Formation of intimal cushions in the ductus arteriosus as a model for vascular intimal thickening. An immunohistochemical study of changes in extracellular matrix components

Slomp, J.; Munsteren, J. Conny van; Poelmann, Robert E.; Reeder, E.G. de; Bogers, A. J. J. C.; Groot, Adriana C. Gittenberger‐de

doi:10.1016/0021-9150(92)90197-o

Cited by 84 publications

(69 citation statements)

References 30 publications

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“…PCNA-positive cells were randomly distributed in the wall of the DA in the present study, and intimal formation was not observed in the DA wall. These findings was in good agreement with the report of Slomp et al [27] that they observed intimal formation in humans and dogs, but not in rats.…”

Section: Discussionsupporting

confidence: 93%

Smooth Muscle Cell Proliferation in the Ductus Arteriosus and the Descending Aorta, and Effects of Enalapril on SMC Proliferation in Perinatal Rats.

Takizawa

Kawahata

Ikeda

et al. 1999

The Journal of Veterinary Medical Science

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ABSTRACT. This study was carried out to determine the proliferation profile of the smooth muscle cells (SMC) in the media of the ductus arteriosus (DA) and the descending aorta (Ao), and to examine the effects of the angiotensin-converting enzyme inhibitor enalapril on the proliferation of these cells in perinatal rats. The proliferating cell nuclear antigen (PCNA) index of the DA peaked in 19-day-old fetuses at 75%, and the index significantly declined in 20-day-old fetuses. The PCNA index of the Ao showed a similar profile until pups reached 1 day of age; however, the index of the Ao then increased in 3-day-old pups. The PCNA indices of the DA and Ao decreased significantly after maternal oral treatment with enalapril (10 mg/kg for 7 days), with a more marked decline in the DA than in the Ao. The PCNA indices of these vessels in 20-day-old fetuses were not altered by maternal treatment with enalapril. These results indicate that the SMC proliferation rate in the DA was similar to that in the Ao until pups reached the age of 1 day, and that the inhibitory effect of enalapril on the SMC proliferation was age-dependent and more prominent in the DA than in the Ao.-KEY WORDS: ductus arteriosus, enalapril, PCNA, proliferation, SMC.J. Vet. Med. Sci. 61(11): 1215-1218, 1999 investigated the PCNA labeling index to monitor the proliferating activity of the SMC, and we compared the effects of enalapril on SMC proliferation in the DA and the descending aorta (Ao). MATERIALS AND METHODSFemale Crj: Wistar rats, 10-12 weeks old at the time of mating, were used. They were maintained with commercial rat chow (CE-2, Clea Japan, Tokyo) and tap water ad libitum, and kept in a room at a temperature of 22 ± 3°C with a relative humidity of 55 ± 10%. Three females were placed with a male overnight, and were examined the next morning for the presence of sperm in a vaginal smear. The day when sperm was found was designated as day 0 of gestation, and the females were caged individually thereafter.To examine the age-related changes of the PCNA labeling indices of the DA and the Ao, fetuses were quickly removed from the uteri of mother rats from day 18 to day 21 of gestation, and 1 or 3 day-old newborn pups were obtained from witnessed deliveries. To examine the effect of enalapril on the PCNA labeling indices of these vessels, fetuses were obtained on day 19 or 20 of gestation from pregnant rats and were transplacentally administered enalapril (10 mg/kg) from day 12 or 13 for 7 consecutive days.Fetuses and newborn pups were decapitated, and then the thoracic cavity was opened and immersed in fresh fixative fluid. Fixation was performed in 100% ethanol for 24 hr, and the fixed materials were then freed of alcohol by treatment with xylene, embedded in Paraplast (Sherwood Closure of the ductus arteriosus (DA) is one of the most critical events for adaptation of mammals to extrauterine life. The ductal closure after birth occurs in two stages, i.e., initial closure and anatomical closure. Initial closure is brought about by contraction of th...

