Analytical performance of Abbott C-16000 analyser haemolysis index and its potential use in measuring plasma cell-free haemoglobin.

Purpose: Measurement of the haemolysis index (HI) is usually performed in clinical chemistry laboratories in order to inform about whether biological analyses are influenced by in vivo or in vitro haemolysis of the specimen. Our aim was to evaluate the analytical performance of Abbott C-16000 analyser HI measurement in order to determine whether this could be used to reliably measure cell-free haemoglobin (fHB) in plasma samples. Methods: The repeatability, reproducibility, lower limit of detection (LLOD) and lower limit of quantification (LLOQ) of C-16000 HI measurement were determined as well as the potential interference of bilirubin, triglycerides and myoglobin. C-16000 HI values of biological samples with various ranges of fHB were compared to those measured using the established reference method, second-derivate spectroscopy. Results: Results: C-16000 HI determination showed excellent linear correlation with the reference method (y = 1.0043x ­ 1.248, R² = 0.998), a broad analytical measurement range (400-20,000 mg/L; y = 0.9904x + 72.972, R² = 0.999), clinically relevant LLOD (56 mg/L) and LLOQ (84 mg/L), good repeatability (coefficient of variation (CV) = 1-15%) and good reproducibility (CV = 5-7%). No interference was observed with myoglobin at concentrations as high as 35,447 mg/L, unconjugated and conjugated bilirubin (at concentrations up to 500 mg/L and 375 mg/L, respectively) or triglycerides up to 6.8 mmol/L. However, a significant underestimation of fHB concentrations was observed at higher triglyceride levels. Conclusion: This study demonstrates that Abbott C-16000 analyser HI is reliable and accurately measures plasma fHB concentrations under pathophysiological conditions except when there are high blood concentrations of triglycerides.

Systemic corticosteroids for the treatment of acute episodes of rhabdomyolysis in lipin-1-deficient patients.

Mutations in the LPIN1 gene constitute a major cause of severe rhabdomyolysis (RM). The TLR9 activation prompted us to treat patients with corticosteroids in acute conditions. In patients with LPIN1 mutations, RM and at-risk situations that can trigger RM have been treated in a uniform manner. Since 2015, these patients have also received intravenous corticosteroids. We retrospectively compared data on hospital stays by corticosteroid-treated patients vs. patients not treated with corticosteroids. Nineteen patients were hospitalized. The median number of admissions per patient was 21 overall and did not differ when comparing the 10 corticosteroid-treated patients with the 9 patients not treated with corticosteroids. Four patients in the non-corticosteroid group died during a RM (mean age at death: 5.6 years). There were no deaths in the corticosteroid group. The two groups did not differ significantly in the number of RM episodes. However, for the six patients who had RM and occasionally been treated with corticosteroids, the median number of RM episodes was significantly lower when intravenous steroids had been administered. The peak plasma creatine kinase level and the area under the curve were or tended to be higher in patients treated with corticosteroids-even after the exclusion of deceased patients or focusing on the period after 2015. The median length of stay (10 days overall) was significantly longer for corticosteroid-treated patients but was similar after the exclusion of deceased patients. The absence of deaths and the higher severity of RM observed among corticosteroid-treated patients could suggest that corticotherapy is associated with greater survival.

Splenic clearance of rigid erythrocytes as an inherited mechanism for splenomegaly and natural resistance to malaria.

BACKGROUND: In malaria-endemic areas, subjects from specific groups like Fulani have a peculiar protection against malaria, with high levels of IgM but also frequent anaemia and splenomegaly. The mechanisms underlying this phenotype remain elusive. METHODS: In a cohort study set up in Benin, West Africa, after a careful evaluation of malaria-related phenotypes, we measured the deformability of circulating erythrocytes in genetically distinct groups (including Fulani) living in sympatry, using ektacytometry and microsphiltration, a mimic of how the spleen clears rigid erythrocytes. Heritability of erythrocytes deformability was calculated, followed by a genome-wide association study (GWAS) of the same phenotype. FINDINGS: Compared to non-Fulani, Fulani displayed a higher deformability of circulating erythrocytes, pointing to an enhanced clearance of rigid erythrocytes by the spleen. This phenotype was observed in individuals displaying markers of Plasmodium falciparum infection. The heritability of this new trait was high, with a strong multigenic component. Five of the top 10 genes selected by a population structure-adjusted GWAS, expressed in the spleen, are potentially involved in splenic clearance of erythrocytes (CHERP, MB, PALLD, SPARC, PDE10A), through control of vascular tone, collagen synthesis and macrophage activity. INTERPRETATION: In specific ethnic groups, genetically-controlled processes likely enhance the innate retention of infected and uninfected erythrocytes in the spleen, explaining splenomegaly, anaemia, cryptic intrasplenic parasite loads, hyper-IgM, and partial protection against malaria. Beyond malaria-related phenotypes, inherited splenic hyper-filtration of erythrocytes may impact the pathogenesis of other hematologic diseases. FUNDING: ANR, National Geographic Society, IMEA, IRD, and Région Ile-de-France.

