the effect of maternal dietary restriction on the elastic … cvs 7 nov 08.pdf · 2011-09-29 ·...
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Hertfortshire, England
The birth and death records of nearly 16,000 individuals born
showed that death rates from Cardiovascular disease (CVD) fell
progressively between the low and high birth weight groups.
Osmond C, Barker DJP, Winter PD, Fall CHD, Simmonds J. Early growth and death from cardiovascular disease in women. BMJ 1993;307: 1519-24.
Sheffield, England
Standardized mortality ratios for CVD fell from 119 in men who
weighed 5.5 pounds or less at birth to 74 in men who weighed
more than 8.5 pounds.
Barker DJP, Osmond C, Simmonds SJ, Wield GA. The relation of small head
circumference and thinness at birth to death from cardiovascular disease in adult life. BMJ 1993; 306:422-6
In India,
Among 517 men and women, low birth weight, short
birth length, and small head circumference at birth
were associated with a raised prevalence of CVD.
Stein CE, Fall CHD, Kumaran K, Osmond C, Cox V, Barker DJP. Fetal growth and coronary heart disease in South India. Lancet 1996;348:1478-80.
Intrauterine programming of coronary
heart disease and stroke.
Barker DJ, Acta Paediatr Suppl 1997; 423: 178-182
The fetal origins of coronary heart disease
and non-insulin dependent diabetes in
India. Fall, C.H., and Barker, D.J. Indian Pediatr 1997; 34, 5-8.
Impaired fetal growth and atherosclerosis of
carotid and peripheral arteries.
Martyn CN, Gale CR, Jespersen S, Sherriff SB. Lancet 1998; 352(9123):
173-178. Barker DJ, Clark PM. Rev Reprod 1997; 2(2): 105-112
The fetal origins of hypertension.
Barker DJ, Martyn CN. Adv Nephrol Necker Hosp 1997; 26: 65-72.
Swedish study of 149,378 boys showed that
systolic blood pressure fell by 0.8 mmHg for
every 1 kg increase in birth weight
Nilsson, P.M., Ostergren, P.O., Nyberg, P., Soderstrom, M., and Allebeck,
P. (1997). J Hypertens 15, 1627-1631.
A review of 80 studies of the relationship
between systolic blood pressure and birth
weight in 444,000 males and females of
various races, aged 0-84 years, found that
blood pressure fell approximately 2 mmHg/kg
with increasing birth weight
Huxley, R.R., Shiell, A.W., and Law, C.M. (2000). J Hypertens 18, 815-831.
The process whereby a stimulus at a
critical period of the development leads
to persistent changes in structure,
physiology and metabolism
physiological and molecular mechanisms
which lead to fetal “programming” of
the cardiovascular system are unknown
Impaired synthesis of elastin in the walls of
the aorta and large conduit arteries during
early development may be an initiating
event in the pathogenesis of systemic
hypertension.
Lancet 1997; 350: 953-955.
Berry, C.L., Looker, T., and Germain, J. (1972). The growth and development of the rat aorta. I. Morphological aspects. J Anat 113, 1-16.
the elastin : collagen ratio
in the rabbit aorta = the pulmonary artery
By the age of 2 months,
pulmonary pressure 15 mmHg
systemic blood pressure 40-80 mmHg
the elastin : collagen ratio in the aorta is > in the pulmonary artery
1.75 times
At birth,
Leung DYM, Glagov S, Mathews MB. A new in vitro system for studying cell response to
mechanical stimulation. Different effects of cyclic stretching and agitation on smooth muscle cell biosynthesis. Exp Cell Res 1977; 109: 285-298.
Avolio A, et.al., Quantification of alterations in structure and function of elastin in the arterial media. Hypertension 1998, 32:170-175.
A B
A) a 15-year-old tiger(505 million cycles)
B) a 15-year-old jaguarundi(1025 million cycles)
Izzo, J.L., Jr., and Shykoff, B.E. (2001). Arterial stiffness: clinical relevance,
measurement, and treatment. Rev Cardiovasc Med 2, 29-34, 37-40.
0.2
0.5
0.7
1.0
1.2
1.5
Ep (Nm-2 x 105)
0 50 100 150 200 250
Pressure (mmH)
In rats aged 4
weeks, whose
mothers were fed
a low-protein diet
during pregnancy
show that their
aortas are stiffer
than controls
born to mothers fed a normal diet
Functional stiffness (Ep)
The values of functional elastic modulus
Material stiffness (Einc)
The circumferential incremental elastic modulus
R
PRE p
Rh
PREinc
75.0
The aim of this study was to test the
hypothesis that the impairment of elastin
synthesis during a critical period of blood
vessel development, which leads to
permanent changes in arterial
mechanical properties, may be a
mechanism for the association between
growth restriction in utero, raised arterial stiffness in adulthood.
Female Wistar rats were fed a diet containing 9% casein two weeks before mating, throughout their pregnancy and during weaning for 3 weeks.
