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Early and late postnatal myocardial and vascular changes in a protein restriction rat model of intrauterine growth restriction.

Menendez-Castro C, Fahlbusch F, Cordasic N, Amann K, Münzel K, Plank C, Wachtveitl R, Rascher W, Hilgers KF, Hartner A - PLoS ONE (2011)

Bottom Line: The offspring was reduced to six males per litter.At day 70 the expression of osteopontin was induced 7.2-fold.A 3- to 7-fold increase in the expression of the profibrotic cytokines TGF-β and CTGF as well as of microfibrillar matrix molecules was observed.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics and Adolescent Medicine, University of Erlangen-Nürnberg, Erlangen, Germany. carlos.menendez-castro@uk-erlangen.de

ABSTRACT
Intrauterine growth restriction (IUGR) is a risk factor for cardiovascular disease in later life. Early structural and functional changes in the cardiovascular system after IUGR may contribute to its pathogenesis. We tested the hypothesis that IUGR leads to primary myocardial and vascular alterations before the onset of hypertension. A rat IUGR model of maternal protein restriction during gestation was used. Dams were fed low protein (LP; casein 8.4%) or isocaloric normal protein diet (NP; casein 17.2%). The offspring was reduced to six males per litter. Immunohistochemical and real-time PCR analyses were performed in myocardial and vascular tissue of neonates and animals at day 70 of life. In the aortas of newborn IUGR rats expression of connective tissue growth factor (CTGF) was induced 3.2-fold. At day 70 of life, the expression of collagen I was increased 5.6-fold in aortas of IUGR rats. In the hearts of neonate IUGR rats, cell proliferation was more prominent compared to controls. At day 70 the expression of osteopontin was induced 7.2-fold. A 3- to 7-fold increase in the expression of the profibrotic cytokines TGF-β and CTGF as well as of microfibrillar matrix molecules was observed. The myocardial expression and deposition of collagens was more prominent in IUGR animals compared to controls at day 70. In the low-protein diet model, IUGR leads to changes in the expression patterns of profibrotic genes and discrete structural abnormalities of vessels and hearts in adolescence, but, with the exception of CTGF, not as early as at the time of birth. Invasive and non-invasive blood pressure measurements confirmed that IUGR rats were normotensive at the time point investigated and that the changes observed occurred independently of an increased blood pressure. Hence, altered matrix composition of the vascular wall and the myocardium may predispose IUGR animals to cardiovascular disease later in life.

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Body and relative heart weights.A: Birth weights, B: body weights at day 70 of life and C: relative heart weights at day 70 of life of rats with intrauterine growth restriction (LP) and their respective controls (NP). Data are means±sem.
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pone-0020369-g001: Body and relative heart weights.A: Birth weights, B: body weights at day 70 of life and C: relative heart weights at day 70 of life of rats with intrauterine growth restriction (LP) and their respective controls (NP). Data are means±sem.

Mentions: Low protein diet in the pregnant dams led to a significant reduction of birth weights of their offspring (figure 1A). Some degree of catch up growth was observed in the protein restricted offspring (LP). However, at day 70 of life, body weights of LP animals were still reduced compared to the body weights of the control group (NP) (figure 1B). Relative heart weights at day 70 of life were comparable in NP and LP (figure 1C). Systolic blood pressure was comparable in the LP and NP group as assessed by tail cuff blood pressure measurements performed in 70 days old rats (134.5±7.03 mmHg in NP versus 127.3±5.03 mmHg in LP, n.s.). Moreover, intraarterial blood pressure recordings revealed no differences in mean arterial blood pressure levels of NP and LP rats at this age (105.3±4.63 mmHg in NP versus 101.3±7.12 mmHg in LP, n.s.). These findings were confirmed by telemetric blood pressure measurements in two rats of each experimental group from day 70 for one week (Figure 2).


Early and late postnatal myocardial and vascular changes in a protein restriction rat model of intrauterine growth restriction.

Menendez-Castro C, Fahlbusch F, Cordasic N, Amann K, Münzel K, Plank C, Wachtveitl R, Rascher W, Hilgers KF, Hartner A - PLoS ONE (2011)

Body and relative heart weights.A: Birth weights, B: body weights at day 70 of life and C: relative heart weights at day 70 of life of rats with intrauterine growth restriction (LP) and their respective controls (NP). Data are means±sem.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3105022&req=5

pone-0020369-g001: Body and relative heart weights.A: Birth weights, B: body weights at day 70 of life and C: relative heart weights at day 70 of life of rats with intrauterine growth restriction (LP) and their respective controls (NP). Data are means±sem.
Mentions: Low protein diet in the pregnant dams led to a significant reduction of birth weights of their offspring (figure 1A). Some degree of catch up growth was observed in the protein restricted offspring (LP). However, at day 70 of life, body weights of LP animals were still reduced compared to the body weights of the control group (NP) (figure 1B). Relative heart weights at day 70 of life were comparable in NP and LP (figure 1C). Systolic blood pressure was comparable in the LP and NP group as assessed by tail cuff blood pressure measurements performed in 70 days old rats (134.5±7.03 mmHg in NP versus 127.3±5.03 mmHg in LP, n.s.). Moreover, intraarterial blood pressure recordings revealed no differences in mean arterial blood pressure levels of NP and LP rats at this age (105.3±4.63 mmHg in NP versus 101.3±7.12 mmHg in LP, n.s.). These findings were confirmed by telemetric blood pressure measurements in two rats of each experimental group from day 70 for one week (Figure 2).

Bottom Line: The offspring was reduced to six males per litter.At day 70 the expression of osteopontin was induced 7.2-fold.A 3- to 7-fold increase in the expression of the profibrotic cytokines TGF-β and CTGF as well as of microfibrillar matrix molecules was observed.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics and Adolescent Medicine, University of Erlangen-Nürnberg, Erlangen, Germany. carlos.menendez-castro@uk-erlangen.de

ABSTRACT
Intrauterine growth restriction (IUGR) is a risk factor for cardiovascular disease in later life. Early structural and functional changes in the cardiovascular system after IUGR may contribute to its pathogenesis. We tested the hypothesis that IUGR leads to primary myocardial and vascular alterations before the onset of hypertension. A rat IUGR model of maternal protein restriction during gestation was used. Dams were fed low protein (LP; casein 8.4%) or isocaloric normal protein diet (NP; casein 17.2%). The offspring was reduced to six males per litter. Immunohistochemical and real-time PCR analyses were performed in myocardial and vascular tissue of neonates and animals at day 70 of life. In the aortas of newborn IUGR rats expression of connective tissue growth factor (CTGF) was induced 3.2-fold. At day 70 of life, the expression of collagen I was increased 5.6-fold in aortas of IUGR rats. In the hearts of neonate IUGR rats, cell proliferation was more prominent compared to controls. At day 70 the expression of osteopontin was induced 7.2-fold. A 3- to 7-fold increase in the expression of the profibrotic cytokines TGF-β and CTGF as well as of microfibrillar matrix molecules was observed. The myocardial expression and deposition of collagens was more prominent in IUGR animals compared to controls at day 70. In the low-protein diet model, IUGR leads to changes in the expression patterns of profibrotic genes and discrete structural abnormalities of vessels and hearts in adolescence, but, with the exception of CTGF, not as early as at the time of birth. Invasive and non-invasive blood pressure measurements confirmed that IUGR rats were normotensive at the time point investigated and that the changes observed occurred independently of an increased blood pressure. Hence, altered matrix composition of the vascular wall and the myocardium may predispose IUGR animals to cardiovascular disease later in life.

Show MeSH
Related in: MedlinePlus