Involvement of CFTR in the pathogenesis of pulmonary arterial hypertension.

INTRODUCTION: A reduction in pulmonary artery relaxation is a key event in the pathogenesis of pulmonary arterial hypertension (PAH). Cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction in airway epithelial cells plays a central role in cystic fibrosis; CFTR is also expressed in pulmonary arteries and has been shown to control endothelium-independent relaxation. AIM AND OBJECTIVES: We aimed to delineate the role of CFTR in PAH pathogenesis through observational and interventional experiments in human tissues and animal models. METHODS AND RESULTS: Reverse-transcriptase quantitative PCR, confocal imaging and electron microscopy showed that CFTR expression was reduced in pulmonary arteries from patients with idiopathic PAH (iPAH) and in rats with monocrotaline-induced pulmonary hypertension (PH). Moreover, using myography on human, pig and rat pulmonary arteries, we demonstrated that CFTR activation induces pulmonary artery relaxation. CFTR-mediated pulmonary artery relaxation was reduced in pulmonary arteries from iPAH patients and rats with monocrotaline- or chronic hypoxia-induced PH. Long-term in vivo CFTR inhibition in rats significantly increased right ventricular systolic pressure, which was related to exaggerated pulmonary vascular cell proliferation in situ and vessel neomuscularisation. Pathologic assessment of lungs from patients with severe cystic fibrosis (F508del-CFTR) revealed severe pulmonary artery remodelling with intimal fibrosis and medial hypertrophy. Lungs from homozygous F508delCftr rats exhibited pulmonary vessel neomuscularisation. The elevations in right ventricular systolic pressure and end diastolic pressure in monocrotaline-exposed rats with chronic CFTR inhibition were more prominent than those in vehicle-exposed rats. CONCLUSIONS: CFTR expression is strongly decreased in pulmonary artery smooth muscle and endothelial cells in human and animal models of PH. CFTR inhibition increases vascular cell proliferation and strongly reduces pulmonary artery relaxation.

Author Correction: Airway surface liquid acidification initiates host defense abnormalities in Cystic Fibrosis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

NSE & S100B protein blood level assessment during a long-distance trail race.

The acute and chronic consequences of long-distance running on brain function have received little attention. The impact of such a hard-physical burden associated with sleep privation during such events such has never been explored in terms of neuropsychological function and brain damage. METHODS: Blood samples were collected from 4 athletes before, during and at the end of one of two races: Grand Raid de la Réunion 2017 (GRR: 165 km, elevation gain: 9529 m, 2 runners) and Trail de la Bourbon 2017 (TB: 111 km, elevation gain: 6433 m, 2 runners). Serum S100B and NSE levels were measured for each runner before, during and after the race. RESULTS: Serum S100B levels (normal range: < 0.15 µg/L) increased early during the race and remained high up to the end of the race in all 4 runners (range: 0.17-0.59 µg/L). NSE level (normal range: < 15 µg/L) increased in 3 of the 4 runners (range: 16.8-39.2 µg/L). CONCLUSIONS: This preliminary study shows the potential interest of S100B and NSE serum assessment during long-distance races. Further studies are needed to confirm these results and to investigate the origins and significance of this increase in brain injury markers.

Airway surface liquid acidification initiates host defense abnormalities in Cystic Fibrosis.

