Background-Left ventricular assist device (LVAD) support of the failing heart induces salutary changes in myocardial structure and function. Matrix metalloproteinases (MMPs) are increased in the failing heart and are induced by stretch in cardiac cells in vitro. We hypothesized that mechanical unloading may affect LV plasticity by regulating MMPs and their substrates. Methods and Results-LV samples were collected from patients with dilated cardiomyopathy (DCM, nϭ14) or ischemic cardiomyopathy (ICM, nϭ16) at the time of implantation of the LVAD and again during cardiac transplantation. MMP-1, -3, and -9 were measured by ELISA, MMP-2 and -9 gelatinolytic activity by gelatin zymography, and tissue inhibitors of metalloproteinases (TIMPs) by Western blot. Total soluble and insoluble collagens were separated by pepsin solubilization, and the contents were determined by quantification of hydroxyproline. The undenatured soluble collagen was measured by Sircol collagen assay. The results showed that MMP-1 and -9 were decreased, whereas TIMP-1 and -3 were increased, but there was no change in MMP-2 and -3 and TIMP-2 and -4 after LVAD support. The undenatured collagen was increased, with the ratio of undenatured to total soluble collagens increased in ICM and that of insoluble to total soluble collagens increased in DCM after LVAD support. Conclusions-The reduced MMPs and increased TIMPs and ratios of undenatured to total soluble collagens and insolubleto total soluble collagens after LVAD support suggest that reduced MMP activity diminished damage to the matrix. These changes may contribute to the functional recovery and LV plasticity after LVAD support. Key Words: collagen Ⅲ metalloproteinases Ⅲ remodeling Ⅲ heart-assist device Ⅲ heart failure L eft ventricular assist devices (LVADs) provide mechanical support for the failing heart and serve as a bridge to cardiac transplantation, with the potential to be a destiny therapy for heart failure. [1][2][3] Recent reports demonstrate that LVAD support may be associated with adaptive remodeling of the ventricular myocardium, including reduced LV mass, wall thickness, and myocyte diameter; changes in LV pressure-volume relationships; and reversal of LV chamber dilation and molecular remodeling of proteins involved in Ca 2ϩ cycling. [3][4][5][6][7][8][9][10] In addition, LVAD support has been associated with salutary changes in cardiomyocyte function. Indeed, a small subgroup of patients can be successfully weaned from LVAD after recovery of ventricular function. 6,[11][12][13][14] Although it has been suggested that these beneficial changes are attributed to chronic unloading of the ventricular myocardium, the molecular mechanisms that play a role in LVAD-induced myocardial plasticity and LV remodeling remain undefined. See p 1089We hypothesized that the myocardial remodeling that occurs with LVAD unloading might be attributable to alterations in the components of the extracellular matrix, and specifically in the activity of matrix metalloproteinases (MMPs) and the physical pr...

In this series of patients with new-onset dilated cardiomyopathy treated with high-dose immune globulin, LVEF improved 17 EF units. The effectiveness of intravenous immune globulin therapy in this disorder should be evaluated in a randomized, multicenter trial.

Initiation of pT181 DNA replication specifically requires the plasmid-encoded RepC protein. Here we demonstrate that highly purified RepC protein has sequencespecific endonuclease and topoisomerase-like activities. A maximum sequence of 127 base pairs containing the pT181 origin of replication is required for nicking-closing by RepC protein.RepC introduces a single strand break within the pT181 origin. The nick site has been shown by DNA sequencing to lie between nucleotides 70 and 71 in the bottom strand of the DNA within the origin sequence. This nick site probably corresponds to the start site of pT11 replication. The results presented here suggest that, unlike most other plasmids, pT181 replicates by a rolling circle mechanism.

In this small retrospective study of women with peripartum cardiomyopathy, patients treated with immune globulin had a greater improvement in ejection fraction during early follow-up than patients treated conventionally. Given the poor prognosis of women with peripartum cardiomyopathy who do not improve, this therapy merits further study.