Lipid peroxidation can be described generally as a process under which oxidants such as free radicals attack lipids containing carbon-carbon double bond(s), especially polyunsaturated fatty acids (PUFAs). Over the last four decades, an extensive body of literature regarding lipid peroxidation has shown its important role in cell biology and human health. Since the early 1970s, the total published research articles on the topic of lipid peroxidation was 98 (1970–1974) and has been increasing at almost 135-fold, by up to 13165 in last 4 years (2010–2013). New discoveries about the involvement in cellular physiology and pathology, as well as the control of lipid peroxidation, continue to emerge every day. Given the enormity of this field, this review focuses on biochemical concepts of lipid peroxidation, production, metabolism, and signaling mechanisms of two main omega-6 fatty acids lipid peroxidation products: malondialdehyde (MDA) and, in particular, 4-hydroxy-2-nonenal (4-HNE), summarizing not only its physiological and protective function as signaling molecule stimulating gene expression and cell survival, but also its cytotoxic role inhibiting gene expression and promoting cell death. Finally, overviews of in vivo mammalian model systems used to study the lipid peroxidation process, and common pathological processes linked to MDA and 4-HNE are shown.

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Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal.

Reactive oxygen species (ROS) are key signaling molecules that play an important role in the progression of inflammatory disorders. An enhanced ROS generation by polymorphonuclear neutrophils (PMNs) at the site of inflammation causes endothelial dysfunction and tissue injury. The vascular endothelium plays an important role in passage of macromolecules and inflammatory cells from the blood to tissue. Under the inflammatory conditions, oxidative stress produced by PMNs leads to the opening of inter-endothelial junctions and promotes the migration of inflammatory cells across the endothelial barrier. The migrated inflammatory cells not only help in the clearance of pathogens and foreign particles but also lead to tissue injury. The current review compiles the past and current research in the area of inflammation with particular emphasis on oxidative stress-mediated signaling mechanisms that are involved in inflammation and tissue injury.

Reactive Oxygen Species in Inflammation and Tissue Injury

Perinatal outcomes in singletons following in vitro fertilization: a meta-analysis.

Bone Morphogenetic Proteins (BMPs) are a group of signaling molecules that belongs to the Transforming Growth Factor-β (TGF-β) superfamily of proteins. Initially discovered for their ability to induce bone formation, BMPs are now known to play crucial roles in all organ systems. BMPs are important in embryogenesis and development, and also in maintenance of adult tissue homeostasis. Mouse knockout models of various components of the BMP signaling pathway result in embryonic lethality or marked defects, highlighting the essential functions of BMPs. In this review, we first outline the basic aspects of BMP signaling and then focus on genetically manipulated mouse knockout models that have helped elucidate the role of BMPs in development. A significant portion of this review is devoted to the prominent human pathologies associated with dysregulated BMP signaling.

Bone Morphogenetic Protein (BMP) signaling in development and human diseases.

Pulmonary hypertension is associated with diverse cardiac, pulmonary, and systemic diseases in neonates, infants, and older children and contributes to significant morbidity and mortality. However, current approaches to caring for pediatric patients with pulmonary hypertension have been limited by the lack of consensus guidelines from experts in the field. In a joint effort from the American Heart Association and American Thoracic Society, a panel of experienced clinicians and clinician-scientists was assembled to review the current literature and to make recommendations on the diagnosis, evaluation, and treatment of pediatric pulmonary hypertension. This publication presents the results of extensive literature reviews, discussions, and formal scoring of recommendations for the care of children with pulmonary hypertension.

Pediatric Pulmonary Hypertension: Guidelines From the American Heart Association and American Thoracic Society

Objective. This study quantified the impact of delayed childbearing (maternal age ≥35 years) on population rate changes in low birth weight (LBW; <2500 g), preterm delivery (<37 weeks), multiple births, and small for gestational age (SGA; <10th percentile) in Alberta, Canada, between 1990 (N = 42 930) and 1996 (N = 37 710). Methods. Data were obtained from the provincial notification of a live or stillbirth. Analyses included relative risk estimates and X 2 tests for trend. Potential confounding attributable to in vitro fertilization was investigated. Results. The proportion of births to women ≥35 years of age was 8.4% in 1990 and 12.6% in 1996, a 51.2% increase. Among these women, LBW delivery increased 11%, and preterm delivery increased 14%. Delayed childbearing accounted for 78% of the change in LBW rate in the population and 36% of the change in preterm delivery rate in the population. Provincial multiple birth rates increased by 15% for twins and 14% for triplets. Delayed childbearing accounted for 15% of the twin increase and 69% of the triplet increase. When in vitro fertilization pregnancies were excluded, the change was 43% for preterm rates, 100% for LBW, 14% for twins, and 9% for triplets. Delayed childbearing did not contribute to changes in singleton SGA deliveries. Conclusions. The findings suggest that the recent increase in LBW and preterm delivery is partly related to the population phenomenon of delayed childbearing. Maternal age was not related to changes in SGA, suggesting that the age effect is through pregnancy complications that lead to preterm delivery and LBW. Prospective parents should be informed about the higher risk for neonatal morbidity associated with delayed childbearing. Health care providers should be aware of the impact of delayed childbearing on health care resources. Pediatrics 2002;109:399-403; premature infants, twins, triplets, early gestation, birth weight, low birth weight.

