Louis Chicoine - Academia.edu (original) (raw)
Papers by Louis Chicoine
The FASEB Journal, Apr 1, 2013
The FASEB Journal, Apr 1, 2013
To test the hypothesis that arginase II is induced in an oxygen‐dependent manner in human pulmona... more To test the hypothesis that arginase II is induced in an oxygen‐dependent manner in human pulmonary microvascular endothelial cells (hPMVEC), cells were incubated in either normoxia (20% O2) or hypoxia (1% O2) for 6 or 24 h, and some of the hypoxic hPMVEC were returned to normoxia or hypoxia for an additional 24 h. The hPMVEC incubated in hypoxia for 24 h produced ~70% less NO than cells incubated in normoxia (p<0.01). Greater HIF‐2α, EGFR, and arginase II protein levels were found in hypoxic hPMVEC than in normoxic cells (p<0.05). Hypoxic hPMVEC returned to normoxia had substantially greater NO production, while arginase II, HIF‐2α, and EGFR protein levels were lower, than in hypoxic hPMVEC (p<0.05). hPMVECs were transfected with siRNA for 48 h to knockdown the expression of HIF‐2α or EGFR. We found that silencing HIF‐2α prevented hypoxia‐induced EGFR and arginase II expression. Conversely, silencing of EGFR also prevented HIF‐2α and arginase II expression, as well as downstream ERK and Akt activation. These results suggest that there is a feedback regulation loop between HIF‐2α and EGFR. Pharmacological inhibition of Akt and MEK1/2 prevented hypoxia‐induced arginase II expression. Thus, arginase II is induced by hypoxia through a pathway mediated by HIF2α, EGFR, ERK, and Akt. We speculate that arginase II regulation may represent a potential therapy for pulmonary hypertension associated with hypoxia.
Archives of neurology, Sep 1, 2007
American Journal of Respiratory Cell and Molecular Biology, Mar 1, 2002
Pulmonary inflammation increases nitric oxide (NO) production via inducible nitric oxide synthase... more Pulmonary inflammation increases nitric oxide (NO) production via inducible nitric oxide synthase (iNOS). This study was performed to determine some of the factors that affect the availability of the NOS substrate, l-arginine (l-arg), in the intact lung subjected to silica-induced inflammation. Nitrate production, as an index of NO production, was significantly greater in silica-exposed lungs (53.5 ± 12.1
Neuromuscular Disorders, Oct 1, 2018
Journal of Investigative Medicine, 2001
The FASEB Journal, Apr 1, 2012
The FASEB Journal, Apr 1, 2011
Journal of Biological Chemistry, 1986
Zeitschrift Fur Geburtshilfe Und Neonatologie, Jul 14, 2005
The FASEB Journal, Apr 1, 2015
OBJECTIVES: Bronchopulmonary dysplasia (BPD) and the associated complication of pulmonary hyperte... more OBJECTIVES: Bronchopulmonary dysplasia (BPD) and the associated complication of pulmonary hypertension (PH) leads to increased mortality and a longer length of stay among survivors. Placental histopathology may give early clues of subsequent events. The objective was to evaluate the relationship of maternal vascular underperfusion (MVU) changes on placental histopathology with subsequent development of BPD-associated PH in a cohort of extremely premature infants. STUDY DESIGN: In a cohort of preterm infants ' ⩽ 28 weeks' gestational age (GA) and with 'severe' BPD, this retrospective study evaluated specific placental histopathological changes and assessed the relationship with subsequent development of PH. 'Severe' BPD was defined as the need for ⩾ 30% oxygen and/or positive pressure ventilation at 36 weeks postmenstrual age. Placental and echocardiographic assessments were done by investigators masked to the grouping and clinical outcomes. RESULTS: Fifty six infants with severe BPD formed the cohort; PH was noted in 22 (39.3%) infants. The GA of the infants with and without PH was comparable (25.8 ± 1.6 vs 25.8 ± 1.3 weeks, P = 0.9). On placental histopathological examination, 13 (23%) had features of MVU. On univariate logistic regression, the presence of changes consistent with MVU increased the relative risk of subsequent BPD-associated PH by 2.75 (95% confidence interval 1.56 to 4.85, P = 0.004). The significance persisted after adjustment for GA. Stratification by the presence or absence of fetal growth restriction, yielded nonsignificant associations (P = 0.17). CONCLUSION: Based on the results of the present study, specific placental histopathological changes may give early clues to the subsequent development of BPD-associated PH.