Cystic fibrosis (CF) is caused by defective Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. Morbidity is mainly due to early airway infection. We hypothesized that S. aureus clearance during the first hours of infection was impaired in CF human Airway Surface Liquid (ASL) because of a lowered pH. The ASL pH of human bronchial epithelial cell lines and primary respiratory cells from healthy controls (WT) and patients with CF was measured with a pH microelectrode. The antimicrobial capacity of airway cells was studied after S. aureus apical infection by counting surviving bacteria. ASL was significantly more acidic in CF than in WT respiratory cells. This was consistent with a defect in bicarbonate secretion involving CFTR and SLC26A4 (pendrin) and a persistent proton secretion by ATP12A. ASL demonstrated a defect in S. aureus clearance which was improved by pH normalization. Pendrin inhibition in WT airways recapitulated the CF airway defect and increased S. aureus proliferation. ATP12A inhibition by ouabain decreased bacterial proliferation. Antimicrobial peptides LL-37 and hBD1 demonstrated a pH-dependent activity. Normalizing ASL pH might improve innate airway defense in newborns with CF during onset of S. aureus infection. Pendrin activation and ATP12A inhibition could represent novel therapeutic strategies to normalize pH in CF airways.

Characterization of two rat models of cystic fibrosis-KO and F508del CFTR-Generated by Crispr-Cas9.

BACKGROUND: Genetically engineered animals are essential for gaining a proper understanding of the disease mechanisms of cystic fibrosis (CF). The rat is a relevant laboratory model for CF because of its zootechnical capacity, size, and airway characteristics, including the presence of submucosal glands. METHODS: We describe the generation of a CF rat model (F508del) homozygous for the p.Phe508del mutation in the transmembrane conductance regulator (Cftr) gene. This model was compared to new Cftr -/- rats (CFTR KO). Target organs in CF were examined by histological staining of tissue sections and tooth enamel was quantified by micro-computed tomography. The activity of CFTR was evaluated by nasal potential difference (NPD) and short-circuit current measurements. The effect of VX-809 and VX-770 was analyzed on nasal epithelial primary cell cultures from F508del rats. RESULTS: Both newborn F508del and Knock out (KO) animals developed intestinal obstruction that could be partly compensated by special diet combined with an osmotic laxative. The two rat models exhibited CF phenotypic anomalies such as vas deferens agenesis and tooth enamel defects. Histology of the intestine, pancreas, liver, and lungs was normal. Absence of CFTR function in KO rats was confirmed ex vivo by short-circuit current measurements on colon mucosae and in vivo by NPD, whereas residual CFTR activity was observed in F508del rats. Exposure of F508del CFTR nasal primary cultures to a combination of VX-809 and VX-770 improved CFTR-mediated Cl- transport. CONCLUSIONS: The F508del rats reproduce the phenotypes observed in CFTR KO animals and represent a novel resource to advance the development of CF therapeutics.

Human catalase gene promoter haplotype and cardiometabolic improvement after bariatric surgery.

Although its powerful impact on most co-morbidities has been widely demonstrated, the metabolic outcomes of bariatric surgery (BS) show a great heterogeneity among patients. Haplotypes of one of the major antioxidant enzyme, catalase (CAT), are associated with hypertension, dyslipidemia, and diabetes. The haplotype referred to as CAT1 includes homozygous carriers of CATH1 [-844G,-89A,-20T], whereas CAT2 haplotype includes heterozygous carriers (CATH1/CATH2) and CATH2 homozygous [-844A,-89T,-20C]. The aim of our study was to evaluate the impact of CAT1 and CAT2 haplotypes on traditional cardiovascular and metabolic markers one year after BS in a women population. The 294 women with a body mass index (BMI) >35 kg/m2 were followed-up for one year after BS, monitoring their anthropometric, metabolic and inflammatory parameters. CAT1 patients had significantly improved diastolic blood pressure (DBP) and Creactive protein (CRP) levels compared to CAT2 one year after BS. In untreated women at baseline, the change of CRP one year after BS was higher in CAT1 patients. In the population of women receiving at least one anti-lipidic, anti-hypertensive or anti-diabetic treatment at baseline, DBP and fat mass were lower one year after BS in CAT1 patients and the greater change of fat mass was associated with a higher change of adiponectin. The results highlight the beneficial impact of the CAT1 haplotype on traditional cardiovascular and metabolic parameters after BS. Our findings suggest that the CAT1 haplotype could be implicated in the level of metabolic and cardiovascular improvement after BS.

Reduced endothelial thioredoxin-interacting protein protects arteries from damage induced by metabolic stress in vivo.

