Increased Elastic Tissue Defect Formation in the Growth Restricted Brown Norway Rat: A Potential Link Between In Utero Condition and Cardiovascular Disease

Pascoe, Katie; Wlodek, Mary E.; Jones, Gregory T.

doi:10.1203/pdr.0b013e3181761859

Cited by 8 publications

(7 citation statements)

References 33 publications

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“…Although increased elastin deposition may be counterintuitive in relation to increased stiffening, Arribas and colleagues (2008) showed that an increased deposition of abnormally organized elastin is associated with artery wall stiffening in blood vessels of spontaneous hypertensive rats even before the development of hypertension. Furthermore, our group has also shown that uteroplacental insufficiency was associated with increased internal elastic lamina defects in the aorta of male and female offspring (Pascoe et al 2008). Thus, if elastin is disorganized, these alterations in elastin may contribute to the vascular stiffness and narrowing of uterine arteries in Restricted females.…”

Section: Discussionmentioning

confidence: 88%

Uteroplacental insufficiency programs regional vascular dysfunction and alters arterial stiffness in female offspring

Mazzuca¹,

Wlodek²,

Dragomir

et al. 2010

The Journal of Physiology

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Intrauterine growth restriction caused by uteroplacental insufficiency increases the risk of cardiovascular disease in adulthood. Vascular mechanisms in female offspring are poorly understood. The aim of this study was to investigate the effects of uteroplacental insufficiency on blood pressure, vascular reactivity and arterial stiffness in four vascular beds in female offspring born growth restricted. Uteroplacental insufficiency was induced on day 18 of gestation in Wistar Kyoto rats by bilateral uterine vessel ligation (Restricted) or sham surgery (Controls). Wire and pressure myography were used to test endothelial and smooth muscle function, and passive mechanical wall properties, respectively, in uterine, mesenteric, renal and femoral arteries of 18-month-old female offspring. Collagen and elastin fibres were quantified using circular crossed-polarized light microscopy and quantitative real time polymerase chain reaction. Restricted female offspring were born 10-15% smaller. Restricted females were normotensive, had plasma triglycerides 2-fold elevated and had uterine endothelial dysfunction, attributed to a 23% reduction in the maximal relaxation produced by endothelium-derived hyperpolarizing factor. Uterine artery stiffness was increased, with an augmented proportion of thick and decreased proportion of thin collagen fibres. Vascular reactivity and mechanical wall properties were preserved in mesenteric, renal and femoral arteries in growth restricted females. Female offspring born growth restricted have selective uterine artery endothelial dysfunction and increased wall stiffness. The preserved vascular function in other arteries may explain the lack of hypertension in these females. The uterine artery specific dysfunction has potential implications for impaired pregnancy adaptations and a compromised intrauterine environment of the next generation.

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Section: Discussionmentioning

confidence: 88%

Uteroplacental insufficiency programs regional vascular dysfunction and alters arterial stiffness in female offspring

Mazzuca¹,

Wlodek²,

Dragomir

et al. 2010

The Journal of Physiology

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“…In sheep, aortic vascular remodeling was associated with increased collagen (100) and reduced elastin content that was vascular bed specific as no changes were observed in the superior mesenteric artery (401). An increased occurrence of aortic internal elastic lamina defects was also observed in offspring of bilateral uterine artery ligation rats (299). Vascular remodeling has been observed in the pulmonary arteries, where maternal nutrient restriction led to increased smooth muscle thickness following acute (240) or chronic (375,445) exposure of the offspring to hypoxia.…”

Section: Vascular Remodelingmentioning

confidence: 95%

“…An increased number of smooth muscle cells, however, might not necessarily reflect improved constrictor capacity if the components of the cell were disrupted or malformed. Indeed, some of the vascular remodeling work has shown that an increased number of defects were observed in the elastic lamina layers (299). Furthermore, vascular stiffness was shown to be increased as a result of increased collagen content, and this could hinder the flexibility of the vessel both in terms of vasodilation and vasoconstriction; therefore, both increased and decreased responses to KCl could be equally indicative of vascular dysfunction following a compromised pregnancy.…”

