Changes in Inflammatory Response after Endovascular Treatment for Type B Aortic Dissection

This present study aims to investigate the changes in the inflammatory markers after elective endovascular treatment of Type B aortic dissection with aneurysm, as related to different anatomical features of the dissection flap in the paravisceral perfusion. Consecutive patients with type B aortic dissections with elective endovascular stent graft repair were recruited and categorized into different groups. Serial plasma levels of cytokines (Interleukin-1β, -6, -8, -10, TNF-α), chemokines (MCP-1), and serum creatinine were monitored at pre-, peri- and post-operative stages. The length of stent graft employed in each surgery was retrieved and correlated with the change of all studied biochemical parameters. A control group of aortic dissected patients with conventional medication management was recruited for comparing the baseline biochemical parameters. In total, 22 endovascular treated and 16 aortic dissected patients with surveillance were recruited. The endovascular treated patients had comparable baseline levels as the non-surgical patients. There was no immediate or thirty day-mortality, and none of the surgical patients developed post-operative mesenteric ischaemia or clinically significant renal impairment. All surgical patients had detectable pro-inflammatory mediators, but none of the them showed any statistical significant surge in the peri-operative period except IL-1β and IL-6. Similar results were obtained when categorized into different groups. IL-1β and IL-6 showed maximal levels within hours of the endovascular procedure (range, 3.93 to 27.3 higher than baseline; p = 0.001), but returned to baseline 1 day post-operatively. The change of IL-1β and IL-6 at the stent graft deployment was statistically greater in longer stent graft (p>0.05). No significant changes were observed in the serum creatinine levels. In conclusion, elective endovascular repair of type B aortic dissection associated with insignificant changes in inflammatory mediators and creatinine. All levels fell toward basal levels post-operatively suggesting that thoracic endovascular aortic repair is rather less aggressive with insignificant inflammatory modulation

How important are metalloproteinases in aortic dissection?

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Clearance of matrix metalloproteinase-9 is dependent on low-density lipoprotein receptor-related protein-1 expression downregulated by microRNA-205 in human abdominal aortic aneurysm

OBJECTIVE: Low-density lipoprotein receptor-related protein-1 (LRP1) has been suggested to be a crucial regulator in the pathogenesis of abdominal aortic aneurysm (AAA) from previous genome association and animal studies. Our prior study using human aortic samples has further revealed a significant reduction of LRP1 protein expression associated with AAA. However, the downregulation of LRP1 in the pathophysiology of AAA remained unresolved. We hypothesized that LRP1 downregulation may be mediated by microRNA (miR) and that LRP1 may function as a scavenger of matrix metalloproteinase-9 (MMP-9), a well-known protease for degradation of extracellular matrix proteins at the aortic wall for AAA pathogenesis. This study investigated the cause of LRP1 downregulation and its potential effect on AAA pathogenesis. METHODS: An observational study of LRP1 protein, LRP1 messenger RNA (mRNA), and its three predicted miR candidates (miR-205, miR-338-5p, and miR-545-3p) was first performed in AAA compared with nonaneurysmal tissues from humans, followed by a functional study testing the effect on LRP1 expression of miR-205 overexpression and knockdown in human vascular smooth muscle cells (VSMCs) explant cultured from human abdominal aortic tissues. Lastly, another functional study was performed to test for the clearance of exogenous MMP-9 upon silencing of LRP1 in human VSMCs. RESULTS: From the observational study, significantly higher miR-205 (P < .001) and lower LRP1 protein (P < .001) expressions were found in human AAA tissues compared with nonaneurysmal aortic tissues, and no significant difference in LRP1 mRNA expression was observed. Further statistical analysis showed a significant negative correlation between miR-205 and LRP1 protein expressions (r = -0.65; P < .01). For the functional study, a significant downregulation of LRP1 protein expression was shown in miR-205-overexpressing VSMCs (P < .05), without any alteration in LRP1 mRNA expression. Moreover, a significantly reduced clearance of exogenous MMP-9 was observed in LRP1-silenced VSMCs (P < .05), and this difference in MMP-9 clearance was completely abolished with a pretreatment of anti-LRP1 antibody. CONCLUSIONS: Our study revealed the downregulation of LRP1 protein expression may be tightly regulated by miR-205 through translational inhibition in human VSMCs. Also, such LRP1 down-regulation in VSMCs may hinder the removal of pericellular MMP-9, leading to excess MMP-9 remaining in the extracellular matrix. Hence, the integrity of the vascular wall may be disrupted, promoting AAA formation

Tight regulation of low-density lipoprotein receptor-related protein-1 in human aneurysmal aortic tissues

Poster Presentation 1 - 01. Arterial Disease: no. P-00

Alendronate reduced peri-tunnel bone loss and enhanced tendon graft to bone tunnel healing in anterior cruciate ligament reconstruction

Peri-tunnel bone loss after anterior cruciate ligament (ACL) reconstruction is commonly observed, both clinically and experimentally. We aimed to study the effect and mechanisms of different doses of alendronate in the reduction of peri-tunnel bone loss and promotion of graft-bone tunnel healing in ACL reconstruction. Eighty-four ACL-reconstructed rats were divided into 4 groups. Alendronate at different dosages, or saline, were injected subcutaneously weekly, for 2 or 6 weeks post-reconstruction, for vivaCT (computed tomography) imaging, biomechanical tests, histology and immunohistochemistry. Alendronate significantly increased bone mass and density of tissue inside bone tunnels except at the epiphyseal region of tibial tunnel. The femoral tunnel diameter decreased significantly in the mid-dose and high-dose alendronate groups compared to that in the saline group at week 6. Alendronate significantly increased the peri-tunnel bone mass and density along all tunnel regions at week 6. Better graft-bone tunnel integration and intra-tunnel graft integrity were observed in the alendronate groups. The ultimate load was significantly higher in the mid-dose and high-dose alendronate groups at week 2, but not at week 6. There was a reduction in matrix metalloprotein (MMP)1, MMP13 and CD68-positive cells at the peri-tunnel region and graft-bone interface in the alendronate-treated group compared to the saline group. Alendronate reduced peri-tunnel bone resorption, increased mineralised tissue inside bone tunnel as well as histologically and biomechanically promoted graft-bone tunnel healing, probably by reducing the expression of MMP1, MMP13 and CD68-positive cells. Alendronate might be used for reducing peri-tunnel bone loss and promoting graft-bone tunnel healing at early stage post-ACL reconstruction

The roles of bone morphogenetic protein (BMP) 12 in stimulating the proliferation and matrix production of human patellar tendon fibroblasts

Recombinant human (rh) bone morphogenetic protein 12 (BMP12) is proved to induce the formation of tendon and ligament tissues in animal experiments. But the roles of BMP12 on tissue regeneration in human tendons remain unexplored. In the present study, healthy human patellar tendon samples were collected for histological examination and preparation of tendon fibroblast culture. Immunohistochemical staining showed that BMP12 was detected on healthy patellar tendon samples, only located on active tenoblasts and perivascular mesenchymal cells but not in interstitial tenocytes. The expression of PCNA and procollagen type I also exhibited a similar distribution. It indicates that BMP12 may be involved in matrix remodeling process in adult tissues. In vitro studies showed that rhBMP12 could increase proliferation of tendon fibroblasts and increase the gene expression of procollagen type I and type III, but decrease the gene expression of decorin in tendon fibroblasts culture. Our findings suggest that BMP12 may play a role in early phases of tissue regeneration in tendons. © 2003 Published by Elsevier Science Inc.link_to_subscribed_fulltex