title: Cardiac structural and hemodynamic changes associated with physiological heart hypertrophy of pregnancy are reversed postpartum.
abstract: Pregnancy is associated with ventricular hypertrophy and volume overload. Here we investigated whether late pregnancy is associated with cardiac structural and hemodynamic changes, and if these changes are reversed postpartum. Female mice (C57BL/6) were used in nonpregnant diestrus (NP), late-pregnant (LP), or 7-day postpartum (PP7) stages. Echocardiography and cardiac catheterization were performed to monitor cardiac hemodynamics. Transcript expression of proangiogenic vascular endothelial growth factor, cardiac fetal gene osteopontin, cardiac extracellular matrix-degrading enzymes matrix metalloproteinase-2, and a disintegrin and metalloproteinase-15 and -17 were assessed by RT-PCR. Masson trichrome staining for cardiac fibrosis and endothelial marker CD31 immunostaining for angiogenesis were performed. Heart hypertrophy in LP was fully reversed in PP7 (heart weight: NP = 114 ± 4 mg; LP = 147 ± 2 mg; PP7 = 117 ± 8 mg, P < 0.05 for LP vs. PP7). LP had elevated left ventricular (LV) pressure (119 ± 5 mmHg in LP vs. 92 ± 7 mmHg in NP, P < 0.05) that was restored at PP7 (95 ± 8 mmHg, P < 0.001 vs. LP). LP had increased LV contractility (maximal rate of increase of LV pressure = 6,664 ± 297 mmHg/s in LP vs. 4,294 ± 568 mmHg/s in NP, P < 0.01) that was restored at PP7 (5,313 ± 636 mmHg/s, P < 0.05 vs. LP). LV ejection fraction was reduced in LP (LP = 58 ± 1% vs. NP = 70 ± 4%, P < 0.001) and was already restored at PP1 (77 ± 2%, P < 0.001 vs. LP). Myocardial angiogenesis was significantly increased in LP (capillary density = 1.25 ± 0.02 vs. 0.95 ± 0.01 capillaries/myocyte in NP, P < 0.001) and was fully restored in PP7 (0.98 ± 0.01, P < 0.001 vs. LP). Vascular endothelial growth factor was upregulated in LP (LP = 1.4 ± 0.1 vs. NP = 1 ± 0.1, normalized to NP, P < 0.001) and was restored in PP7 (PP7 = 0.83 ± 0.1, P < 0.001 vs. LP). There was no increase in cardiac fibrosis in LP. Matrix metalloproteinase-2 transcript levels were downregulated in LP (LP = 0.47 ± 0.03 vs. NP = 1 ± 0.01, normalized to NP, P < 0.001) and was restored at PP7 (0.70 ± 0.1, P < 0.001 vs. LP). In conclusion, pregnancy-induced heart hypertrophy is associated with transient cardiac dysfunction, increased cardiac angiogenesis, lack of fibrosis, and decreased expression of remodeling enzymes that are reversed postpartum.
authors.affiliation: Department of Anesthesiology, Division of Molecular Medicine David Geffen School of Medicine at University of California-Los Angeles, CA 90095, USA.
authors.forename: Soban
authors.initials: S
authors.lastname: Umar
authors.forename: Rangarajan
authors.initials: R
authors.lastname: Nadadur
authors.forename: Andrea
authors.initials: A
authors.lastname: Iorga
authors.forename: Marjan
authors.initials: M
authors.lastname: Amjedi
authors.forename: Humann
authors.initials: H
authors.lastname: Matori
authors.forename: Mansoureh
authors.initials: M
authors.lastname: Eghbali
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000235:genetics / Q000502:physiology; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D019483:Disintegrins / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D004452:Echocardiography / Q000379:methods; D005260:Female; D005355:Fibrosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D006352:Heart Ventricles / Q000378:metabolism / Q000503:physiopathology*; D006439:Hemodynamics; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D049590:Postpartum Period / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D015854:Up-Regulation / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D019483:Disintegrins; C506896:Spp1 protein, mouse; D042461:Vascular Endothelial Growth Factor A; D053495:Osteopontin; D020782:Matrix Metalloproteinases