Although thioredoxin-interacting protein (TXNIP) is involved in a variety of biologic functions, the contribution of endothelial TXNIP has not been well defined. To investigate the endothelial function of TXNIP, we generated a TXNIP knockout mouse on the Cdh5-cre background (TXNIPfl/fl cdh5cre). Control (TXNIPfl/fl) and TXNIPfl/fl cdh5cre mice were fed a high protein-low carbohydrate (HP-LC) diet for 3 mo to induce metabolic stress. We found that TXNIPfl/fl and TXNIPfl/fl cdh5cre mice on an HP-LC diet displayed impaired glucose tolerance and dyslipidemia concretizing the metabolic stress induced. We evaluated the impact of this metabolic stress on mice with reduced endothelial TXNIP expression with regard to arterial structure and function. TXNIPfl/fl cdh5cre mice on an HP-LC diet exhibited less endothelial dysfunction than littermate mice on an HP-LC diet. These mice were protected from decreased aortic medial cell content, impaired aortic distensibility, and increased plasminogen activator inhibitor 1 secretion. This protective effect came with lower oxidative stress and lower inflammation, with a reduced NLRP3 inflammasome expression, leading to a decrease in cleaved IL-1ß. We also show the major role of TXNIP in inflammation with a knockdown model, using a TXNIP-specific, small interfering RNA included in a lipoplex. These findings demonstrate a key role for endothelial TXNIP in arterial impairments induced by metabolic stress, making endothelial TXNIP a potential therapeutic target.-Bedarida, T., Domingues, A., Baron, S., Ferreira, C., Vibert, F., Cottart, C.-H., Paul, J.-L., Escriou, V., Bigey, P., Gaussem, P., Leguillier, T., Nivet-Antoine, V. Reduced endothelial thioredoxin-interacting protein protects arteries from damage induced by metabolic stress in vivo.

Distribution of trans-resveratrol and its metabolites after acute or sustained administration in mouse heart, brain, and liver.

SCOPE: Trans-resveratrol is widely studied for its potentially beneficial effects on numerous disorders. It is rapidly metabolized and its metabolites can exhibit biological activity. The present study aimed to investigate whether acute or sustained trans-resveratrol administration impacted on the distribution of trans-resveratrol and its metabolites in brain, heart, and liver. METHODS AND RESULTS: We used ultra-HPLC quadrupole-TOF (UHPLC-Q-TOF) in a full-scan mode to identify and assess large numbers of resveratrol metabolites. For acute intake, mice were overfed with a single dose of trans-resveratrol (150 mg/kg) and organs were collected after 30 and 60 min. For sustained intake, trans-resveratrol was given in the chow (0.04% w/w corresponding to 40 mg/kg/day), and plasma and the organs were collected after 3 months of this resveratrol diet. We found that trans-resveratrol-3-O-glucuronide and resveratrol-3-sulfate were the main metabolites found after acute intake, and free trans-resveratrol (in the brain and heart) and dihydroresveratrol derivatives were found after sustained administration CONCLUSIONS: Our results show notable differences between acute and sustained administration of trans-resveratrol and distribution of trans-resveratrol and its metabolites in mouse heart, brain, and liver. The results suggest a strategy for development of galenic forms of resveratrol.

Analysis of nasal potential in murine cystic fibrosis models.

The nasal epithelium of the mouse closely mimics the bioelectrical phenotype of the human airways. Ion transport across the nasal epithelium induces a nasal transepithelial potential difference. Its measurement by a relatively non-invasive method adapted from humans allows in vivo longitudinal measurements of CFTR-dependent ionic transport in the murine nasal mucosa. This test offers a useful tool to assess CFTR function in preclinical studies for novel therapeutics modulating CFTR activity. Here we extensively review work done to assess transepithelial transport in the murine respiratory epithelium in the basal state and after administration of CFTR modulators. Factors of variability and discriminative threshold between the CF and the WT mice for different readouts are discussed.

Three Novel Candidate Probiotic Strains with Prophylactic Properties in a Murine Model of Cow's Milk Allergy.

Food allergies can have significant effects on morbidity and on quality of life. Therefore, the development of efficient approaches to reduce the risk of developing food allergies is of considerable interest. The aim of this study was to identify and select probiotic strains with preventive properties against allergies using a combination of in vitro and in vivo approaches. To that end, 31 strains of bifidobacteria and lactic acid bacteria were screened for their immunomodulatory properties in two cellular models, namely, human peripheral blood mononuclear cells (PBMCs) and T helper 2 (Th2)-skewed murine splenocytes. Six strains inducing a high interleukin-10 (IL-10)/IL-12p70 ratio and a low secretion of IL-4 on the two cellular models were selected, and their protective impact was tested in vivo in a murine model of food allergy to ß-lactoglobulin. Three strains showed a protective impact on sensitization, with a decrease in allergen-specific IgE, and on allergy, with a decrease in mast cell degranulation. Analysis of the impact of these three strains on the T helper balance revealed different mechanisms of action. The Lactobacillus salivarius LA307 strain proved to block Th1 and Th2 responses, while the Bifidobacterium longum subsp. infantis LA308 strain induced a pro-Th1 profile and the Lactobacillus rhamnosus LA305 strain induced pro-Th1 and regulatory responses. These results demonstrate that a combination of in vitro and in vivo screening is effective in probiotic strain selection and allowed identification of three novel probiotic strains that are active against sensitization in mice.

