Intrauterine growth restriction promotes vascular remodelling following carotid artery ligation in rats.
ABSTRACT Epidemiological studies revealed an association between IUGR (intrauterine growth restriction) and an increased risk of developing CVDs (cardiovascular diseases), such as atherosclerosis or hypertension, in later life. Whether or not IUGR contributes to the development of atherosclerotic lesions, however, is unclear. We tested the hypothesis that IUGR aggravates experimentally induced vascular remodelling. IUGR was induced in rats by maternal protein restriction during pregnancy (8% protein diet). To detect possible differences in the development of vascular injury, a model of carotid artery ligation to induce vascular remodelling was applied in 8-week-old intrauterine-growth-restricted and control rat offspring. Histological and immunohistochemical analyses were performed in the ligated and non-ligated carotid arteries 8 weeks after ligation. IUGR alone neither caused overt histological changes nor significant dedifferentiation of VSMCs (vascular smooth muscle cells). After carotid artery ligation, however, neointima formation, media thickness and media/lumen ratio were significantly increased in rats after IUGR compared with controls. Moreover, dedifferentiation of VSMCs and collagen deposition in the media were more prominent in ligated carotids from rats after IUGR compared with ligated carotids from control rats. We conclude that IUGR aggravates atherosclerotic vascular remodelling induced by a second injury later in life.
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ABSTRACT: Embryonic and fetal growth depend on genetic and environmental factors, and the process is the result of the interaction between these factors. About 7-9% of live-born infants have a birth weight below normal (below the 10th percentile). The rate and extent of intrauterine growth restriction (IUGR) varies by ethnicity and socio-economic status. Some of the suspected causes of IUGR are as follows. (1) Maternal factors such as inadequate or severe malnutrition, chronic maternal diseases, birth order, multiple births, and parental genetic factors. (2) Placental pathology, mainly placental vascular damage that may lead to placental insufficiency. This is often found in maternal diseases such as pre-eclampsia, and Thrombophilia. (3) Intrauterine infections and specific fetal syndromes, including chromosomal aberrations. (4) Non-classified causes such as adolescent's pregnancy, maternal smoking and alcohol drinking, living at high altitudes. Several existing animal models for IUGR, including uterine artery ligation or gene knock out models, although insightful of potential mechanism(s) underlying intrauterine growth restriction, are limited in that they do not reflect human causality. As the ultimate goal is prevention, we seem still to be distant from achieving this goal.Reproductive Toxicology 01/2005; 20(3):301-22. · 3.14 Impact Factor
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ABSTRACT: Intimal smooth muscle (SMC) proliferation was examined in the rat left carotid in regions lacking endothelium for prolonged periods of time. Arteries of animals injected with tritiated thymidine and Evans blue were examined at intervals between 0 and 12 weeks. The endothelial layer was regenerated from the ends of the denuded segment but failed to cover the central third of the artery by 12 weeks. Autoradiography on samples from this central region (stained blue) and the endothelialized ends (white) showed that SMC proliferation reached a maximum at 48 hours in the media (46%) and at 96 hours in the intima (73%). Subsequently, the thymidine index declined to baseline (0.06%) by 4 weeks throughout the media and by 8 weeks in the intima covered by endothelium. SMC proliferation persisted at a high level (3.8%) at the surface of the intima lacking endothelium even at 12 weeks. Despite continued proliferation of luminal SMC, total arterial SMC number was the same at 2 and 12 weeks. These results support the concept that intimal SMC proliferation after arterial injury is an acute event related to the initial injury process. Persistent proliferation of luminal SMC does not result in an increase in intimal cell number.Laboratory Investigation 10/1983; 49(3):327-33. · 3.96 Impact Factor
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ABSTRACT: Smooth muscle cells (SMCs) of rabbit aorta undergo marked changes in myosin isoform content during development. Analysis of nonmuscle myosin composition at the protein level has permitted the identification of three phases in the SMC differentiation process: fetal, postnatal, and adult. Using monoclonal antibodies specific for smooth muscle and nonmuscle myosins and extra domain A of fibronectin as well as cDNA probes for platelet-derived growth factors (PDGF) and various procollagens, we have evaluated the differentiation pattern of aortic SMCs in two-kidney, one-clip hypertensive rabbits. Morphometric and bromo-deoxyuridine studies indicate that hypertrophy of aortic media along with intimal thickening occurring in hypertensive animals is due to SMC hyperplasia. Western blotting experiments performed on aortic specimens from hypertensive animals with antimyosin antibodies revealed the appearance of a myosin isoform pattern of the "immature" type. Immunofluorescence tests showed that these cells are localized in the thickened intima or distributed in the underlying media (sparsely or in groups). Similarly, the fibronectin variant showing the extra domain A, peculiar to "phenotypically modulated" SMCs, appeared in intimal thickening, and its expression followed the time course of nonmuscle myosin expression. Counting of postnatal-type SMCs in the aortic media revealed that this cell population increases markedly with hypertension (2- up to 15-fold at 4 months) and then declines to near control level in 8-month hypertensive rabbits. Diminution of postnatal-type SMCs at later stages of hypertension was temporally correlated with the slowing down of aortic wall hypertrophy. Average levels of mRNAs, as determined by densitometric analysis in aortas from 1- and 2.5-month hypertensive rabbits, showed an increased expression for PDGF beta receptor (up to twofold), procollagen type I (alpha 1, threefold), procollagen type III (alpha 1, twofold), and fibronectin (up to threefold) compared with controls. Conversely, the steady-state levels of mRNAs for PDGF (A and B chain), PDGF alpha receptor, TGF-beta 1, and procollagen type IV (alpha 1) did not increase significantly. These results provide evidence that in adult renovascular hypertensive rabbits, the hyperplastic growth of aortic SMCs is accompanied by the expansion of an "immature" cell phenotype characteristic of the early stages of development.Circulation Research 06/1994; 74(5):774-88. · 11.86 Impact Factor