Section: Vasoconstrictor Mechanismsmentioning

confidence: 99%

In Utero Origins of Hypertension: Mechanisms and Targets for Therapy

Morton

Cooke

Davidge³

2016

Physiological Reviews

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The developmental origins of health and disease theory is based on evidence that a suboptimal environment during fetal and neonatal development can significantly impact the evolution of adult-onset disease. Abundant evidence exists that a compromised prenatal (and early postnatal) environment leads to an increased risk of hypertension later in life. Hypertension is a silent, chronic, and progressive disease defined by elevated blood pressure (>140/90 mmHg) and is strongly correlated with cardiovascular morbidity/mortality. The pathophysiological mechanisms, however, are complex and poorly understood, and hypertension continues to be one of the most resilient health problems in modern society. Research into the programming of hypertension has proposed pharmacological treatment strategies to reverse and/or prevent disease. In addition, modifications to the lifestyle of pregnant women might impart far-reaching benefits to the health of their children. As more information is discovered, more successful management of hypertension can be expected to follow; however, while pregnancy complications such as fetal growth restriction, preeclampsia, preterm birth, etc., continue to occur, their offspring will be at increased risk for hypertension. This article reviews the current knowledge surrounding the developmental origins of hypertension, with a focus on mechanistic pathways and targets for therapeutic and pharmacologic interventions.

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“…These findings are more characteristic of atherogenic vascular remodelling rather than the vascular structural matrix changes associated with abnormal arterial stiffness [84]. Other studies of rat RUPP offspring have also identified an increased propensity to develop arterial internal elastic lamina lesions, an early atherosclerotic process, when studied at 8 and 16 weeks of age [64]. …”

Section: Mechanism Of Long-term Programing? the Cardiovascular Systemmentioning

confidence: 99%

Pre-eclampsia and offspring cardiovascular health: mechanistic insights from experimental studies

et al. 2012

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Pre-eclampsia is increasingly recognized as more than an isolated disease of pregnancy. Women who have had a pregnancy complicated by pre-eclampsia have a 4-fold increased risk of later cardiovascular disease. Intriguingly, the offspring of affected pregnancies also have an increased risk of higher blood pressure and almost double the risk of stroke in later life. Experimental approaches to identify the key features of pre-eclampsia responsible for this programming of offspring cardiovascular health, or the key biological pathways modified in the offspring, have the potential to highlight novel targets for early primary prevention strategies. As pre-eclampsia occurs in 2–5% of all pregnancies, the findings are relevant to the current healthcare of up to 3 million people in the U.K. and 15 million people in the U.S.A. In the present paper, we review the current literature that concerns potential mechanisms for adverse cardiovascular programming in offspring exposed to pre-eclampsia, considering two major areas of investigation: first, experimental models that mimic features of the in utero environment characteristic of pre-eclampsia, and secondly, how, in humans, offspring cardiovascular phenotype is altered after exposure to pre-eclampsia. We compare and contrast the findings from these two bodies of work to develop insights into the likely key pathways of relevance. The present review and analysis highlights the pivotal role of long-term changes in vascular function and identifies areas of growing interest, specifically, response to hypoxia, immune modification, epigenetics and the anti-angiogenic in utero milieu.

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Increased Elastic Tissue Defect Formation in the Growth Restricted Brown Norway Rat: A Potential Link Between In Utero Condition and Cardiovascular Disease

Cited by 8 publications

References 33 publications

Uteroplacental insufficiency programs regional vascular dysfunction and alters arterial stiffness in female offspring

Uteroplacental insufficiency programs regional vascular dysfunction and alters arterial stiffness in female offspring

In Utero Origins of Hypertension: Mechanisms and Targets for Therapy

Pre-eclampsia and offspring cardiovascular health: mechanistic insights from experimental studies

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