Intrauterine Programming of Cardiovascular Diseases in Maternal Diabetes

Higa, Romina; Leonardi, María Laura; Jawerbaum, Alicia

doi:10.3389/fphys.2021.760251

Cited by 7 publications

(5 citation statements)

References 89 publications

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“…In a Danish population-based cohort study, Yu et al reported that during a 40-year follow-up, offspring of mothers with pregestational diabetes had a hazard ratio (HR) of 1.29 to develop early onset CVD [ 6 ]. Although the exact mechanism remains unknown, the earliest signs of CVD could originate already in the developing fetus, possibly mediated through epigenetic mechanisms [ 21 ]. Murray et al reported that maternal risk factors during pregnancy could induce DNA methylation in the offspring’s genome at birth, which in turn, was found to be associated with enhanced arterial stiffening after a follow-up of 8–9 years [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Higher pulse wave velocity in young adult offspring of mothers with type 1 diabetes: a case–control study

Korpijaakko

Eriksson

Wasenius

et al. 2022

Cardiovasc Diabetol

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Background Offspring of mothers with type 1 diabetes have an increased risk for acquiring early onset cardiovascular disease (CVD). Arterial stiffness, measured as pulse wave velocity (PWV), is a non-invasive biomarker for CVD risk assessment. Our aim is to determine whether PWV is increased in young adult offspring of mothers with type 1 diabetes. Methods This is a case–control study carried out in the hospital district of Helsinki and Uusimaa, Finland. 75 offspring of mothers with type 1 diabetes (cases) and 84 offspring of mothers without diabetes (controls), aged 18–23 years, were enrolled in this study. All participants attended clinical assessments, including questionnaires and laboratory tests. Carotid-femoral PWV (cfPWV), carotid-radial PWV (crPWV), and PWV ratio were measured from each participant using the Complior Analyse mechanotransducer (Alam Medical, France). Student’s t-test and chi-squared test were used to assess differences between the groups. Stata 17.0, StataCorp LP (College Station, TX, USA) statistical package was used for the analysis. Results We did not observe any differences in conventional CVD risk factors: systolic blood pressure, LDL, HbA1c, and smoking between cases and controls. We detected higher cfPWV in cases 6.5 (SD ± 1.2) m/s than in controls 6.2 (SD ± 0.7) m/s, p = 0.049, after adjustments for BMI, smoking, mean arterial pressure, height, and pulse rate was made. We did not observe any difference between cases and controls regarding crPWV or PWV ratio. Additionally, we detected no sex differences. Conclusions We report a novel finding of signs of increased arterial stiffness already in young adult offspring of mothers with type 1 diabetes compared to matched offspring of mothers without diabetes. Our finding suggests that exposure to an adverse intrauterine environment of type 1 diabetes mothers may affect the vascular health of offspring already in young adulthood. Additional research within this topic is warranted.

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Section: Discussionmentioning

confidence: 99%

Higher pulse wave velocity in young adult offspring of mothers with type 1 diabetes: a case–control study

Korpijaakko

Eriksson

Wasenius

et al. 2022

Cardiovasc Diabetol

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“…Cardiovascular disease (CVD) is prevalent in the adult population and the leading cause of morbidity and mortality globally 1,2 . Pregnancy is a highly vulnerable period, where complications can influence maternal and fetal development, also potentially affecting future health in childhood and adulthood 3 . Atherosclerosis, a progressive disease characterized by the formation of lipid plaques in the arteries and the dominant cause of CVD, may begin during intrauterine life, with early lesion formation in fetal vessels associated with hypercholesterolemia during pregnancy, 3–9 adversely impacting later life.…”

Section: Introductionmentioning

confidence: 99%

“… 1 , 2 Pregnancy is a highly vulnerable period, where complications can influence maternal and fetal development, also potentially affecting future health in childhood and adulthood. 3 Atherosclerosis, a progressive disease characterized by the formation of lipid plaques in the arteries and the dominant cause of CVD, may begin during intrauterine life, with early lesion formation in fetal vessels associated with hypercholesterolemia during pregnancy, 3 , 4 , 5 , 6 , 7 , 8 , 9 adversely impacting later life. Preeclampsia (PE) is considered a risk factor for CVD later in the life of the mother and the offspring; it often involves inadequate blood flow to the placenta, leading to hypoxia or reduced oxygen supply to the fetus.…”

Section: Introductionmentioning

confidence: 99%

Evidence for hypoxia‐induced dysregulated cholesterol homeostasis in preeclampsia: Insights into the mechanisms from human placental cells and tissues

