Effect of Glucocorticoid Administration Early in Life on Aortic Prostaglandin Synthesis and Morphology in Atherosclerosis-Susceptible Pigeons

Deitemeyer, D.; Yunker, R.L.; Ashraf, Muhammad; Subbiah, M.T.R.

doi:10.1055/s-0029-1210430

Cited by 4 publications

(6 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…, 2002). A single study in atherosclerosis‐susceptible pigeons suggested that glucocorticoid administration in early life influences aortic prostaglandin synthesis and morphology (Deitemeyer et al. , 1985).…”

Section: Glucocorticoids and Cardiovascular Pathophysiologymentioning

confidence: 99%

“…In female cynomologus monkeys, however, while depression increased sensitivity to negative feedback regulation of the HPA axis, it had no effect on atherogenesis or vascular function after prolonged exposure to a high-fat diet (Shively et al, 2002). A single study in atherosclerosissusceptible pigeons suggested that glucocorticoid administration in early life influences aortic prostaglandin synthesis and morphology (Deitemeyer et al, 1985). In cockerels, cortisone has been shown to both increase (Stamler et al, 1954) and reduce atheroma (Jain et al, 1965) (while cortisol had no effect).…”

Section: Cohort Studymentioning

confidence: 99%

“…Monkey (stress) Depression; impaired HPA feedback No effect on atherosclerosis (Shively et al, 2002) Pigeon Dexamethasone Reduced abnormalities in aortic ECs (Deitemeyer et al, 1985) Cockerel (fat-fed),…”

Section: Sample Design and Intervention Outcome Referencementioning

confidence: 99%

See 2 more Smart Citations

Therapeutic manipulation of glucocorticoid metabolism in cardiovascular disease

Hadoke

Iqbal

Walker

2009

British J Pharmacology

View full text Add to dashboard Cite

The therapeutic potential for manipulation of glucocorticoid metabolism in cardiovascular disease was revolutionized by the recognition that access of glucocorticoids to their receptors is regulated in a tissue-specific manner by the isozymes of 11b-hydroxysteroid dehydrogenase. Selective inhibitors of 11b-hydroxysteroid dehydrogenase type 1 have been shown recently to ameliorate cardiovascular risk factors and inhibit the development of atherosclerosis. This article addresses the possibility that inhibition of 11b-hydroxsteroid dehydrogenase type 1 activity in cells of the cardiovascular system contributes to this beneficial action. The link between glucocorticoids and cardiovascular disease is complex as glucocorticoid excess is linked with increased cardiovascular events but glucocorticoid administration can reduce atherogenesis and restenosis in animal models. There is considerable evidence that glucocorticoids can interact directly with cells of the cardiovascular system to alter their function and structure and the inflammatory response to injury. These actions may be regulated by glucocorticoid and/or mineralocorticoid receptors but are also dependent on the 11b-hydroxysteroid dehydrogenases which may be expressed in cardiac, vascular (endothelial, smooth muscle) and inflammatory (macrophages, neutrophils) cells. The activity of 11b-hydroxysteroid dehydrogenases in these cells is dependent upon differentiation state, the action of pro-inflammaotory cytokines and the influence of endogenous inhibitors (oxysterols, bile acids). Further investigations are required to clarify the link between glucocorticoid excess and cardiovascular events and to determine the mechanism through which glucocorticoid treatment inhibits atherosclerosis/restenosis. This will provide greater insights into the potential benefit of selective 11b-hydroxysteroid dehydrogenase inhibitors in treatment of cardiovascular disease.

show abstract

Section: Glucocorticoids and Cardiovascular Pathophysiologymentioning

confidence: 99%

Section: Cohort Studymentioning

confidence: 99%

See 1 more Smart Citation

Therapeutic manipulation of glucocorticoid metabolism in cardiovascular disease

Hadoke

Iqbal

Walker

2009

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…At 27-28 days gestation, half of the ewes were randomized to receive Dex (0.56 mg/kg) by continuous intravenous infusion over 48 h. Notably, maternal glucocorticoid-dosing guidelines were established by dose-ranging studies in sheep (20), and the early pregnancy exposure we utilized approximates the dose (but not the timing) of Dex used clinically before threatened preterm delivery (24 mg or ϳ0.5 mg/kg during the later stage of pregnancy). On a millgram per kilogram basis, the dose we utilized is lower than that used in other preclinical studies that have shown Dex-induced suppression of vascular PGE2 metabolism, including studies in rats (16) and pigeons (11). The timing of the exposure is designed to mimic the effects of maternal-fetal stressors that are operative early in pregnancy.…”

Section: Methodsmentioning

confidence: 99%

Impact of maternal dexamethasone on coronary PGE₂production and prostaglandin-dependent coronary reactivity

