Circulation
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An estimated 275,000 patients undergo heart valve replacement each year. However, existing solutions for valve replacement are complicated by the morbidity associated with lifelong anticoagulation of mechanical valves and the limited durability of bioprostheses. Recent advances in tissue engineering and our understanding of stem cell biology may provide a lifelong solution to these problems. ⋯ Stem-cell tissue-engineered heart valves can be created from mesenchymal stem cells in combination with a biodegradable scaffold and function satisfactorily in vivo for periods of >4 months. Furthermore, such valves undergo extensive remodeling in vivo to resemble native heart valves.
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We previously reported that bone morphogenetic protein 2 (BMP2) protected against apoptosis of serum-deprived cardiomyocytes via induction of Bcl-xL through the Smad1 pathway. To investigate whether Smad1 signaling promotes cell survival in the adult heart, we subjected transgenic mice with cardiac-specific overexpression of smad1 gene (Smad1TG) to ischemia-reperfusion (I/R) injury. ⋯ These findings suggest that the Smad1 signaling pathway plays a role in cardioprotection against I/R injury.
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Comparative Study
Serotonin transporter inhibition prevents and reverses monocrotaline-induced pulmonary hypertension in rats.
Progression of pulmonary hypertension (PH) is associated with increased lung expression of the serotonin transporter (5-HTT), which leads to hyperplasia of the pulmonary artery smooth muscle cells (PA-SMCs). Given the postulated causal relation between 5-HTT overexpression and PH, we herein investigated whether the highly selective 5-HTT inhibitor fluoxetine prevented and/or reversed PH induced by monocrotaline (MCT) in rats. Selective 5-HT(1B/1D), 5-HT(2A), and 5-HT(2B) receptor antagonists were used for comparative testing. ⋯ Upregulation of lung 5-HTT induced by MCT appears necessary to initiate the development of pulmonary vascular remodeling, whereas a sustained increase in 5-HTT expression may underlie both the progression and the maintenance of MCT-induced PH. Complete reversal of established PH by fluoxetine provides a rationale for new therapeutic strategies in human PH.
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One of the most hotly debated and polarizing issues in cardiac surgery has been whether coronary artery bypass grafting (CABG) without the use of cardiopulmonary bypass or cardioplegia (off-pump CABG, or OPCAB) is superior to that performed with the heart-lung machine and the heart's being chemically arrested (standard CABG). Various clinical trials are reviewed comparing the 2 surgical strategies, including several large retrospective analyses, meta-analyses, and the randomized trials that address different aspects of standard CABG and OPCAB. Although definitive conclusions about the relative merits of standard CABG and OPCAB are difficult to reach from these varied randomized and nonrandomized studies, several generalizations may be possible. ⋯ Fewer grafts tend to be performed with OPCAB than with standard CABG. Length of hospital stay, mortality rate, and long-term neurological function and cardiac outcome appear to be similar in the 2 groups. To definitively answer the remaining questions of whether either strategy is superior and in which patients, a large-scale prospective randomized trial is required.
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Previous studies suggest that erythrocyte membranes from intraplaque hemorrhage into the necrotic core are a source of free cholesterol and may become a driving force in the progression of atherosclerosis. We have shown that MRI can accurately identify carotid intraplaque hemorrhage and precisely measure plaque volume. We tested the hypothesis that hemorrhage into carotid atheroma stimulates plaque progression. ⋯ Hemorrhage into the carotid atherosclerotic plaque accelerated plaque progression in an 18-month period. Repeated bleeding into the plaque may produce a stimulus for the progression of atherosclerosis by increasing lipid core and plaque volume and creating new destabilizing factors.