Reversible physiological cardiac hypertrophy of the maternal heart occurs during pregnancy and involves extracellular matrix (ECM) remodeling. Previous mouse studies revealed that changes in ECM molecules accompany functional changes in the left ventricle (LV) during late pregnancy and postpartum. We evaluated the effect of global Timp4 deletion in female mice on LV functional parameters and ECM molecules during pregnancy and the postpartum period. Heart weights normalized to tibia lengths were increased in Timp4 knockout (Timp4 KO) virgin, pregnant, and postpartum day 2 mice compared with wild types. Serial echocardiography performed on pregnancy days 10, 12, and 18 and postpartum days (ppds) 2, 7, 14, 21, and 28 revealed that both wild-type and Timp4 KO mice increased end systolic and end diastolic volumes (ESV, EDV) by mid to late pregnancy compared with virgins, with EDV changes persisting through the postpartum period. When compared with wild types, Timp4 KO mice exhibited higher ejection fractions in virgins, at pregnancy days 10 and 18 and ppd2 and ppd14. High-molecular weight forms of COL1A1 and COL3A1 proteins in LV were greater in Timp4 KO virgins, and COL1A1 was higher in late pregnancy and on ppd2 compared with wild types. With exceptions, Timp4 KO mice during late pregnancy and the early postpartum period were able to maintain stroke volume similar to wild-type mice through increased ejection fraction. Although TIMP4 deletion in females exhibited altered ECM molecules, it did not adversely affect cardiac function during first pregnancies and lactation.

NEW & NOTEWORTHY Pregnancy and lactation increase volume load on the heart. Defects in cardiac remodeling during pregnancy and postpartum can result in peripartum cardiomyopathy. TIMPs participate in cardiac remodeling. The present study reports the cardiac function in Timp4 knockout adult female mice during pregnancy and lactation. Timp4 knockout females at many time points have higher ejection fraction to maintain stroke volume. Global deletion of Timp4 was not detrimental to maternal heart function during first pregnancies and lactation.