The FASEB Journal, Apr 1, 2009
The FASEB Journal, Mar 1, 2006
The FASEB Journal, Apr 1, 2011
American Journal of Physiology-heart and Circulatory Physiology, Jan 15, 2013
Chronic hypoxia (CH)-induced pulmonary hypertension is characterized by vasoconstriction and vasc... more Chronic hypoxia (CH)-induced pulmonary hypertension is characterized by vasoconstriction and vascular remodeling, leading to right ventricular dysfunction. Given the role of arterial compliance (Ca) in right ventricular work, a decrease in Ca would add to right ventricular work. Nitric oxide (NO) is a potent vasodilator made by NO synthases from L-arginine (L-Arg). However, little is known of the effect of L-Arg on vascular compliance (Cv) in the lung. We hypothesized that exposure to CH would decrease Ca and that this effect would be reversed by exogenous L-Arg. Sprague-Dawley rats were exposed to either normoxia or CH for 14 days; the lungs were then isolated and perfused. Vascular occlusions were performed and modeled using a three-compliance, two-resistor model. Pressure-flow curves were generated, and a distensible vessel model was used to estimate distensibility and a vascular resistance parameter (R0). Hypoxia resulted in the expected increase in arterial resistance (Ra) as well as a decrease in both Ca and Cv. L-Arg had little effect on Ra, Ca, or Cv in isolated lungs from normoxic animals. L-Arg decreased Ra in lungs from CH rats and redistributed compliance to approximately that found in normoxic lungs. CH increased R0, and L-Arg reversed this increase in R0. L-Arg increased exhaled NO, and inhibition of L-Arg uptake attenuated the L-Arg-induced increase in exhaled NO. These data demonstrate that the CH-induced decrease in Ca was reversed by L-Arg, suggesting that L-Arg may improve CH-induced right ventricular dysfunction.
Journal of Perinatology, 2016
OBJECTIVE: To predict mortality or length of stay (LOS) 4109 days (90th percentile) among infants... more OBJECTIVE: To predict mortality or length of stay (LOS) 4109 days (90th percentile) among infants with congenital diaphragmatic hernia (CDH). STUDY DESIGN: We conducted a retrospective analysis using the Children's Hospital Neonatal Database during 2010 to 2014. Infants born 434 weeks gestation with CDH admitted at 22 participating regional neonatal intensive care units were included; patients who were repaired or were at home before admission were excluded. The primary outcome was death before discharge or LOS 4109 days. Factors associated with this outcome were used to develop a multivariable equation using 80% of the cohort. Validation was performed in the remaining 20% of infants. RESULTS: The median gestation and age at referral in this cohort (n = 677) were 38 weeks and 6 h, respectively. The primary outcome occurred in 242 (35.7%) infants, and was distributed between mortality (n = 180, 27%) and LOS 4109 days (n = 66, 10%). Regression analyses showed that small for gestational age (odds ratio (OR) 2.5, P = 0.008), presence of major birth anomalies (OR 5.9, Po 0.0001), 5-min Apgar score ⩽ 3 (OR 7.0, P = 0.0002), gradient of acidosis at the time of referral (P o0.001), the receipt of extracorporeal support (OR 8.4, P o 0.0001) and bloodstream infections (OR 2.2, P = 0.004) were independently associated with death or LOS 4109 days. This model performed well in the validation cohort (area under curve (AUC) = 0.856, goodness-of-fit (GF) χ 2 , P = 0.16) and acted similarly even after omitting extracorporeal support (AUC = 0.82, GF χ 2 , P = 0.05). CONCLUSIONS: Six variables predicted death or LOS ⩾ 109 days in this large, contemporary cohort with CDH. These results can assist in risk adjustment for comparative benchmarking and for counseling affected families.
Journal of Investigative Medicine, 2004
<b>Copyright information:</b>Taken from "A translational approach for limb vascu... more <b>Copyright information:</b>Taken from "A translational approach for limb vascular delivery of the micro-dystrophin gene without high volume or high pressure for treatment of Duchenne muscular dystrophy"http://www.translational-medicine.com/content/5/1/45Journal of Translational Medicine 2007;5():45-45.Published online 24 Sep 2007PMCID:PMC2082019. A truncated MCK promoter/enhancer (563 bp) is used to drive muscle specific gene expression. Also labeled is a chimeric SV40 intron (97 bp) and synthetic polyadenylation site (53 bp). The 3,590 bp murine micro-dystrophin construction is depicted in detail. ABD is the complete actin binding domain, hinges 1, 2 and 4 are shown (green boxes), as are the flanking spectrin rod domains (SR blue boxes). The cysteine-rich dystroglycan binding domain is denoted by an orange box. AAV2 ITR are shown as arrowheads. (B) Immunofluorescence detection of micro-dystrophin expression in mouse TA muscle. rAAV1, 6, or 8.micro-dystrophin (10vg) was delivered by intramuscular injection (IM Control) or ILP through the femoral artery of 3–4 week old mice. Representative TA muscle sections (12 um) are shown from 4 week post-injected animals (8 and 12 weeks looked similar). Sections were immuno-stained with the N-terminal dystrophin antibody Manex1a. Scale Bar, 50 μm.
