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  • ISSN: 2378-9344
    Volume 7, Issue 1
    Preclinical Research
    Jing Liu, Hisashi Sawada, Deborah A. Howatt, Jessica J. Moorleghen, Olga Vsevolozhskaya, Alan Daugherty, and Hong S. Lu*
    Objective: This study determined whether hypercholesterolemia would contribute to both the initiation and progression of angiotensin (Ang)II-induced abdominal aortic aneurysms (AAAs) in mice.
    Methods and Results: To determine whether hypercholesterolemia accelerates the initiation of AAAs, male low-density lipoprotein (LDL) receptor -/- mice were either fed one week of Western diet prior to starting AngII infusion or initiated Western diet one week after starting AngII infusion. During the first week of AngII infusion, mice fed normal diet had less luminal expansion of the suprarenal aorta compared to those initiated Western diet after the first week of AngII infusion. The two groups achieved comparable luminal dilation on week 2 through week 6 of AngII infusion as monitored by ultrasound. To determine whether hypercholesterolemia contributed to the progression of established AAAs, male LDL receptor -/- mice were fed Western diet and infused with AngII for 4 weeks. Mice with established AAAs were then stratified into two groups based on luminal diameters measured by ultrasound. While AngII infusion was continued for another 8 weeks in both groups, mice in one group were continuously fed Western diet, but diet in the other group was switched to normal laboratory diet. In the latter group, plasma cholesterol concentrations were reduced rapidly to approximately 500 mg/dl within one week after the diet was switched from Western diet to normal laboratory diet. Luminal expansion progressed constantly in mice continuously fed Western diet, whereas no continuous expansion was detected in mice that were switched to normal laboratory diet.
    Conclusion: Hypercholesterolemia accelerates both the initiation of AAAs and progression of established AAAs in AngII-infused male LDL receptor -/- mice.
    Clinical Relevance: Hypercholesterolemia is modestly associated with AAAs in observational or retrospective clinical studies. It is not feasible to study whether hypercholesterolemia contributes to the initiation of AAAs or progression of established AAAs in human. This study using AngII-induced AAA mouse model provides solid evidence that hypercholesterolemia contributes to both the initiation and progression of AAAs, supporting that statin therapy at any stage of AAA development may be beneficial to hypercholesterolemic patients with AAAs.
    Quiz-Answer
    Yash Javeri*, Vitrag Shah and Sanjay Juneja
    Venous thromboembolism (VTE) is a major national health problem, with an overall age- and sex-adjusted incidence of more than ...... per 1,000 annually.
    Research Article
    Nobuo Tomizawa*
    Objectives: To estimate the flow reduction of the aorta when abdominal aortic aneurysm (AAA) is present and to provide an appropriate scan time for CT angiography of the aorta using a small amount of contrast medium when AAA is present.
    Methods: We performed an in vitro study by calculating the aortic flow using commercially available computed fluid dynamics software. We evaluated the following AAA models: aneurysm diameter, 30 to 60 mm; aneurysm length, 30 to 80 mm; inlet flow velocity, 30 to 60 mm/s. We defined ?transit time as the difference in transit time of the aorta with and without AAA.
    Results: Mean aortic flow decreased with increasing aneurysm size and length. The increase in ?transit time was longer in patients with slow aortic flow than fast aortic flow. Quadratic relationship was present between aneurysm diameter and ?transit time and the relationship was very good with R2 values ranging between 0.9972 to 0.9991. The relationship was also good between ?transit time and aneurysm length with R2 values ranging between 0.9986 to 1. ?Transit time was over 2 s especially when the aneurysm length was longer than 70 mm even when the inlet flow velocity was fast.
    Conclusion: Aortic flow would decrease in patients with AAA. The delay in contrast medium arrival increases with aneurysm size and length. Scan time for CT angiography of the aorta should be tailored by AAA size when the contrast medium injection time is short.
    Crystal Yin Tung CHAN, Bernice Lai Yee CHEUK*, and Stephen Wing Keung CHENG
    Objectives: MicroRNA (miR)-1260 was identified to be down-regulated in vascular smooth muscle cells (VSMCs) from human abdominal aortic aneurysm (AAA) tissues in our previous microarray profiling assay. MiR-1260 was predicted to target and down-regulate collagen type 1 alpha 1 (COL1A1), which is closely related to AAA formation, from a bioinformatics analysis. However, the role of miR-1260 in VSMCs for AAA formation still remains uncertain. This study aims to investigate the role of miR-1260 in human VSMCs.
    Methods: Stable overexpression and knockdown of miR-1260 using lentivirus were performed in VSMCs cultured from human abdominal aortic tissues. Expression of COL1A1 protein was investigated, followed by investigating the expressions of several key components involved in AAA pathogenic features: monocyte chemoattractant protein-1 (MCP-1) for inflammation; matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of matrix metalloproteinase (TIMP)-1 and TIMP-2 for elastin fragmentation. Apoptosis of VSMCs was also examined.
    Results: Both COL1A1 and MCP-1 were significantly down-regulated upon miR-1260 overexpression, whereas they were significantly up-regulated upon miR-1260 knockdown. Neither protein expressions of MMP-2, MMP-9, TIMP-1 and TIMP-2 nor apoptosis were significantly different between miR-1260 overexpression/knockdown and corresponding controls.
    Conclusions: Our findings suggested suppression of miR-1260, which was previously found associated with AAA VSMCs, may promote up-regulation of COL1A1 and MCP-1 in human VSMCs, possibly promoting compensatory collagen synthesis and inflammation for AAA formation.
    Review Article
    John Oluwatobiloba Omobowale Ayorinde, Mohamed Morsy, Veena Surendrakumar, Mohammad Ayaz Hossain*
    Patients are living longer than ever on renal replacement therapy, whilst venous access options regularly go down, leaving a growing number of patients without any conventional access routes. This review seeks to summarise and analyse the outcomes associated with ‘last chance’ venous access routes (translumbar, transhepatic, transrenal, sharp recanalisation and limb entry) in order to describe catheter survival, infection rates, and identify specific risks with each of these techniques. We hope this discussion will help clinicians to rationalise the options for patients in this difficult situation.
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