Maternal stress and development of atherosclerosis in the adult apolipoprotein E-deficient mouse offspring.
Stress is a risk factor for cardiovascular disease, such as atherosclerosis. Stress during pregnancy (maternal stress) may have long-term consequences for the health of the offspring. However, it is not known whether maternal stress affects the offspring's predisposition to develop atherosclerosis. Atherosclerosis is often related to vascular endothelial dysfunction. We hypothesized that maternal stress affects vascular endothelial function and accelerates development of atherosclerosis in offspring of apolipoprotein E-deficient mice, a model commonly used for atherosclerosis research. Stress was induced by restraining dams in small cylinders for five consecutive days (2 h/day) beginning on gestational day 8 +/- 0.5. Vascular function and development of atherosclerosis in the aorta were determined in male and female offspring at 11-15 wk of age (with early lesions) and at 22-26 wk of age (with established lesions). Endothelium-dependent vasorelaxation was determined using methacholine (0.0001-10 micromol/l) in the absence or presence of the nitric oxide synthase inhibitor N(omega)-nitro-l-arginine methyl ester hydrochloride (l-NAME; 100 micromol/l). Male offspring (11-15 wk old) from stressed dams were less dependent on nitric oxide for relaxation compared with controls (l-NAME inhibition: 38 +/- 10 vs. 69 +/- 6%, P < 0.05). Atherosclerotic lesion area was larger in male and female 25- to 26-wk-old offspring from stressed dams compared with corresponding controls [median (interquartile range): males: 6.8 (5.4-7.7) vs. 5.1 (4.4-5.5), P < 0.05, females: 10.0 (8.9-10.9) vs. 7.0 (4.7-8.7), P < 0.05]. In conclusion, maternal stress renders the apolipoprotein E-deficient offspring more susceptible to develop atherosclerosis.
Andersson
Irene J
IJ
Depts. of Ob/Gyn, Univ. of Alberta, Edmonton, Canada.
Jiang
Yan-Yan
YY
Davidge
Sandra T
ST
D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology; D001724:Birth Weight; D002784:Cholesterol / Q000097:blood; D003345:Corticosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D008098:Litter Size; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D009929:Organ Size / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology* / Q000523:psychology*; D013315:Stress, Psychological / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology; D014280:Triglycerides / Q000097:blood; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D001057:Apolipoproteins E; D004791:Enzyme Inhibitors; D014280:Triglycerides; D014662:Vasoconstrictor Agents; D009599:Nitroprusside; D010656:Phenylephrine; D009569:Nitric Oxide; D002784:Cholesterol; D052250:Nitric Oxide Synthase Type III; D019331:NG-Nitroarginine Methyl Ester; D003345:Corticosterone