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Pregnancy-Associated Cardiac Hypertrophy in Corin-Deficient Mice: Observations in a Transgenic Model of Preeclampsia

Rachael C. Baird, Shuo Li, Hao Wang, Sathyamangla V. Naga Prasad, David Majdalany, Uma Perni, Qingyu Wu
Canadian Journal of Cardiology2019
Background: Preeclampsia increases the risk of heart disease. Defects in the protease corin, including the variant T555I/Q568P found in approximately 12% of blacks, have been associated with preeclampsia and cardiac hypertrophy. The objective of this study was to investigate the role of corin and the T555I/Q568P variant in preeclampsia-associated cardiac alterations using genetically modified mouse models. Methods: Virgin wild-type (WT) and corin knockout mice with or without a cardiac WT corin or T555I/Q568P variant transgene were mated at 3 or 6 months of age. Age- and genotype-matched virgin mice were used as controls. Cardiac morphology and function were assessed at gestational day 18.5 or 28 days postpartum by histologic and echocardiographic analyses. Results: Pregnant corin knockout mice at gestational day 18.5 developed cardiac hypertrophy. Such a pregnancy-associated phenotype was not found in WT or corin knockout mice with a cardiac WT corin transgene. Pregnant corin knockout mice with a cardiac T555I/Q568P variant transgene developed cardiac hypertrophy similar to that in pregnant corin knockout mice. The cardiac hypertrophy persisted postpartum in corin knockout mice and was worse if the mice were mated at 6 instead of 3 months of age. There was no hypertrophy-associated decrease in cardiac function in pregnant corin knockout mice. Conclusions: In mice, corin deficiency causes cardiac hypertrophy during pregnancy. Replacement of cardiac WT corin, but not the T555I/Q568P variant found in blacks, rescues this phenotype, indicating a local antihypertrophic function of corin in the heart. Corin deficiency may represent an underlying mechanism in preeclampsia-associated cardiomyopathies.
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