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1.
Ann Thorac Surg ; 95(2): 570-7, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23245439

ABSTRACT

BACKGROUND: ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) is a recently identified family of extracellular metalloproteinases that has been shown to participate in tissue destruction. We hypothesized that ADAMTS-1 and ADAMTS-4 expression is increased in aortic tissues from patients with thoracic aortic aneurysms and dissections. METHODS: We examined ADAMTS-1 and ADAMTS-4 expression in human descending thoracic aortic aneurysms (n = 14), chronic descending thoracic aortic dissections (n = 16), and descending thoracic aortas from age-matched control organ donors (n = 12). In these tissues, we also evaluated the degradation of versican, a proteoglycan substrate of ADAMTS-1 and ADAMTS-4. In cultured macrophages, we examined whether ADAMTS-4 functions in macrophage infiltration by using a transwell assay. RESULTS: ADAMTS-1 and ADAMTS-4 protein and mRNA expression was significantly higher in thoracic aortic aneurysm and dissection tissues than in control aortic tissues. Double immunofluorescence staining showed the expression of ADAMTS-1 and ADAMTS-4 in smooth muscle cells and macrophages. Consistent with the upregulation of ADAMTS-1 and ADAMTS-4 in thoracic aortic aneurysm and dissection tissues, versican was degraded significantly more in these tissues than in control aortic tissues. In cultured macrophages, transforming growth factor-ß increased ADAMTS-4 protein levels and induced macrophage invasion, and the knockdown of ADAMTS-4 reduced cell invasion. CONCLUSIONS: Increased expression of ADAMTS proteins may promote thoracic aortic aneurysm progression by degrading versican and facilitating macrophage invasion.


Subject(s)
ADAM Proteins/blood , Aortic Aneurysm, Thoracic/blood , Aortic Dissection/blood , Procollagen N-Endopeptidase/blood , ADAMTS1 Protein , ADAMTS4 Protein , Female , Humans , Male , Middle Aged
3.
J Thorac Cardiovasc Surg ; 137(5): 1124-32, 2009 May.
Article in English | MEDLINE | ID: mdl-19379977

ABSTRACT

OBJECTIVE: A prospective, international registry study was initiated to provide contemporary comparative data on short-term clinical outcomes after aortic valve-sparing and aortic valve-replacing root operations in patients with Marfan syndrome. The purpose of this initial report is to describe the study design and to compare early outcomes in the first 151 enrolled patients. METHODS: We assessed 30-day outcomes in 151 patients who met strict Ghent diagnostic criteria for Marfan syndrome and underwent aortic root replacement with either valve-replacing (n = 46) or valve-sparing techniques (n = 105) at one of 18 participating centers. In the valve replacement group, a mechanical composite valve graft was used in 39 (85%) patients and a bioprosthetic valve in 7 (15%). In the valve-sparing group, David V procedures were performed in 57 (54%) patients, David I in 38 (36%), David IV in 8 (8%), Florida sleeve in 1 (1%), and Yacoub remodeling in 1 (1%). RESULTS: No in-hospital or 30-day deaths occurred. Despite longer crossclamp and cardiopulmonary bypass times in the valve-sparing group, there were no significant between-group differences in postoperative complications. Thirty-day valve-related complications occurred in 2 (4%) patients undergoing valve replacement and in 3 (3%) undergoing valve-sparing procedures (P = .6). CONCLUSIONS: The analysis of early outcomes revealed that valve-sparing techniques were the most common approach to root replacement in patients with Marfan syndrome in these centers. The complexity of valve-sparing root replacement did not translate into any demonstrable adverse early outcomes. Subsequent analysis will compare the 3-year durability of these two surgical approaches.


Subject(s)
Aortic Valve/surgery , Heart Valve Diseases/surgery , Heart Valve Prosthesis Implantation/methods , Hospital Mortality/trends , Marfan Syndrome/complications , Adolescent , Adult , Aged , Aorta, Thoracic/physiopathology , Aorta, Thoracic/surgery , Aortic Valve/physiopathology , Bioprosthesis , Cardiac Surgical Procedures/methods , Cardiopulmonary Bypass/methods , Child , Child, Preschool , Female , Follow-Up Studies , Heart Valve Diseases/etiology , Heart Valve Diseases/mortality , Heart Valve Prosthesis , Heart Valve Prosthesis Implantation/mortality , Humans , Male , Marfan Syndrome/surgery , Middle Aged , Postoperative Complications/mortality , Postoperative Complications/physiopathology , Probability , Prospective Studies , Prosthesis Failure , Registries , Risk Assessment , Survival Analysis , Time Factors , Treatment Outcome , Young Adult
4.
J Thorac Cardiovasc Surg ; 137(3): 641-9, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19258081

ABSTRACT

OBJECTIVE: A prospective, international registry study was initiated to provide contemporary comparative data on short-term clinical outcomes after aortic valve-sparing and aortic valve-replacing root operations in patients with Marfan syndrome. The purpose of this initial report is to describe the study design and to compare early outcomes in the first 151 enrolled patients. METHODS: We assessed 30-day outcomes in 151 patients who met strict Ghent diagnostic criteria for Marfan syndrome and underwent aortic root replacement with either valve-replacing (n = 46) or valve-sparing techniques (n = 105) at one of 18 participating centers. In the valve replacement group, a mechanical composite valve graft was used in 39 (85%) patients and a bioprosthetic valve in 7 (15%). In the valve-sparing group, David V procedures were performed in 57 (54%) patients, David I in 38 (36%), David IV in 8 (8%), Florida sleeve in 1 (1%), and Yacoub remodeling in 1 (1%). RESULTS: No in-hospital or 30-day deaths occurred. Despite longer crossclamp and cardiopulmonary bypass times in the valve-sparing group, there were no significant between-group differences in postoperative complications. Thirty-day valve-related complications occurred in 2 (4%) patients undergoing valve replacement and in 3 (3%) undergoing valve-sparing procedures (P = .6). CONCLUSIONS: The analysis of early outcomes revealed that valve-sparing techniques were the most common approach to root replacement in patients with Marfan syndrome in these centers. The complexity of valve-sparing root replacement did not translate into any demonstrable adverse early outcomes. Subsequent analysis will compare the 3-year durability of these two surgical approaches.


Subject(s)
Aortic Valve/surgery , Heart Valve Prosthesis , Marfan Syndrome/surgery , Adolescent , Adult , Aged , Cardiac Surgical Procedures/methods , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Prospective Studies , Registries , Time Factors , Treatment Outcome
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