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An Unkind Cut Can Lead to a Broken Heart

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Science  23 Feb 2007:
Vol. 315, Issue 5815, pp. 1055
DOI: 10.1126/science.315.5815.1055c

Postpartum (or peripartum) cardiomyopathy (PPCM), which occurs up to a few months after delivery (or late in pregnancy), is associated with an acute onset of heart failure in women with no history of heart disease. Hilfiker-Kleiner et al. have linked cardiomyocyte STAT3 (signal transducer and activator of transcription 3) to PPCM. Normally, pregnancy is associated with cardiac hypertrophy and increased capillary density—physiological changes that also were found to occur in mice lacking cardiac STAT3. However, postpartum mice lacking cardiac STAT3 lost the increased capillary density. These mice suffered an attenuated increase in cardiac manganese superoxide dismutase, which led to excessive levels of reactive oxygen species, which led, in turn, to an increased abundance of the proteolytic enzyme cathepsin D. Furthermore, the STAT3-deficient mice exhibited enhanced cleavage of full-length prolactin, which is a cathepsin D substrate, into a shorter, antiangiogenic form. Increasing the amount of circulating prolactin stimulated cardiac damage in mice that overexpressed cardiac cathepsin D. In contrast, pharmacological inhibition of prolactin secretion prevented PPCM. A preliminary study suggested that inhibiting prolactin release by administering bromocriptine was protective of cardiac function in women at high risk of PPCM. Thus, the authors suggest that cardiac STAT3 is critical to postpartum cardiac function and propose that inhibiting prolactin release may be a viable approach to PPCM treatment. — EMA

Cell 128, 589 (2007).

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