Delayed childbearing and its impact on population rate changes in lower birth weight, multiple birth, and preterm delivery.

The purpose of this study was to use gene expression profiling to understand how adult rat lung responds to high tidal volume (HV) ventilation in vivo. HV ventilation for 30 minutes did not cause discernable lung injury (in terms of altered mechanics or histology) but caused obvious injury when continued for 90 minutes. However, at 30-minute ventilation, HV caused significant upregulation of 10 genes and suppression of 12 genes. Among the upregulated genes were transcription factors, stress proteins, and inflammatory mediators; the downregulated genes were exemplified by metabolic regulatory genes. On the basis of cluster analysis, we studied Egr-1, c-Jun, heat shock protein 70, and interleukin (IL)-1β in further detail. Temporal studies demonstrated that Egr-1 and c-Jun were increased early and before heat shock protein 70 and IL-1β. Spatial studies using in situ hybridization and laser capture microscopy revealed that all four genes were upregulated primarily in the bronchiolar airway epithelium. Furthe...

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Early changes in lung gene expression due to high tidal volume

Xanthine oxidase (XO)-derived reactive oxygen species (ROS) formation contributes to experimental chronic hypoxic pulmonary hypertension in adults, but its role in neonatal pulmonary hypertension h...

https://www.physiology.org/doi/pdf/10.1152/ajplung.00166.2007

Contribution of xanthine oxidase-derived superoxide to chronic hypoxic pulmonary hypertension in neonatal rats

We investigated the effect of high VT ventilation on adult and newborn rats by examining pulmonary injury and cytokine messenger RNA (mRNA). On the basis of compliance, edema formation, and histology, ventilation with 25 ml·kg−1 was more injurious to adult rats than newborns. Ventilation with 40 ml kg−1 minimally affected compliance in newborns but caused death in adults. Ventilation of adults for 30 minutes at 25 ml kg−1 upregulated the mRNA expression of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), macrophage inflammatory protein-2 (MIP-2), and IL-10, whereas in newborns such ventilation only increased mRNA expression of MIP-2 and IL-10. When VT was raised to 40 ml kg−1 in newborns, IL-1β mRNA levels were additionally increased at 30 minutes, whereas ventilation for 3 hours additionally increased IL-6 and TNF-α mRNA. In newborns, the addition of 100% oxygen (O2) to 30 minutes of ventilation blunted the high VT induction of IL-1β, IL-10, and MIP-2 mRNA expressions, whereas at 3 hours, 100%...

https://www.atsjournals.org/doi/pdf/10.1164/rccm.200310-1417OC

High tidal volume ventilation causes different inflammatory responses in newborn versus adult lung.

Rationale: Fluoxetine is a selective serotonin reuptake inhibitor antidepressant widely used by pregnant women. Epidemiological data suggest that fluoxetine exposure prenatally increases the prevalence of persistent pulmonary hypertension syndrome of the newborn. The mechanism responsible for this effect is unclear and paradoxical, considering the current evidence of a pulmonary hypertension protective fluoxetine effect in adult rodents.Objectives: To evaluate the fluoxetine effect on fetal rat pulmonary vascular smooth muscle mechanical properties and cell proliferation rate.Methods: Pregnant rats were treated with fluoxetine (10 mg/kg) from Day 11 through Day 21 of gestation.Measurements and Main Results: Fetuses were delivered by cesarean section. As compared with controls, fluoxetine exposure resulted in fetal pulmonary hypertension as evidenced by an increase in the weight ratio of the right ventricle to the left ventricle plus septum (P = 0.02) and by an increase in pulmonary arterial medial thickne...

https://www.atsjournals.org/doi/pdf/10.1164/rccm.200701-163OC

Jaques Belik

Papers

Delayed childbearing and its impact on population rate changes in lower birth weight, multiple birth, and preterm delivery.

Early changes in lung gene expression due to high tidal volume

Contribution of xanthine oxidase-derived superoxide to chronic hypoxic pulmonary hypertension in neonatal rats

High tidal volume ventilation causes different inflammatory responses in newborn versus adult lung.

Prenatal exposure to fluoxetine induces fetal pulmonary hypertension in the rat.