Prenatal Nicotine Increases Matrix Metalloproteinase 2 (MMP-2) Expression in Fetal Guinea Pig Hearts

Thompson, Loren P.; Liu, Hongshan; Evans, LaShauna C.; Mong, Jessica A.

doi:10.1177/1933719111404605

Cited by 8 publications

(10 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, antenatal maternal treatment with a glutathione precursor (NAC) was tested, in order to prevent the long‐lasting vascular effects of FGR. Previous studies using diverse models of FGR in guinea‐pigs have demonstrated that maternal treatment with NAC reduces markers of oxidative stress in different cardiovascular tissues . The present results showed that antenatal treatment with NAC was associated with a normal perinatal and post‐natal growth, and endothelial function.…”

Section: Discussionsupporting

confidence: 70%

Adult vascular dysfunction in foetal growth‐restricted guinea‐pigs is associated with a neonate‐adult switching in Nos3 DNA methylation

et al. 2019

View full text Add to dashboard Cite

Aim Foetal growth restriction (FGR) is associated with endothelial dysfunction and cardiovascular diseases in adult subjects. Early vascular remodelling and epigenetic changes occurring on key endothelial genes might precede this altered vascular function. Further, it has been proposed that oxidative stress during development may determine some of these epigenetic modifications. To address this issue, we studied the in vivo and ex vivo vascular function and Nos3 promoter DNA methylation in arteries from eight‐month‐old guinea‐pig born from control, FGR‐treated and FGR‐NAC‐treated pregnancies. Methods Femoral and carotid arteries in vivo vascular function were determined by Doppler, whilst ex vivo vascular function and biomechanical properties were assessed by wire myography. Levels of eNOS mRNA and site‐specific DNA methylation in Nos3 promoter in aorta endothelial cells (AEC) were determined by qPCR and pyrosequencing respectively. Results FGR adult showed an increased femoral vascular resistance (P < .05), stiffness (P < .05) and arterial remodelling (P < .01), along with an impaired NO‐mediated relaxation (P < .001). These effects were prevented by maternal treatment with NAC. Endothelial‐NOS mRNA levels were decreased in FGR adult compared with control and FGR‐NAC (P < .05), associated with increased DNA methylation levels (P < .01). Comparison of Nos3 DNA methylation in AEC showed a differential methylation pattern between foetal and adult guinea‐pigs (P < .05). Conclusion Altogether, these data suggest that adult vascular dysfunction in the FGR does not result from early changes in Nos3 promoter DNA methylation, but from an altered vessel structure established during foetal development.

show abstract

Section: Discussionsupporting

confidence: 70%

Adult vascular dysfunction in foetal growth‐restricted guinea‐pigs is associated with a neonate‐adult switching in Nos3 DNA methylation

et al. 2019

View full text Add to dashboard Cite

show abstract

“…In the guinea pig fetal heart, prenatal hypoxia increases protein levels of MMP- 9 and activity of MMP-2 (Oh et al 2008) while prenatal nicotine increases protein levels of the active form of MMP-2 (Thompson et al 2011). Since MMP-9 is expressed in the developing hippocampus, we tested whether in utero exposure to hypoxia and/or nicotine increased MMP-9 protein levels in the CA1 region of the fetal hippocampus.…”

Section: Resultsmentioning

confidence: 99%

“…After sucrose embedding, the brains were frozen on dry ice and stored at −80°C until processed for immunocytochemistry. On a technical note, the animals were not transcardially perfused with fixative because the peripheral organs including the heart were harvested for a separate study (Thompson et al 2011). …”

