ADAMTS2 (A Disintegrin and Metalloproteinase With Thrombospondin Motifs 2) is recognized as a metalloproteinase that promotes the cleavage of amino propeptides of types I, II, III, and V procollagens. However, the role of ADAMTS2 in the heart has not yet been defined. Herein, we observed the upregulated expression of ADAMTS2 in failing human hearts and hypertrophic murine hearts. Mice lacking ADAMTS2 display exacerbated cardiac hypertrophy on pressure overload-induced hypertrophic response, whereas mice with cardiac-specific overexpression of ADAMTS2 display alleviation of this detrimental phenotype. Consistent with these results, in vitro loss or gain of function experiments in neonatal rat cardiomyocytes confirmed that ADAMTS2 negatively regulates cardiomyocyte hypertrophy in response to Ang II. Mechanistically, blockage of the PI3K (phosphoinositide 3-kinase)/AKT (protein kinase B)-dependent signaling pathway with specific inhibitors both in vivo and in vitro could rescue the aggravated hypertrophic response to the loss of ADAMTS2. Collectively, we propose that ADAMTS2 regulates the hypertrophic response through inhibiting the activation of the PI3K/AKT-dependent signaling pathway. Because ADAMTS2 is an extracellular protein, it could be effectively manipulated using pharmacological means to modulate cardiac hypertrophy.
The stented elephant trunk technique in aortic arch replacement combined with transaortic stented graft implantation into the descending aorta has been introduced as a means of eliminating the residual false lumen in the descending thoracic aorta and improving long-term outcomes of surgical intervention for Debakey I aortic dissection. This report summarizes the operative and follow-up data with this new procedure. Between August 2004 and May 2009, 28 stented elephant trunk operations were performed for Debakey I aortic dissection at Nanjing First Hospital. A 10 cm long woven Dacron graft was implanted through the aortic arch during hypothermic circulatory arrest. Patent false lumina were evaluated using computed tomography three months after the operation. Mean cardiopulmonary bypass time was 213.2±47.2 min, and selected cerebral perfusion time was 38.8±9.7 min. Hospital mortality was 14.3% (4/28). Thrombus obliteration of the residual false lumen in the descending aorta was observed in 91.7% of the aortic dissections three months postoperatively. The survival rate was 87.5% at five years and the freedom from reoperation rate was 91.7%. Total aortic arch replacement combined with transaortic stented graft implantation into the descending aorta is an effective treatment for Debakey type I aortic dissection.
Pericardial fluid (PF) is considered as a biochemical window of heart. To date, there have been limited attempts to perform an in-depth analysis of the PF proteome. In this study, an SDS-PAGE-LC-MS/MS platform was utilized to explore depleted PF, which showed great coverage of low-abundant proteins. In total, 1007 nonredundant proteins were identified with at least two peptides. This is the first comprehensive analysis of human PF proteome and provides a foundation for further application of PF in cardiovascular research. The data have been deposited to the ProteomeXchange with identifier PXD000194.
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