Loss of TIMP4 (Tissue Inhibitor of Metalloproteinase 4) Promotes Atherosclerotic Plaque Deposition in the Abdominal Aorta Despite Suppressed Plasma Cholesterol Levels.

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ADAM (a Disintegrin and Metalloproteinase) 15 Deficiency Exacerbates Ang II (Angiotensin II)-Induced Aortic Remodeling Leading to Abdominal Aortic Aneurysm.

OBJECTIVE: ADAM (a disintegrin and metalloproteinase) 15-a membrane-bound metalloprotease from the ADAM (disintegrin and metalloproteinase) family-has been linked to endothelial permeability, inflammation, and metastasis. However, its function in aortic aneurysm has not been explored. We aimed to determine the function of ADAM15 in the pathogenesis of aortic remodeling and aneurysm formation. Approach and Results: Male Adam15-deficient and WT (wild type) mice (10 weeks old), on standard laboratory diet, received Ang II (angiotensin II; 1.5 mg/kg per day) or saline (Alzet pump) for 2 or 4 weeks. Ang II increased ADAM15 in WT aorta, while Adam15-deficiency resulted in abdominal aortic aneurysm characterized by loss of medial smooth muscle cells (SMCs), elastin fragmentation, inflammation, but unaltered Ang II-mediated hypertension. In the abdominal aortic tissue and primary aortic SMCs culture, Adam15 deficiency decreased SMC proliferation, increased apoptosis, and reduced contractile properties along with F-actin depolymerization to G-actin. Ang II triggered a markedly greater increase in THBS (thrombospondin) 1 in Adam15-deficient aorta, primarily the medial layer in vivo, and in aortic SMC in vitro; increased SSH1 (slingshot homolog 1) phosphatase activity and cofilin dephosphorylation that promoted F-actin depolymerization and G-actin accumulation. rhTHBS1 (recombinant THBS1) alone was sufficient to activate the cofilin pathway, increase G-actin, and induce apoptosis of aortic SMCs, confirming the key role of THBS1 in this process. Further, in human abdominal aortic aneurysm specimens, decreased ADAM15 was associated with increased THBS1 levels and loss of medial SMCs. CONCLUSIONS: This study is the first to demonstrate a key role for ADAM15 in abdominal aortic aneurysm through regulating the SMC function, thereby placing ADAM15 in a critical position as a potential therapeutic target for abdominal aortic aneurysm.

99mTc-WBC scintigraphy with SPECT/CT in the evaluation of arterial graft infection.

OBJECTIVE: The goals of our study were to retrospectively review our experience in using Tc-white blood cell (WBC) single-photon emission computed tomography/computed tomography (SPECT/CT) imaging in the evaluation of possible arterial graft infection and to attempt to establish objective criteria for assessment. METHODS: Eleven Tc-WBC SPECT/CT studies performed for the evaluation of clinically suspected arterial graft infection were retrospectively reviewed and compared with reference outcomes. In an attempt to define objective criteria for interpretation, comparison was also made with background liver and bone marrow activity. RESULTS: When compared with reference outcomes, the subjective scan interpretations showed 6 of 11 true positives (TP), 4 of 11 true negatives (TN), and 1 of 11 false positive (FP). Using the liver as a comparator resulted in 4 of 10 TP, 5 of 10 TN, and 1 of 10 FN. Using the bone marrow as a comparator resulted in 3 of 10 TP, 5 of 10 TN, and 2 of 10 FN. In one patient neither the liver nor the bone marrow was in the field of view. CONCLUSION: These findings suggest a high accuracy for Tc-WBC SPECT/CT in assessing clinically suspected arterial graft infection. Furthermore, the liver may be the best objective comparator for standardized interpretation.

Endovascular repair in traumatic thoracic aortic injuries: comparison with open surgical repair.

PURPOSE: Thoracic endovascular aortic repair (TEVAR) has emerged as an alternative to open surgical repair (OSR) of traumatic thoracic aortic injury (TTAI). Herein immediate and midterm outcomes of TEVAR are compared with those of OSR. MATERIALS AND METHODS: Health records were used to identify patients with TTAI presenting between April 1995 and September 2006. Preoperative patient characteristics, intraoperative variables, procedural costs, and outcomes were recorded. RESULTS: A total of 103 patients were identified. Twenty-two died before treatment, 19 were treated conservatively, 36 received OSR, and 26 received TEVAR. In the OSR group, time from diagnosis to treatment was 8 hours, the 30-day mortality rate was 11.1%, and all deaths occurred intraoperatively. Thoracic nerve injury occurred in four patients (12.5%), pneumonia in 12 (37.5%), temporary renal failure in one (3%), paraparesis in three (9.4%), and paraplegia in five (15.6%). On follow-up (mean, 61 months), postthoracotomy pleural reaction was seen in three cases (9.4%). In the TEVAR group, time to treatment was 38 hours (P < .01) and the 30-day mortality rate was 7.4% with no intraoperative deaths. Pneumonia was seen in two cases (8.3%) and left arm ischemia was seen in two of 17 patients in whom the left subclavian artery was covered. On midterm follow-up (mean, 17 months), there were no graft failures or repeat aortic interventions. Costs of each procedure were initially comparable, but follow-up expenses with TEVAR were $1,284 (Canadian) greater per year. CONCLUSIONS: TEVAR of TTAI is associated with lower perioperative mortality and morbidity rates than OSR, with no significant graft-related complications on midterm follow-up. The study data support the continued use of TEVAR in this context.