The FASEB Journal, Apr 1, 2013
The FASEB Journal, Apr 1, 2013
To test the hypothesis that arginase II is induced in an oxygen‐dependent manner in human pulmona... more To test the hypothesis that arginase II is induced in an oxygen‐dependent manner in human pulmonary microvascular endothelial cells (hPMVEC), cells were incubated in either normoxia (20% O2) or hypoxia (1% O2) for 6 or 24 h, and some of the hypoxic hPMVEC were returned to normoxia or hypoxia for an additional 24 h. The hPMVEC incubated in hypoxia for 24 h produced ~70% less NO than cells incubated in normoxia (p<0.01). Greater HIF‐2α, EGFR, and arginase II protein levels were found in hypoxic hPMVEC than in normoxic cells (p<0.05). Hypoxic hPMVEC returned to normoxia had substantially greater NO production, while arginase II, HIF‐2α, and EGFR protein levels were lower, than in hypoxic hPMVEC (p<0.05). hPMVECs were transfected with siRNA for 48 h to knockdown the expression of HIF‐2α or EGFR. We found that silencing HIF‐2α prevented hypoxia‐induced EGFR and arginase II expression. Conversely, silencing of EGFR also prevented HIF‐2α and arginase II expression, as well as downstream ERK and Akt activation. These results suggest that there is a feedback regulation loop between HIF‐2α and EGFR. Pharmacological inhibition of Akt and MEK1/2 prevented hypoxia‐induced arginase II expression. Thus, arginase II is induced by hypoxia through a pathway mediated by HIF2α, EGFR, ERK, and Akt. We speculate that arginase II regulation may represent a potential therapy for pulmonary hypertension associated with hypoxia.
Archives of neurology, Sep 1, 2007
American Journal of Respiratory Cell and Molecular Biology, Mar 1, 2002
Pulmonary inflammation increases nitric oxide (NO) production via inducible nitric oxide synthase... more Pulmonary inflammation increases nitric oxide (NO) production via inducible nitric oxide synthase (iNOS). This study was performed to determine some of the factors that affect the availability of the NOS substrate, l-arginine (l-arg), in the intact lung subjected to silica-induced inflammation. Nitrate production, as an index of NO production, was significantly greater in silica-exposed lungs (53.5 ± 12.1
Neuromuscular Disorders, Oct 1, 2018
Journal of Investigative Medicine, 2001
The FASEB Journal, Apr 1, 2012
The FASEB Journal, Apr 1, 2011
Journal of Biological Chemistry, 1986
Zeitschrift Fur Geburtshilfe Und Neonatologie, Jul 14, 2005
The FASEB Journal, Apr 1, 2015
OBJECTIVES: Bronchopulmonary dysplasia (BPD) and the associated complication of pulmonary hyperte... more OBJECTIVES: Bronchopulmonary dysplasia (BPD) and the associated complication of pulmonary hypertension (PH) leads to increased mortality and a longer length of stay among survivors. Placental histopathology may give early clues of subsequent events. The objective was to evaluate the relationship of maternal vascular underperfusion (MVU) changes on placental histopathology with subsequent development of BPD-associated PH in a cohort of extremely premature infants. STUDY DESIGN: In a cohort of preterm infants ' ⩽ 28 weeks' gestational age (GA) and with 'severe' BPD, this retrospective study evaluated specific placental histopathological changes and assessed the relationship with subsequent development of PH. 'Severe' BPD was defined as the need for ⩾ 30% oxygen and/or positive pressure ventilation at 36 weeks postmenstrual age. Placental and echocardiographic assessments were done by investigators masked to the grouping and clinical outcomes. RESULTS: Fifty six infants with severe BPD formed the cohort; PH was noted in 22 (39.3%) infants. The GA of the infants with and without PH was comparable (25.8 ± 1.6 vs 25.8 ± 1.3 weeks, P = 0.9). On placental histopathological examination, 13 (23%) had features of MVU. On univariate logistic regression, the presence of changes consistent with MVU increased the relative risk of subsequent BPD-associated PH by 2.75 (95% confidence interval 1.56 to 4.85, P = 0.004). The significance persisted after adjustment for GA. Stratification by the presence or absence of fetal growth restriction, yielded nonsignificant associations (P = 0.17). CONCLUSION: Based on the results of the present study, specific placental histopathological changes may give early clues to the subsequent development of BPD-associated PH.
