Blocking Interleukin-1 Beta Reduces the Evolution of Thoracic Aortic Dissection in a Rodent Model.

OBJECTIVE: Thoracic aortic dissection (TAD) is associated with matrix changes, biochemical changes, and inflammatory markers like interleukin-1 beta (IL-1ß). However, the exact mechanism remains unknown. This study aimed to investigate the role of IL-1ß, matrix metalloproteinase (MMP)-2, MMP-9, smooth muscle cell apoptosis, and elastic fibre fracture in the development of TAD in a rat model. METHODS: The TAD rat model was induced by ß-aminopropionitrile (BAPN). TAD was investigated in 112 male Sprague-Dawley rats, which were equally divided into four groups of 28 rats (Control, BAPN, BAPN + IL-1ß, and BAPN + IL-1ß antibody). Systolic blood pressure, survival, and the development of TAD were measured after six weeks. Expression of IL-1ß, MMP-2, and MMP-9 was measured by Western blot. Apoptosis, aortic elastin concentration, and biomechanical characteristics were measured by the TdT mediated dUTP nick end labelling assay, Victoria blue staining, and in vitro testing. RESULTS: During six weeks, the mortality was 0% (0/28) in the control group, 53.6% (15/28) in the BAPN group (p < .001 compared with the control group), 75.0% (21/28) in the BAPN + IL-1ß group (p = .007 compared with the BAPN group), and 35.7% (10/28) in the BAPN + IL-1ß antibody group (p = .023 compared with BAPN group and p < .001 compared with the BAPN + IL-1ß group). IL-1ß treatment deteriorates BAPN induced mortality and aneurysm expansion, which were attenuated by anti-IL-1ß treatment. In BAPN + IL-1ß group, stress and strain parameters were decreased by 13.5%-53.5% and elastin content was decreased by 14%, and IL-1ß, MMP-2, and MMP-9 were expressed higher by 117%, 108%, and 75% when compared with the rats in the BAPN group. Contrarily, in the BAPN + IL-1ß antibody group, the above changes could be completely (strain, elastin content, and expression of MMP-2) or partly (elasticity modulus, stress, and expression of MMP-9) blocked by anti-IL-1ß treatment. CONCLUSION: IL-1ß plays a critical role in TAD formation by altering the expression of MMP-2 and MMP-9, degrading the aortic wall matrix, causing elastic fibre rupture, and changing the stress or strain of the aortic wall. Anti-IL-1ß reduces the later effects and could be one of the molecular targets for prognosis and drug treatment of TAD in the future.

Which one is the best in treating deep venous thrombosis -- percutaneous mechanical thrombectomy, catheter-directed thrombolysis or combination of them?

OBJECTIVE: To compare the treatment outcomes among percutaneous mechanical thrombectomy (PMT) with AngioJet, Catheter-directed thrombolysis (CDT), and a combination of both. METHODS: One hundred forty nine patients with acute or sub-acute iliac-femoral vein thrombosis accepting CDT and/or PMT were divided into three groups respectively: PMT group, CDT group, PMT + CDT group (PMT followed by CDT). The severity of thrombosis was evaluated by venographic scoring system. Technical success was defined as restored patent deep venous blood flow after CDT and/or PMT. Clinical follow-up were assessed by ultrasound or venography imaging. The primary endpoints were recurrence of DVT, and severity level of post-thrombotic syndrome (PTS) during the follow-up. RESULTS: Technical success and immediate clinical improvements were achieved on all patients. The proportion of sub-acute DVT and the venographic scoring in PMT + CDT group were significantly higher than that in CDT group and PMT group (proportion of sub-acute DVT: p = 0.032 and p = 0.005, respectively; venographic scoring: p < 0.001, respectively). The proportion of May-Thurner Syndrome was lower in PMT group than that in CDT and PMT + CDT group (p = 0.026 and p = 0.005, respectively). The proportion of DVT recurrence/stent thrombosis was significantly higher in CDT group than that in PMT + CDT group (p = 0.04). The severity of PTS was the highest in CDT group ( χ2 = 14.459, p = 0.006) compared to PMT group (p = 0.029) and PMT + CDT group (p = 0.006). CONCLUSION: Patients with sub-acute DVT, high SVS scoring and combined May-Thurner Syndrome were recommended to take PMT + CDT treatment and might have lower rate of DVT recurrence/stent thrombosis and severe PTS. Our study provided evidence detailing of PMT + CDT therapy.