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Section: Discussionsupporting

confidence: 93%

Smooth Muscle Cell Proliferation in the Ductus Arteriosus and the Descending Aorta, and Effects of Enalapril on SMC Proliferation in Perinatal Rats.

Takizawa

Kawahata

Ikeda

et al. 1999

The Journal of Veterinary Medical Science

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“…In the human fetus, intimal cushions form in the subendothelial region, or the neointimal zone, during the last third of gestation (Gittenberger-de Groot et al, 1995) and are thought to be a necessary precursor for proper DA closure (De Reeder et al, 1990;Slomp et al, 1992;Gittenberger-de Groot et al, 1995). Human DA studies have found that there is a positive correlation between endothelial cell detachment from the IEL and smooth muscle cell migration into the neointimal zone once intimal cushion formation has occurred (De Reeder et al, 1990).…”

Section: Morphological Changesmentioning

confidence: 99%

Morphological Changes in the Chicken Ductus Arteriosi During Closure at Hatching

Belanger¹,

Copeland²,

Muirhead³

et al. 2008

The Anatomical Record

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The chicken embryo has two functioning ductus arteriosi (DA) during development. These blood vessels connect the pulmonary arteries to the descending aorta providing a right-to-left shunt of blood away from the nonrespiring lungs and to the systemic circuit and chorioallanotic membrane. The DA consists of two distinct tissue types along its length, a muscular proximal portion and an elastic distal portion. During hatching, the DA must close for proper separation of systemic and pulmonary circulation. We examined the morphological changes of the chicken DA before, during, and after hatching. Occlusion of the proximal DA began during external pipping and was complete at hatching. Anatomical remodeling began as early as external pipping with fragmentation of the internal elastic lamina and smooth muscle actin appearing in the neointimal zone. By day 2 posthatch, the proximal DA lumen was fully occluded by endothelial cells and smooth muscle actin positive cells. In contrast, the distal DA was not fully occluded by day 2 posthatch. Increases in Po 2 of the blood serves as the main stimulus for closure of the mammalian DA. The responsiveness of the chicken proximal DA to oxygen increased during hatching, peaking during external pipping. This peak correlated with an increase in blood gas Po 2 and the initial occlusion of the vessel. The distal portion remained unresponsive to oxygen throughout hatching. In conclusion, the chicken DA begins to close during external pipping when arterial Po 2 increases and vessel tone is most sensitive to oxygen.

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“…The reduced elasticity of the DA wall may help its structure collapse easily as a prelude to postnatal permanent closure of the DA. In PDA, in contrast, an abundance of elastin lamellae in the intima, a subendothelial elastic lamina, and a failure of intimal SMC migration are found in humans and animal models (de Reeder, 1990;Hinek, 1991;Slomp, 1992). In humans and in animal models such as canine puppies and the inbred Brown-Norway (BN) rat (Bokenkamp, 2006), the subendothelial elastic lamina is thought to limit the passage of SMCs from the media to the intima.…”

Section: Extracellular Matrix Involved In Vascular Remodelling Of the Damentioning

confidence: 99%

Recent Advances Concerning the Molecular Mechanism of Patent Ductus Arteriosus

Minamisawa¹,

Yokoyama²

2012

Congenital Heart Disease - Selected Aspects

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Formation of intimal cushions in the ductus arteriosus as a model for vascular intimal thickening. An immunohistochemical study of changes in extracellular matrix components

Cited by 84 publications

References 30 publications

Smooth Muscle Cell Proliferation in the Ductus Arteriosus and the Descending Aorta, and Effects of Enalapril on SMC Proliferation in Perinatal Rats.

Smooth Muscle Cell Proliferation in the Ductus Arteriosus and the Descending Aorta, and Effects of Enalapril on SMC Proliferation in Perinatal Rats.

Morphological Changes in the Chicken Ductus Arteriosi During Closure at Hatching

Recent Advances Concerning the Molecular Mechanism of Patent Ductus Arteriosus

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