Resveratrol Decreases TXNIP mRNA and Protein Nuclear Expressions With an Arterial Function Improvement in Old Mice.

Aging leads to a high prevalence of glucose intolerance and cardiovascular diseases, with oxidative stress playing a potential role. Resveratrol has shown promising effects on glucose tolerance and tends to improve endothelial function in elderly patients. Thioredoxin-interacting protein (TXNIP) was recently proposed as a potential link connecting glucose metabolism to oxidative stress. Here, we investigated the resveratrol-induced improvement of arterial aging phenotype in old mice and the expression of aortic TXNIP. Using an in vivo model of old mice with or without 3-month resveratrol treatment, we investigated the effects of resveratrol on age-related impairments from a cardiovascular Doppler analysis, to a molecular level, by studying inflammation and oxidative stress factors. We found a dual effect of resveratrol, with a decrease of age-related glucose intolerance and oxidative stress imbalance leading to reduced matrix remodeling that forestalls arterial aging phenotype in terms of intima-media thickness and arterial distensibility. These results provide the first evidence that aortic TXNIP mRNA and protein nuclear expressions are increased in the arterial aging and decreased by resveratrol treatment. In conclusion, we demonstrated that resveratrol helped to restore several aging impaired processes in old mice, with a decrease of aortic TXNIP mRNA and protein nuclear expressions.

High-protein-low-carbohydrate diet: deleterious metabolic and cardiovascular effects depend on age.

High-protein-low-carbohydrate (HP-LC) diets have become widespread. Yet their deleterious consequences, especially on glucose metabolism and arteries, have already been underlined. Our previous study (2) has already shown glucose intolerance with major arterial dysfunction in very old mice subjected to an HP-LC diet. The hypothesis of this work was that this diet had an age-dependent deleterious metabolic and cardiovascular outcome. Two groups of mice, young and adult (3 and 6 mo old), were subjected for 12 wk to a standard or to an HP-LC diet. Glucose and lipid metabolism was studied. The cardiovascular system was explored from the functional stage with Doppler-echography to the molecular stage (arterial reactivity, mRNA, immunohistochemistry). Young mice did not exhibit any significant metabolic modification, whereas adult mice presented marked glucose intolerance associated with an increase in resistin and triglyceride levels. These metabolic disturbances were responsible for cardiovascular damages only in adult mice, with decreased aortic distensibility and left ventricle dysfunction. These seemed to be the consequence of arterial dysfunctions. Mesenteric arteries were the worst affected with a major oxidative stress, whereas aorta function seemed to be maintained with an appreciable role of cyclooxygenase-2 to preserve endothelial function. This study highlights for the first time the age-dependent deleterious effects of an HP-LC diet on metabolism, with glucose intolerance and lipid disorders and vascular (especially microvessels) and cardiac functions. This work shows that HP-LC lead to equivalent cardiovascular alterations, as observed in very old age, and underlines the danger of such diet.

Resveratrol metabolism in a non-human primate, the grey mouse lemur (Microcebus murinus), using ultra-high-performance liquid chromatography-quadrupole time of flight.

