a basis for their interaction with the RNA-binding GAIT complex. However, many of these elements (e.g. those derived from CCL22, CXCL13, CCR4 and ceruloplasmin (Cp) mRNAs) have substantially different affinities for GAIT complex binding. Toeprinting analysis shows that different positions within the overall conserved GAIT element structure contribute to differential affinities of the GAIT protein complex towards the elements. Thus, heterogeneity of GAIT elements may provide hierarchical fine-tuning of the resolution of inflammation.

Alpha-Ketoglutarate Curbs Differentiation and Induces Cell Death in Mesenchymal Stromal Precursors with Mitochondrial Dysfunction.

Increased concentrations of reactive oxygen species (ROS) originating from dysfunctional mitochondria contribute to diverse aging-related degenerative disorders. But so far little is known about the impact of distinct ROS on metabolism and fate of stromal precursor cells. Here, we demonstrate that an increase in superoxide anion radicals due to superoxide dismutase 2 (Sod2) deficiency in stromal precursor cells suppress osteogenic and adipogenic differentiation through fundamental changes in the global metabolite landscape. Our data identify impairment of the pyruvate and l-glutamine metabolism causing toxic accumulation of alpha-ketoglutarate in the Sod2-deficient and intrinsically aged stromal precursor cells as a major cause for their reduced lineage differentiation. Alpha-ketoglutarate accumulation led to enhanced nucleocytoplasmic vacuolation and chromatin condensation-mediated cell death in Sod2-deficient stromal precursor cells as a consequence of DNA damage, Hif-1α instability, and reduced histone H3 (Lys27) acetylation. These findings hold promise for prevention and treatment of mitochondrial disorders commonly associated with aged individuals. Stem Cells 2017;35:1704-1718.

Senescent fibroblast-derived Chemerin promotes squamous cell carcinoma migration.

Aging is associated with a rising incidence of cutaneous squamous cell carcinoma (cSCC), an aggressive skin cancer with the potential for local invasion and metastasis. Acquisition of a senescence-associated secretory phenotype (SASP) in dermal fibroblasts has been postulated to promote skin cancer progression in elderly individuals. The underlying molecular mechanisms are largely unexplored. We show that Chemerin, a previously unreported SASP factor released from senescent human dermal fibroblasts, promotes cSCC cell migration, a key feature driving tumor progression. Whereas the Chemerin abundance is downregulated in malignant cSCC cells, increased Chemerin transcripts and protein concentrations are detected in replicative senescent fibroblasts in vitro and in the fibroblast of skin sections from old donors, indicating that a Chemerin gradient is built up in the dermis of elderly. Using Transwell® migration assays, we show that Chemerin enhances the chemotaxis of different cSCC cell lines. Notably, the Chemerin receptor CCRL2 is remarkably upregulated in cSCC cell lines and human patient biopsies. Silencing Chemerin in senescent fibroblasts or the CCRL2 and GPR1 receptors in the SCL-1 cSCC cell line abrogates the Chemerin-mediated chemotaxis. Chemerin triggers the MAPK cascade via JNK and ERK1 activation, whereby the inhibition impairs the SASP- or Chemerin-mediated cSCC cell migration.Taken together, we uncover a key role for Chemerin, as a major factor in the secretome of senescent fibroblasts, promoting cSCC cell migration and possibly progression, relaying its signals through CCRL2 and GPR1 receptors with subsequent MAPK activation. These findings might have implications for targeted therapeutic interventions in elderly patients.

Hyperuricaemia - A Potential Indicator to Diagnose the Risk of Essential Hypertension.

INTRODUCTION: Hypertension has turned out to be the major cause of morbidity among the life style diseases. Studies in human and animal models have documented an independent association of hyperuricaemia with early hypertension. Hyperuricaemia is a modifiable and treatable risk factor, which might reduce the incidence of Essential Hypertension (EHT). AIM: Hence, the present study was designed to find out the association between hyperuricaemia and EHT in the population of Southern Rajasthan as there is a dearth of literature on Indian scenario especially in Rajasthan. MATERIALS AND METHODS: A cross-sectional, case control study was carried out in the Department of Physiology among 125 subjects; aged 20-50 years of both sexes, which were chosen randomly from Medicine OPD and healthy volunteers. The subjects were broadly divided into two groups (A & B); group A comprised of newly diagnosed cases of EHT (n=75) and group B had healthy normotensive controls (n=50). S. Uric Acid (SUA), Serum creatinine and fasting blood glucose levels were estimated by using the respective kit methods on semi auto-analyser in both groups. S. creatinine and fasting blood glucose levels were estimated to exclude renal disorder and diabetes mellitus respectively. The data was analysed by student t-test, chi-square test and Odds Ratio. RESULTS: The mean SUA level in group A was significantly higher than group B (6.56 ± 0.76, 4.91 ± 0.97 mg/dl, p<0.001 respectively). 37.33% of patients had hyperuricaemia in group A as compared to 14% in group B (p<0.01, OR=3.66) indicating that a hyperuricaemic individual has 3.66 times more risk of developing EHT as compared to the one with lower value of SUA. CONCLUSION: The mean SUA level and the frequency of hyperuricaemia was significantly higher in newly diagnosed cases of EHT as compared to healthy controls. Hence, SUA could be useful as a potential indicator for early risk detection of development of EHT.

