The Early Origins of Cardiovascular Health and Disease: Who, When, and How

Rueda-Clausen, Christian F.; Morton, Jude S.; Davidge, Sandra T.

doi:10.1055/s-0031-1275520

Cited by 50 publications

(39 citation statements)

References 137 publications

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“…Of note, multigenerational highaltitude populations demonstrate protection against the effects of high-altitude hypoxia on fetal growth (14)(15)(16)(17)(18). Experimental studies in animal models support the likelihood that prenatal hypoxia can program cardiac, vascular, and metabolic dysfunction in the adult offspring (19)(20)(21), and that high-altitude ancestry protects against the effect of chronic hypoxic development on fetal growth (22).…”

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Graduated effects of high-altitude hypoxia and highland ancestry on birth size

et al. 2013

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Background: We present a cohort of ca. 25,000 birth records from Bolivia of men and women who are currently adults. We used this cohort to test the hypothesis that high altitude reduces birth weight and that highland ancestry confers graduated protection against this effect. Methods: Birth records were obtained from obstetric clinics and hospitals in La Paz (3,600 m) and Santa Cruz (420 m). Only singleton, healthy term (>37 wk) pregnancies of nonsmoking mothers were included. Andean, Mestizo, or European ancestry was determined by validated analysis of parental surnames. results: High altitude reduced body weight (3,396 ± 3 vs. 3,090 ± 6 g) and length (50.8 ± 0 vs. 48.7 ± 0 cm) at birth (P < 0.001). Highland ancestry partially protected against the effects of high altitude on birth weight (Andean = 3,148 ± 15 g; Mestizo = 3,081 ± 6 g; and European = 2,957 ± 32 g; trend P < 0.001) but not on birth length. The effects of high-altitude pregnancy on birth size were similar for male and female babies. conclusion: High altitude reduces birth weight and highland native ancestry confers graduated protection. Given previous studies linking reduced birth weight with increased risk of cardiovascular disease, further study is warranted to test whether adults from high-altitude pregnancy are at increased risk of developing cardiovascular disease.i n addition to the interaction between our genetic makeup and traditional lifestyle risk factors, such as smoking and obesity, it is now accepted that the quality of the environment in prenatal life programs cardiovascular health and the risk of developing heart disease (1). Overwhelming evidence derived from human studies dating back more than two decades and encompassing six continents now links development under suboptimal intrauterine conditions with low birth weight and increased rates of coronary heart disease and the metabolic syndrome (2-8). Epidemiologic studies relating the type of suboptimal intrauterine condition with physiological dysfunction in later life have largely focused on human populations undergoing alterations in maternal nutrition or on human pregnancy affected by maternal psychological stress or by exposure to stress hormones (9-11). This focus on the nutrient supply to the fetus or on maternofetal stress in humans is supported by a large number of investigations in experimental animal models demonstrating that cardiovascular dysfunction in adulthood can be programmed in pregnancy by inappropriate nutrition or by exposure to glucocorticoid excess (1,12,13).In addition to the alterations in maternal nutrition and maternal stress, fetal hypoxia is one of the most common suboptimal conditions in complicated pregnancy. More than 140 million people live at altitudes >2,500 m where lowered oxygen availability has been shown to reduce fetal growth and birth weight, thus comprising the largest single human group at risk for fetal growth restriction. Of note, multigenerational highaltitude populations demonstrate protection against the effects of high-altitude hypoxi...

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Graduated effects of high-altitude hypoxia and highland ancestry on birth size

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“…Numerous epidemiological and animal studies have shown that stressors such as hypoxia can influence the growth and developmental trajectories of the fetus, thereby increasing its susceptibility to long-term health complications, including cardiovascular diseases (reviewed in Rueda-Clausen et al 1 ). In support of this, we and others have shown that prenatal hypoxia is associated with long-term alterations in vascular function, characterized by reduced NO-mediated vasodilation, as well as increased responsiveness to adrenergic vasoconstrictors.…”

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Prenatal Hypoxia Causes Long-Term Alterations in Vascular Endothelin-1 Function in Aged Male, but Not Female, Offspring

et al. 2013

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Fetal hypoxia is believed to be an important pathogenetic factor in a number of pregnancy-related complications such as preeclampsia and intrauterine growth restriction (IUGR). Numerous epidemiological and animal studies have shown that stressors such as hypoxia can influence the growth and developmental trajectories of the fetus, thereby increasing its susceptibility to long-term health complications, including cardiovascular diseases (reviewed in Rueda-Clausen et al 1 ). In support of this, we and others have shown that prenatal hypoxia is associated with long-term alterations in vascular function, characterized by reduced NO-mediated vasodilation, as well as increased responsiveness to adrenergic vasoconstrictors. [2][3][4] ET-1 is a polypeptide that plays an integral role in vascular function. By virtue of its potent vasoconstrictor properties and its capacity to induce vascular remodeling, ET-1 signaling is believed to be important in the progression of diseases where vascular dysfunction plays a role. 5,6 The vasoactive peptide ET-1 is synthesized as an inactive precursor, big ET-1 (bET-1), which is then subsequently cleaved by 1 of several enzymes, including the endothelin (ET)-converting enzymes (ECE), certain members of the matrix-metalloproteinase (MMP) family (notably the gelatinases), chymase and neutral endopeptidase. 7 Recently, we showed that NO plays a role in regulating the conversion of bET-1 to active ET-1, 8 and consequently conditions of NO deficiency, such as IUGR, may also be associated with increased ET-1 activity. Collectively, these studies provided us the impetus to investigate whether prenatal hypoxia confers on the offspring an altered circulatory phenotype, characterized by increased ET-1 signaling, and determine whether male and female offspring were similarly affected. MethodsExpanded methods are available in the online-only Data Supplement. Briefly, the experimental protocols described herein were approved by the University of Alberta Health Sciences Animal Policy and Welfare Committee in accordance with the See Editorial Commentary, pp 685-686Abstract-Prenatal hypoxia can alter the growth trajectory of the fetus and cause lasting health complications including vascular dysfunction. We hypothesized that offspring that were intrauterine growth restricted (IUGR) because of prenatal hypoxia would exhibit altered vascular endothelin-1 (ET-1) signaling in later life. Isolated mesenteric artery responses to big ET-1 (bET-1) and ET-1 were assessed by using wire myography. Male IUGR offspring had 3-fold greater bET-1-induced vasoconstriction compared with controls (n=7 per group; P<0.001); NO synthase inhibition with L-N G -nitroarginine-methyl ester potentiated bET-1-induced vasoconstriction, albeit this effect was 2-fold greater (P<0.05) in male control compared with IUGR offspring. Vascular responses to bET-1 were similar between female IUGR and control offspring (n=9-11 per group). In the presence of L-N G -nitro-arginine-methyl ester, pretreatment with the chymase inhibitor chymosta...

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“…Based on observational surveys, the risk factors of CVD are rapidly increasing, both in Iranian adults [2] and adolescents [7]. A growing body of evidence suggests that CVD is affected by exposure factors in early life [8][9][10]. Human milk feeding is an important factor that has been associated with reduced CVD risks [11,12].…”

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