The grey mouse lemur (Microcebus murinus) is a non-human primate used to study the ageing process. Resveratrol is a polyphenol that may increase lifespan by delaying age-associated pathologies. However, no information about resveratrol absorption and metabolism is available for this primate. Resveratrol and its metabolites were qualitatively and quantitatively analyzed in male mouse-lemur plasma (after 200 mg.kg-1 of oral resveratrol) by ultra-high performance liquid chromatography (UHPLC), coupled to a quadrupole-time-of-flight (Q-TOF) mass spectrometer used in full-scan mode. Data analyses showed, in MSE mode, an ion common to resveratrol and all its metabolites: m/z 227.072, and an ion common to dihydro-resveratrol metabolites: m/z 229.08. A semi-targeted study enabled us to identify six hydrophilic resveratrol metabolites (one diglucurono-conjugated, two monoglucurono-conjugated, one monosulfo-conjugated and two both sulfo- and glucurono-conjugated derivatives) and three hydrophilic metabolites of dihydro-resveratrol (one monoglucurono-conjugated, one monosulfo-conjugated, and one both sulfo- and glucurono-conjugated derivatives). The presence of such metabolites has been already detected in the mouse, rat, pig, and humans. Free resveratrol was measurable for several hours in mouse-lemur plasma, and its two main metabolites were trans-resveratrol-3-O-glucuronide and trans-resveratrol-3-sulfate. Free dihydro-resveratrol was not measurable whatever the time of plasma collection, while its hydrophilic metabolites were present at 24 h after intake. These data will help us interpret the effect of resveratrol in mouse lemurs and provide further information on the inter-species characteristics of resveratrol metabolism.

Dual effects of resveratrol on arterial damage induced by insulin resistance in aged mice.

Aging leads to increased insulin resistance and arterial dysfunction, with oxidative stress playing an important role. This study explored the metabolic and arterial effects of a chronic treatment with resveratrol, an antioxidant polyphenol compound that has been shown to restore insulin sensitivity and decrease oxidative stress, in old mice with or without a high-protein diet renutrition care. High-protein diet tended to increase insulin resistance and atheromatous risk. Resveratrol improved insulin sensitivity in old mice fed standard diet by decreasing homeostasis model of assessment-insulin resistance and resistin levels. However, resveratrol did not improve insulin resistance status in old mice receiving the high-protein diet. In contrast, resveratrol exhibited deleterious effects by increasing inflammation state and superoxide production and diminishing aortic distensibility. In conclusion, we demonstrate that resveratrol has beneficial or deleterious effects on insulin sensitivity and arterial function, depending on nutritional status in our models.

Review of recent data on the metabolism, biological effects, and toxicity of resveratrol in humans.

Several recently published clinical trials have extended our knowledge on the use of resveratrol (RVT) to treat several human pathological and metabolic disorders. Herein, we present insights into the metabolism, biological effects, and toxicity of RVT in humans. Recent data show that RVT exhibits antioxidant and anti-inflammatory activities. It can also improve glucose and lipid metabolism, it acts on cardiovascular parameters, and can modify some pathways involved in carcinogenesis. However, these effects are mostly tiny and the results are sometimes controversial as they depend on the protocols (i.e. dose, form of administration, patients' characteristics, adjuvant therapy, etc.). Toxicological data confirm that RVT is well tolerated. Any adverse effects (mainly concerning the abdomen), at doses of ≥0.5 g/day for long periods, remain moderate and reversible. Nevertheless, the efficacy and safety of RVT need to be further investigated.

Relationship between catalase haplotype and arterial aging.

BACKGROUND: Although many conventional factors have been associated with the development of arterial aging, cardiovascular diseases remain the first cause of death in old age. Therefore, identification of new risk factors may prove promising for monitoring this serious health problem. Oxidative stress and particularly catalase (CAT), an antioxidant enzyme, play an important role in endothelial cell pathophysiology, in shear stress response and ultimately in arterial aging. OBJECTIVE: Examine the relationships between CAT haplotypes and phenotypes of arterial aging (mean internal diameter, mean intima-media thickness of the common carotid arteries (CCA), presence of atheromatous plaques) in two French cohorts. METHODS AND RESULTS: 564 middle-aged French individuals (mean age 53 ± 12 years) from two cohorts (ERA and STANISLAS cohorts) were included in the study. Blood pressure, CCA intima-media thickness, CCA internal diameter and number of atheromatous plaques were measured. Catalase rs769214 SNP genotyping was performed. We identified a CAT haplotype that influences arterial aging. Individuals carrying the CAT2 haplotype had a higher mean internal diameter of CCA with aging and/or with an SBP ≥140 mmHg and were associated with a greater number of atheromatous plaques than CAT1 haplotypes carriers. This CAT2 haplotype appeared as an independent risk factor of arterial aging, similarly to previously identified factors such as age, systolic blood pressure, male, sex, tobacco use, hs-CRP, BMI and diabetes. CONCLUSION: The present study highlights the roles of CAT haplotypes in arterial aging and underlines the beneficial impact of the CAT1 haplotype on mean internal diameter of the CCA and atheromatous plaque number as well as on potential associated diseases.