The FASEB Journal, Apr 1, 2009
The FASEB Journal, Mar 1, 2006
The FASEB Journal, Apr 1, 2011
American Journal of Physiology-heart and Circulatory Physiology, Jan 15, 2013
Chronic hypoxia (CH)-induced pulmonary hypertension is characterized by vasoconstriction and vasc... more Chronic hypoxia (CH)-induced pulmonary hypertension is characterized by vasoconstriction and vascular remodeling, leading to right ventricular dysfunction. Given the role of arterial compliance (Ca) in right ventricular work, a decrease in Ca would add to right ventricular work. Nitric oxide (NO) is a potent vasodilator made by NO synthases from L-arginine (L-Arg). However, little is known of the effect of L-Arg on vascular compliance (Cv) in the lung. We hypothesized that exposure to CH would decrease Ca and that this effect would be reversed by exogenous L-Arg. Sprague-Dawley rats were exposed to either normoxia or CH for 14 days; the lungs were then isolated and perfused. Vascular occlusions were performed and modeled using a three-compliance, two-resistor model. Pressure-flow curves were generated, and a distensible vessel model was used to estimate distensibility and a vascular resistance parameter (R0). Hypoxia resulted in the expected increase in arterial resistance (Ra) as well as a decrease in both Ca and Cv. L-Arg had little effect on Ra, Ca, or Cv in isolated lungs from normoxic animals. L-Arg decreased Ra in lungs from CH rats and redistributed compliance to approximately that found in normoxic lungs. CH increased R0, and L-Arg reversed this increase in R0. L-Arg increased exhaled NO, and inhibition of L-Arg uptake attenuated the L-Arg-induced increase in exhaled NO. These data demonstrate that the CH-induced decrease in Ca was reversed by L-Arg, suggesting that L-Arg may improve CH-induced right ventricular dysfunction.
Journal of Perinatology, 2016
OBJECTIVE: To predict mortality or length of stay (LOS) 4109 days (90th percentile) among infants... more OBJECTIVE: To predict mortality or length of stay (LOS) 4109 days (90th percentile) among infants with congenital diaphragmatic hernia (CDH). STUDY DESIGN: We conducted a retrospective analysis using the Children's Hospital Neonatal Database during 2010 to 2014. Infants born 434 weeks gestation with CDH admitted at 22 participating regional neonatal intensive care units were included; patients who were repaired or were at home before admission were excluded. The primary outcome was death before discharge or LOS 4109 days. Factors associated with this outcome were used to develop a multivariable equation using 80% of the cohort. Validation was performed in the remaining 20% of infants. RESULTS: The median gestation and age at referral in this cohort (n = 677) were 38 weeks and 6 h, respectively. The primary outcome occurred in 242 (35.7%) infants, and was distributed between mortality (n = 180, 27%) and LOS 4109 days (n = 66, 10%). Regression analyses showed that small for gestational age (odds ratio (OR) 2.5, P = 0.008), presence of major birth anomalies (OR 5.9, Po 0.0001), 5-min Apgar score ⩽ 3 (OR 7.0, P = 0.0002), gradient of acidosis at the time of referral (P o0.001), the receipt of extracorporeal support (OR 8.4, P o 0.0001) and bloodstream infections (OR 2.2, P = 0.004) were independently associated with death or LOS 4109 days. This model performed well in the validation cohort (area under curve (AUC) = 0.856, goodness-of-fit (GF) χ 2 , P = 0.16) and acted similarly even after omitting extracorporeal support (AUC = 0.82, GF χ 2 , P = 0.05). CONCLUSIONS: Six variables predicted death or LOS ⩾ 109 days in this large, contemporary cohort with CDH. These results can assist in risk adjustment for comparative benchmarking and for counseling affected families.
Journal of Investigative Medicine, 2004
<b>Copyright information:</b>Taken from "A translational approach for limb vascu... more <b>Copyright information:</b>Taken from "A translational approach for limb vascular delivery of the micro-dystrophin gene without high volume or high pressure for treatment of Duchenne muscular dystrophy"http://www.translational-medicine.com/content/5/1/45Journal of Translational Medicine 2007;5():45-45.Published online 24 Sep 2007PMCID:PMC2082019. A truncated MCK promoter/enhancer (563 bp) is used to drive muscle specific gene expression. Also labeled is a chimeric SV40 intron (97 bp) and synthetic polyadenylation site (53 bp). The 3,590 bp murine micro-dystrophin construction is depicted in detail. ABD is the complete actin binding domain, hinges 1, 2 and 4 are shown (green boxes), as are the flanking spectrin rod domains (SR blue boxes). The cysteine-rich dystroglycan binding domain is denoted by an orange box. AAV2 ITR are shown as arrowheads. (B) Immunofluorescence detection of micro-dystrophin expression in mouse TA muscle. rAAV1, 6, or 8.micro-dystrophin (10vg) was delivered by intramuscular injection (IM Control) or ILP through the femoral artery of 3–4 week old mice. Representative TA muscle sections (12 um) are shown from 4 week post-injected animals (8 and 12 weeks looked similar). Sections were immuno-stained with the N-terminal dystrophin antibody Manex1a. Scale Bar, 50 μm.