Roghair

Volk

Lamb

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Intrauterine growth restriction is associated with increased fetal glucocorticoid exposure and an increased risk of adult coronary artery disease. Coronary arteries from sheep exposed to early gestation dexamethasone (Dex) have increased constriction to angiotensin II (ANG II). Prostaglandin E(2) (PGE(2)) helps maintain coronary dilation, but PGE(2) production is acutely decreased by Dex administration. We hypothesized early gestation Dex exposure impairs adult coronary PGE(2) production with subsequent increases in coronary reactivity. Dex was administered to ewes at 27-28 days gestation (term 145 days). Coronary reactivity was assessed by wire myography in offspring at 4 mo of age (N = 5 to 7). Coronary smooth muscle cells were cultured and prostaglandin production was measured after 90 min incubation with radiolabeled arachidonate. Coronary myocytes from Dex-exposed lambs had a significant decrease in PGE(2) production that was reversed with ANG II incubation. Dex-exposed coronary arteries had increased constriction to ANG II and attenuated dilatation to arachidonic acid, with the greatest difference seen after the endothelium was inactivated by rubbing. Preincubation with the cyclooxygenase (COX) inhibitor indomethacin altered control responses and recapitulated the heightened coronary tone seen following Dex exposure. We conclude that impaired coronary smooth muscle COX-mediated PGE(2) production contributes to the coronary dysfunction elicited by early gestation Dex. Programmed inhibition of vasodilatory prostanoid production may link an adverse intrauterine environment with adult coronary artery disease.

show abstract

“…In contrast, animal studies suggest that glucocorticoids reduce atherosclerosis, despite causing hyperlipidaemia [30–40]. Furthermore, a recent report elegantly demonstrated that 'painting' dexamethasone onto atherosclerotic lesions improved markers of plaque stability (reducing macrophage content and increasing fibrous cap thickness) [41].…”

Section: Glucocorticoids and Cardiovascular Riskmentioning

confidence: 99%

Modulation of 11β-Hydroxysteroid Dehydrogenase as a Strategy to Reduce Vascular Inflammation

Hadoke

Kipari

Chapman

2013

Curr Atheroscler Rep

View full text Add to dashboard Cite

Atherosclerosis is a chronic inflammatory disease in which initial vascular damage leads to extensive macrophage and lymphocyte infiltration. Although acutely glucocorticoids suppress inflammation, chronic glucocorticoid excess worsens atherosclerosis, possibly by exacerbating systemic cardiovascular risk factors. However, glucocorticoid action within the lesion may reduce neointimal proliferation and inflammation. Glucocorticoid levels within cells do not necessarily reflect circulating levels due to pre-receptor metabolism by 11β-hydroxysteroid dehydrogenases (11β-HSDs). 11β-HSD2 converts active glucocorticoids into inert 11-keto forms. 11β-HSD1 catalyses the reverse reaction, regenerating active glucocorticoids. 11β-HSD2-deficiency/ inhibition causes hypertension, whereas deficiency/ inhibition of 11β-HSD1 generates a cardioprotective lipid profile and improves glycemic control. Importantly, 11β-HSD1-deficiency/ inhibition is atheroprotective, whereas 11β-HSD2-deficiency accelerates atherosclerosis. These effects are largely independent of systemic risk factors, reflecting modulation of glucocorticoid action and inflammation within the vasculature. Here, we consider whether evidence linking the 11β-HSDs to vascular inflammation suggests these isozymes are potential therapeutic targets in vascular injury and atherosclerosis.

show abstract

Effect of Glucocorticoid Administration Early in Life on Aortic Prostaglandin Synthesis and Morphology in Atherosclerosis-Susceptible Pigeons

Cited by 4 publications

References 4 publications

Therapeutic manipulation of glucocorticoid metabolism in cardiovascular disease

Therapeutic manipulation of glucocorticoid metabolism in cardiovascular disease

Impact of maternal dexamethasone on coronary PGE₂production and prostaglandin-dependent coronary reactivity

Modulation of 11β-Hydroxysteroid Dehydrogenase as a Strategy to Reduce Vascular Inflammation

Contact Info

Product

Resources

About

Effect of Glucocorticoid Administration Early in Life on Aortic Prostaglandin Synthesis and Morphology in Atherosclerosis-Susceptible Pigeons

Cited by 4 publications

References 4 publications

Therapeutic manipulation of glucocorticoid metabolism in cardiovascular disease

Therapeutic manipulation of glucocorticoid metabolism in cardiovascular disease

Impact of maternal dexamethasone on coronary PGE2production and prostaglandin-dependent coronary reactivity

Modulation of 11β-Hydroxysteroid Dehydrogenase as a Strategy to Reduce Vascular Inflammation

Contact Info

Product

Resources

About

Impact of maternal dexamethasone on coronary PGE₂production and prostaglandin-dependent coronary reactivity