Fuenzalida,

Yañez,

Mueller

et al. 2024

The FASEB Journal

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Preeclampsia (PE) poses a considerable risk to the long‐term cardiovascular health of both mothers and their offspring due to a hypoxic environment in the placenta leading to reduced fetal oxygen supply. Cholesterol is vital for fetal development by influencing placental function. Recent findings suggest an association between hypoxia, disturbed cholesterol homeostasis, and PE. This study investigates the influence of hypoxia on placental cholesterol homeostasis. Using primary human trophoblast cells and placentae from women with PE, various aspects of cholesterol homeostasis were examined under hypoxic and hypoxia/reoxygenation (H/R) conditions. Under hypoxia and H/R, intracellular total and non‐esterified cholesterol levels were significantly increased. This coincided with an upregulation of HMG‐CoA‐reductase and HMG‐CoA‐synthase (key genes regulating cholesterol biosynthesis), and a decrease in acetyl‐CoA‐acetyltransferase‐1 (ACAT1), which mediates cholesterol esterification. Hypoxia and H/R also increased the intracellular levels of reactive oxygen species and elevated the expression of hypoxia‐inducible factor (HIF)‐2α and sterol‐regulatory‐element‐binding‐protein (SREBP) transcription factors. Additionally, exposure of trophoblasts to hypoxia and H/R resulted in enhanced cholesterol efflux to maternal and fetal serum. This was accompanied by an increased expression of proteins involved in cholesterol transport such as the scavenger receptor class B type I (SR‐BI) and the ATP‐binding cassette transporter G1 (ABCG1). Despite these metabolic alterations, mitogen‐activated‐protein‐kinase (MAPK) signaling, a key regulator of cholesterol homeostasis, was largely unaffected. Our findings indicate dysregulation of cholesterol homeostasis at multiple metabolic points in both the trophoblast hypoxia model and placentae from women with PE. The increased cholesterol efflux and intracellular accumulation of non‐esterified cholesterol may have critical implications for both the mother and the fetus during pregnancy, potentially contributing to an elevated cardiovascular risk later in life.

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“…Adverse developmental programming is directly related to cardiovascular disease in later life. The epigenetic modifications that occur in response to intra-uterine alterations have lasting effects and are known to alter cardiovascular structure and function in response to several environmental factors and maternal behaviors [1][2][3][4][5] . One of the most detrimental maternal behaviors during the perinatal period, which can deleteriously predispose offspring to cardiovascular diseases, is nicotine exposure, typically in the form of tobacco product use 6 .…”

Section: Introductionmentioning

confidence: 99%

Epigenetic upregulation of carotid body angiotensin signaling increases blood pressure

Zhu,

Wang,

Davis

et al. 2024

Preprint

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Epigenetic changes can be shaped by a wide array of environmental cues as well as maternal health and behaviors. One of the most detrimental behaviors to the developing fetus is nicotine exposure. Perinatal nicotine exposure remains a significant risk factor for cardiovascular health and in particular, hypertension. Increased basal carotid body activity and excitation are significant contributors to hypertension. This study investigated the epigenetic changes to carotid body activity induced by perinatal nicotine exposure resulting in carotid body-mediated hypertension. Using a rodent model of perinatal nicotine exposure, we show that angiotensin II type 1 receptor signaling is upregulated in the carotid bodies of nicotine-exposed offspring. These changes were attributed to an upregulation of genetic promotion as DNA methylation of AT1r and PKC occurred within intron regions, exemplifying an upregulation of genetic transcription for these genes. Nicotine increased angiotensin signaling in vitro. Carotid body reactivity to angiotensin was increased in perinatal nicotine-exposed offspring compared to control offspring. Further, carotid body denervation reduced arterial pressure as a result of suppressed efferent sympathetic activity in perinatal nicotine-exposed offspring. Our data demonstrate that perinatal nicotine exposure adversely affects carotid body afferent sensing, which augments efferent sympathetic activity to increase vasoconstrictor signaling and induce hypertension. Targeting angiotensin signaling in the carotid bodies may provide a way to alleviate hypertension acquired by adverse maternal uterine environments in general and perinatal nicotine exposure in particular.

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Intrauterine Programming of Cardiovascular Diseases in Maternal Diabetes

Cited by 7 publications

References 89 publications

Higher pulse wave velocity in young adult offspring of mothers with type 1 diabetes: a case–control study

Higher pulse wave velocity in young adult offspring of mothers with type 1 diabetes: a case–control study

Evidence for hypoxia‐induced dysregulated cholesterol homeostasis in preeclampsia: Insights into the mechanisms from human placental cells and tissues

Epigenetic upregulation of carotid body angiotensin signaling increases blood pressure

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