title: Pregnancy mitigates cardiac pathology in a mouse model of left ventricular pressure overload.
abstract: In Western countries heart disease is the leading cause of maternal death during pregnancy. The effect of pregnancy on the heart is difficult to study in patients with preexisting heart disease. Since experimental studies are scarce, we investigated the effect of pressure overload, produced by transverse aortic constriction (TAC) in mice, on the ability to conceive, pregnancy outcome, and maternal cardiac structure and function. Four weeks of TAC produced left ventricular (LV) hypertrophy and dysfunction with marked interstitial fibrosis, decreased capillary density, and induced pathological cardiac gene expression. Pregnancy increased relative LV and right ventricular weight without affecting the deterioration of LV function following TAC. Surprisingly, the TAC-induced increase in relative heart and lung weight was mitigated by pregnancy, which was accompanied by a trend towards normalization of capillary density and natriuretic peptide type A expression. Additionally, the combination of pregnancy and TAC increased the cardiac phosphorylation of c-Jun, and STAT1, but reduced phosphoinositide 3-kinase phosphorylation. Finally, TAC did not significantly affect conception rate, pregnancy duration, uterus size, litter size, and pup weight. In conclusion, we found that, rather than exacerbating the changes associated with cardiac pressure overload, pregnancy actually attenuated pathological LV remodeling and mitigated pulmonary congestion, and pathological gene expression produced by TAC, suggesting a positive effect of pregnancy on the pressure-overloaded heart.
authors.affiliation: Department of Cardiology, Thoraxcenter, Erasmus MC, University Medical Center Rotterdam, The Netherlands; Department of Cardiac Surgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, Peoples Republic of China;
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Thoraxcenter, Erasmus MC, University Medical Center Rotterdam, The Netherlands;
authors.forename: Elza D
authors.initials: ED
authors.lastname: van Deel
authors.affiliation: Academic Department of Obstetrics and Gynaecology, Imperial College London, Chelsea and Westminster Hospital, United Kingdom; and.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Johnson
authors.affiliation: Department of Cardiology, Thoraxcenter, Erasmus MC, University Medical Center Rotterdam, The Netherlands;
authors.forename: Petra
authors.initials: P
authors.lastname: Opić
authors.affiliation: Academic Department of Obstetrics and Gynaecology, Imperial College London, Chelsea and Westminster Hospital, United Kingdom; and.
authors.forename: Bronwen R
authors.initials: BR
authors.lastname: Herbert
authors.affiliation: Department of Cardiology, Thoraxcenter, Erasmus MC, University Medical Center Rotterdam, The Netherlands; Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
authors.forename: Els
authors.initials: E
authors.lastname: Moltzer
authors.affiliation: Academic Department of Obstetrics and Gynaecology, Imperial College London, Chelsea and Westminster Hospital, United Kingdom; and.
authors.forename: Suren R
authors.initials: SR
authors.lastname: Sooranna
authors.affiliation: Department of Cardiology, Thoraxcenter, Erasmus MC, University Medical Center Rotterdam, The Netherlands;
authors.forename: Heleen
authors.initials: H
authors.lastname: van Beusekom
authors.affiliation: Department of Cardiac Surgery, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, Peoples Republic of China;
authors.forename: Wang-Fu
authors.initials: WF
authors.lastname: Zang
authors.affiliation: Department of Cardiology, Thoraxcenter, Erasmus MC, University Medical Center Rotterdam, The Netherlands;
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Duncker
authors.affiliation: Department of Cardiology, Thoraxcenter, Erasmus MC, University Medical Center Rotterdam, The Netherlands; j.roos@erasmusmc.nl.
authors.forename: Jolien W
authors.initials: JW
authors.lastname: Roos-Hesselink
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001024:Aortic Valve Stenosis / Q000150:complications / Q000503:physiopathology*; D009320:Atrial Natriuretic Factor / Q000235:genetics; D001724:Birth Weight; D002196:Capillaries / Q000473:pathology; D004195:Disease Models, Animal; D004452:Echocardiography; D005260:Female; D005355:Fibrosis; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D008098:Litter Size; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000473:pathology; D018995:Myosin Heavy Chains / Q000235:genetics; D020097:Natriuretic Peptide, Brain / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D018873:Pregnancy Rate; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics; D013997:Time Factors; D059467:Transcriptome; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*
chemical_list: C584019:Myh6 protein, mouse; C551613:Myh7 protein, mouse; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D019869:Phosphatidylinositol 3-Kinases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D018995:Myosin Heavy Chains; C506947:Atp2a2 protein, mouse
keywords: aorta stenosis; cardiac dysfunction; cardiac remodeling; fertility; pregnancy