Comparison of ß-aminopropionitrile-induced aortic dissection model in rats by different administration and dosage.

This study compared three ß-aminopropionitrile (BAPN) treatment rats to find the optimal BAPN model for thoracic aortic dissection and aneurysm in one study. Sixty rats were divided into five groups: control, injected control, 0.25% and 0.4% BAPN treatment (orally), and 667 mg/kg/day BAPN injection subcutaneously. Incidence of aortic dissection and aneurysm, aortic weight and diameter were measured directly. Thickness of media and area of aorta were measured by hematoxylin and eosin and Victoria blue staining. The mortality, incidence of aortic dissection and the rupture rate of dissected aneurysm in 0.25% group was much higher than in the other two BAPN treatment groups. The diameter of thoracic aorta in 0.25% and the whole aorta in 0.4% group significantly increased. Media thickness and area of thoracic aorta were increased by 91% and 54% in 0.25% group, and by 17% and 12% in the BAPN injection group. Thickness and area were increased by 49% and 35% on thoracic aorta, and 29% and 46% on abdominal aorta in 0.4% group. In conclusion, 0.25%, 0.4% and BAPN injection groups might be appropriate for aortic dissection and pharmaceutical study, thoracic-abdominal aortic aneurysm or dilation and biomechanical research, respectively.

Glycyrrhizic acid ameliorates the kynurenine pathway in association with its antidepressant effect.

Our previous study implied the role of central high mobility group box 1 (HMGB1) in lipopolysaccharide (LPS)-induced depressive-like behaviors that could partially abrogate by glycyrrhizic acid (GZA). Here, we considered the potential mechanism underlying GZA ameliorating chronic stress-induced depression both in vivo and in vitro. Depression model was established with the 4-week chronic unpredictable mild stress (CUMS) mice. Sucrose preference test, tail suspension test and open field test were performed to reflect depressive-like behaviors. Enzyme activity of indoleamine-2,3-dioxygenase (IDO) was recorded with the ratio of kynurenine (KYN) / tryptophan (Trp). Transcription of gene was evaluated by RT-PCR. Along with depressive-like behaviors, IDO, the rate-limiting enzyme of the kynurenine pathway (KP), was upregulated at the level of mRNA expression, and enzyme activity was also elevated in stressed hippocampi and LPS/HMGB1-treated hippocampus slices. Treatment of mice with GZA, the inhibitor of HMGB1, prevented the activated enzymes in KP and the development of depressive-like behaviors. These experiments demonstrate that GZA may restrain HMGB1 thus improving chronic stress-induced depressive behavior through regulating KP.

[Anti-oxidant effects of Tongxinluo on ATPase in focal brain ischemia-reperfusion rats].

OBJECTIVE: To explore the effects of Tongxinluo on adenosine triphosphatase (ATPase), anti-oxidant enzymes activities, and lipid peroxidation of mitochondria or brain homogenate in focal brain ischemia-reperfusion rats. METHODS: The models of the focal brain ischemia-reperfusion rats were made by the middle cerebral artery occlusion (MCAO). Activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and ATPase and malonaldehyde (MDA) levels of mitochondria or brain homogenate were measured by biochemical methods. RESULTS: Tongxinluo significantly inhibited the decrease of activities of SOD and the increase of MDA levels, but had no difference in GSH-Px in brain homogenate. It also inhibited the decrease of activities of SOD, GSH-Px, ATPase, and the increase of MDA levels in mitochondria. CONCLUSION: The protective mechanisms of Tongxinluo against mitochondrial injuries in focal ischemia-reperfusion rats may be derived from reducing lipid peroxides, scavenging free radicals and improving the energy metabolism.