Superoxide anion radicals induce IGF-1 resistance through concomitant activation of PTP1B and PTEN.

The evolutionarily conserved IGF-1 signalling pathway is associated with longevity, metabolism, tissue homeostasis, and cancer progression. Its regulation relies on the delicate balance between activating kinases and suppressing phosphatases and is still not very well understood. We report here that IGF-1 signalling in vitro and in a murine ageing model in vivo is suppressed in response to accumulation of superoxide anions (O2∙-) in mitochondria, either by chemical inhibition of complex I or by genetic silencing of O2∙--dismutating mitochondrial Sod2. The O2∙--dependent suppression of IGF-1 signalling resulted in decreased proliferation of murine dermal fibroblasts, affected translation initiation factors and suppressed the expression of α1(I), α1(III), and α2(I) collagen, the hallmarks of skin ageing. Enhanced O2∙- led to activation of the phosphatases PTP1B and PTEN, which via dephosphorylation of the IGF-1 receptor and phosphatidylinositol 3,4,5-triphosphate dampened IGF-1 signalling. Genetic and pharmacologic inhibition of PTP1B and PTEN abrogated O2∙--induced IGF-1 resistance and rescued the ageing skin phenotype. We thus identify previously unreported signature events with O2∙-, PTP1B, and PTEN as promising targets for drug development to prevent IGF-1 resistance-related pathologies.

Extraribosomal l13a is a specific innate immune factor for antiviral defense.

UNLABELLED: We report a novel extraribosomal innate immune function of mammalian ribosomal protein L13a, whereby it acts as an antiviral agent. We found that L13a is released from the 60S ribosomal subunit in response to infection by respiratory syncytial virus (RSV), an RNA virus of the Pneumovirus genus and a serious lung pathogen. Unexpectedly, the growth of RSV was highly enhanced in L13a-knocked-down cells of various lineages as well as in L13a knockout macrophages from mice. In all L13a-deficient cells tested, translation of RSV matrix (M) protein was specifically stimulated, as judged by a greater abundance of M protein and greater association of the M mRNA with polyribosomes, while general translation was unaffected. In silico RNA folding analysis and translational reporter assays revealed a putative hairpin in the 3'untranslated region (UTR) of M mRNA with significant structural similarity to the cellular GAIT (gamma-activated inhibitor of translation) RNA hairpin, previously shown to be responsible for assembling a large, L13a-containing ribonucleoprotein complex that promoted translational silencing in gamma interferon (IFN-γ)-activated myeloid cells. However, RNA-protein interaction studies revealed that this complex, which we named VAIT (respiratory syncytial virus-activated inhibitor of translation) is functionally different from the GAIT complex. VAIT is the first report of an extraribosomal L13a-mediated, IFN-γ-independent innate antiviral complex triggered in response to virus infection. We provide a model in which the VAIT complex strongly hinders RSV replication by inhibiting the translation of the rate-limiting viral M protein, which is a new paradigm in antiviral defense. IMPORTANCE: The innate immune mechanisms of host cells are diverse in nature and act as a broad-spectrum cellular defense against viruses. Here, we report a novel innate immune mechanism functioning against respiratory syncytial virus (RSV), in which the cellular ribosomal protein L13a is released from the large ribosomal subunit soon after infection and inhibits the translation of a specific viral mRNA, namely, that of the matrix protein M. Regarding its mechanism, we show that the recognition of a specific secondary structure in the 3' untranslated region of the M mRNA leads to translational arrest of the mRNA. We also show that the level of M protein in the infected cell is rate limiting for viral morphogenesis, providing a rationale for L13a to target the M mRNA for suppression of RSV growth. Translational silencing of a viral mRNA by a deployed ribosomal protein is a new paradigm in innate immunity.

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

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.