An isocaloric diet containing 18% casein was fed to a similar number of pregnant rats
[Langley-Evans et al., 1994] ; both diets were obtained from Hoppe Farms, Woerden, Netherlands
The offspring (8 Males & 8 Females/ diet group (LP, NP)/ aged group)
4, 6, 8, 12, 20, 50 weeks of age
Were sacrificed
Arterial elasticity measurement
0
1
2
3
4
5
6
7
Female Male
Bir
th
weig
ht [
g]
LP group NP group
** **
0
100
200
300
400
500
600
700
800
0 50 100 150 200 250 300 350 400
Age [days]
Bo
dy w
eig
ht
[g]
Female [LP] Female [NP] Male [LP] Male [NP]
Abdominal aorta at 4 weeks of age
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
0 50 100 150 200 250 300
Pressure (mmHg)
Fu
ncti
on
al m
od
ulu
s (
Nm
-2 x
10
6)
Female [LP] Female [NP] Male [LP] Male [NP]
Abdominal aorta at 50 weeks of age
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0 50 100 150 200 250 300
Pressure (mmHg)
Fu
ncti
on
al m
od
ulu
s (
Nm
-2 x
10
6)
Female [LP] Female [NP] Male [LP] Male [NP]
Thoracic aorta at 4 weeks of age
0
0.1
0.2
0.3
0.4
0.5
0.6
0 50 100 150 200 250 300
Pressure (mmHg)
Fu
ncti
on
al m
od
ulu
s (
Nm
-2 x
10
6)
Female [LP] Female [NP] Male [LP] Male [NP]
Thoracic aorta at 50 weeks of age
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
0.4
0.45
0.5
0 50 100 150 200 250 300
Pressure (mmHg)
Fu
ncti
on
al m
od
ulu
s (
Nm
-2 x
10
6)
Female [LP] Female [NP] Male [LP] Male [NP]
Abdominal aorta
20
40
60
80
100
120
140
0 10 20 30 40 50 60
Age [weeks]
Ep
[N
m-2 x
10
3]
Female [LP] Female [NP] Male [LP] Male [NP]
Thoracic aorta
20
30
40
50
60
70
80
0 10 20 30 40 50 60
Age [weeks]
Ep
[N
m-2 x
10
3]
Female [LP] Female [NP] Male [LP] Male [NP]
Abdominal aorta at 4 weeks of age
0
1
2
3
4
5
6
7
1 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9
Relative radius
Incre
men
tal m
od
ulu
s (
Nm
-2 x
10
6)
Female [LP] Female [NP] Male [LP] Male [NP]
Abdominal aorta at 50 weeks of age
0
1
2
3
4
5
6
7
1 1.2 1.4 1.6 1.8 2 2.2
Relative radiusIn
cre
men
tal m
od
ulu
s (
Nm
-2 x
10
6)
Female [LP] Female [NP] Male [LP] Male [NP]
Thoracic aorta at 4 weeks of age
0
1
2
3
4
5
6
1 1.2 1.4 1.6 1.8 2
Relative radius
Increm
en
tal m
od
ulu
s (
Nm
-2 x
10
6)
Female [LP] Female [NP] Male [LP] Male [NP]
Thoracic aorta at 50 weeks of age
0
1
2
3
4
5
6
7
8
1 1.2 1.4 1.6 1.8 2 2.2 2.4
Relative radius
Incre
men
tal m
od
ulu
s (
Nm
-2 x
10
6)
Female [LP] Female [NP] Male [LP] Male [NP]
Abdominal aorta
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
2
0 10 20 30 40 50 60
Age [weeks]
Incre
men
tal m
od
ulu
s (
Nm
-2 x
10
6)
Female [LP] Female [NP] Male [LP] Male [NP]
Thoracic aorta
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
0 10 20 30 40 50 60
Age [weeks]
Incre
men
tal m
od
ulu
s (
Nm
-2 x
10
6)
Female [LP] Female [NP] Male [LP] Male [NP]
The results showed that offspring
whose mothers were fed a low protein
diet had lower birthweight than their control counterparts whose mothers were fed a normal protein diet
The functional stiffness of the thoracic
aorta in LP animals (after puberty) was greater than that of controls whereas the
material stiffness was not much affected by growth restriction. The changes in
stiffness with age were similar in LP and
NP animals with a decrease in both
structural and functional stiffness between the ages of 4 and 20 weeks.
The elasticity data obtained to
date does not support the
hypothesis that growth restriction
causes impairment of elastin
synthesis leading to increased
stiffness of the walls of the elastic arteries
Zambian children aged 5-9:
› it was found that those with the lowest birth
weight do indeed have higher systolic
pressure and stiffer femoral arteries than
those with the highest birth weights
Mutiti A, Kelly MP, Greenwald SE. Nutritional status and arterial stiffness in Zambian
children. 4th International Congress of the African Association of Physiological Science, Tetouan, Morocco; 2004
Skilton et al. reported that newborn
human babies with IUGR had a thicker
aortic wall than normal
Skilton, M.R., Evans, N., Griffiths, K.A., Harmer, J.A., and Celermajer, D.S. (2005). Aorticwall thickness in newborns with intrauterine growth restriction. Lancet 365, 1484-1486.
It is commonly agreed that the control of
blood pressure is mediated and influenced
by multiple structural, neural, endocrine,
and renal mechanisms.
As well as mechanisms in which
programming lifelong cardiovascular
function may act together or
independently. Thus, perturbations in
one control mechanism inevitably
lead to compensatory changes in
others and dissecting out those which are primary is likely to be difficult
• Professor SE Greenwald
• Professor Jo Martin
• ICMS staff (Pathology group):
Alex Brown, Carol Nickols, and Chris
Evagora
• Dr. Upa Kukongviriyapan and
• Saowanee Luangaram
• BSc students; Pira Saravanamuthu,
Dominic Greenyer, and Madiha Ahmed
• Thai government.
• Anatomy, KKU staff
• My family
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