Gestational hypertension and the developmental origins of cardiac hypertrophy and diastolic dysfunction.
The developmental origins of health and disease refer to the theory that adverse maternal environments influence fetal development and the risk of cardiovascular disease in adulthood. We used the chronically hypertensive atrial natriuretic peptide knockout (ANP-/-) mouse as a model of gestational hypertension, and attempted to determine the effect of gestational hypertension on left ventricular (LV) structure and function in adult offspring. We crossed normotensive ANP+/+ females with ANP-/- males (yielding ANP+/-(WT) offspring) and hypertensive ANP-/- females with ANP+/+ males (yielding ANP+/-(KO) offspring). Cardiac gene expression was measured using real-time quantitative PCR. Cardiac function was assessed using echocardiography. Daily injections of isoproterenol (ISO) were used to induce cardiac stress. Collagen deposition was assessed using picrosirius red staining. All mice were 10 weeks of age. Gestational hypertension resulted in significant LV hypertrophy in offspring, with no change in LV function. Treatment with ISO resulted in significant LV diastolic dysfunction with a restrictive filling pattern (increased E/A ratio and E/e') and interstitial myocardial fibrosis only in ANP+/-(KO) and not ANP+/-(WT) offspring. Gestational hypertension programs adverse LV structural and functional remodeling in offspring. These data suggest that adverse maternal environments may increase the risk of heart failure in offspring later in life.
Department of Biomedical and Molecular Sciences, Queen's University, Room 850 Botterell Hall, Kingston, ON, K7L 3N6, Canada.
David W J
DW
Armstrong
M Yat
MY
Tse
Philip G
PG
Wong
Nicole M
NM
Ventura
Jalna A
JA
Meens
Amer M
AM
Johri
Murray F
MF
Matangi
Stephen C
SC
Pang
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D006332:Cardiomegaly / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D005355:Fibrosis; D050980:GATA Transcription Factors / Q000378:metabolism; D046110:Hypertension, Pregnancy-Induced / Q000473:pathology* / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D018345:Mice, Knockout; D008955:Models, Cardiovascular; D009206:Myocardium / Q000473:pathology; D011247:Pregnancy; D014463:Ultrasonography; D018487:Ventricular Dysfunction, Left / Q000150:complications* / Q000000981:diagnostic imaging / Q000503:physiopathology*
D000318:Adrenergic beta-Agonists; D050980:GATA Transcription Factors; D009320:Atrial Natriuretic Factor; D007545:Isoproterenol