Section: Methodsmentioning

confidence: 99%

“…Previous work using this model has shown that maternal exposure to either hypoxia (Oh et al 2008) or nicotine (Thompson et al 2011) increases the expression and/or activity of MMP-2 and MMP-9 in the fetal heart. Matrix metalloproteinases (MMPs) are zinc-binding peptidases that function to remodel the extracellular matrix through cleavage (Zitka et al 2010).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Differential Responses of Hippocampal Neurons and Astrocytes to Nicotine and Hypoxia in the Fetal Guinea Pig

et al. 2012

Self Cite

View full text Add to dashboard Cite

In utero exposure to cigarette smoke has severe consequences for the developing fetus, including increased risk of birth complications and behavioral and learning disabilities later in life. Evidence from animal models suggests that the cognitive deficits may be a consequence of in utero nicotine exposure in the brain during critical developmental periods. However, maternal smoking exposes the fetus to not only nicotine but also a hypoxic intrauterine environment. Thus, both nicotine and hypoxia are capable of initiating cellular cascades, leading to long-term changes in synaptic patterning that have the potential to affect cognitive functions. The present study investigates the combined effect of in utero exposure to nicotine and hypoxia on neuronal and glial elements in the hippocampal CA1 field. Fetal guinea pigs were exposed in utero to normoxic or hypoxic conditions in the presence or absence of nicotine. Hypoxia increased the protein levels of matrix metalloproteinase-9 (MMP-9) and synaptophysin and decreased the neural density as measured by NeuN immunoreactivity (ir). Nicotine exposure had no effect on these neuronal parameters but dramatically increased the density of astrocytes immunopositive for glial fibrillary acidic protein (GFAP). Further investigation into the effects of in utero nicotine exposure revealed that both GFAP-ir and NeuN-ir in the CA1 field were significantly reduced in adulthood. Taken together, our data suggest that prenatal exposure to nicotine and hypoxia not only alters synaptic patterning acutely during fetal development, but that nicotine also has long-term consequences that are observed well into adulthood. Moreover, these effects most likely take place through distinct mechanisms.

show abstract

“…Similarly, low birth weight adult guinea pigs have increased stiffness in conduit arteries (Thompson et al . ) along with a decreased NOS‐mediated relaxation that is not further impaired by the exposure to an obesogenic diet (Thompson et al . ).…”

Section: Introductionmentioning

confidence: 99%

Guinea pig models for translation of the developmental origins of health and disease hypothesis into the clinic

Morrison

Botting

Darby

et al. 2018

The Journal of Physiology

Self Cite

116

108

View full text Add to dashboard Cite

Over 30 years ago Professor David Barker first proposed the theory that events in early life could explain an individual's risk of non-communicable disease in later life: the developmental origins of health and disease (DOHaD) hypothesis. During the 1990s the validity of the DOHaD hypothesis was extensively tested in a number of human populations and the mechanisms underpinning it characterised in a range of experimental animal models. Over the past decade, researchers have sought to use this mechanistic understanding of DOHaD to develop therapeutic interventions during pregnancy and early life to improve adult health. A variety of animal models have been used to develop and evaluate interventions, each with strengths and limitations. It is becoming apparent that effective translational research requires that the animal paradigm selected mirrors the tempo of human fetal growth and development as closely as possible so that the effect of a perinatal insult and/or therapeutic intervention can be fully assessed. The guinea pig is one such animal model that over the past two decades has demonstrated itself to be a very useful platform for these important reproductive studies. This review highlights similarities in the in utero development between humans and guinea pigs, the strengths and limitations of the guinea pig as an experimental model of DOHaD and the guinea pig's potential to enhance clinical therapeutic innovation to improve human health.

show abstract

Prenatal Nicotine Increases Matrix Metalloproteinase 2 (MMP-2) Expression in Fetal Guinea Pig Hearts

Cited by 8 publications

References 47 publications

Adult vascular dysfunction in foetal growth‐restricted guinea‐pigs is associated with a neonate‐adult switching in Nos3 DNA methylation

Adult vascular dysfunction in foetal growth‐restricted guinea‐pigs is associated with a neonate‐adult switching in Nos3 DNA methylation

Differential Responses of Hippocampal Neurons and Astrocytes to Nicotine and Hypoxia in the Fetal Guinea Pig

Guinea pig models for translation of the developmental origins of health and disease hypothesis into the clinic

Contact Info

Product

Resources

About