Hyung Sub Park

Potential role of vascular smooth muscle cell-like progenitor cell therapy in the suppression of experimental abdominal aortic aneurysms

Abdominal aortic aneurysms (AAA) are a growing problem worldwide, yet there is no known medical therapy. The pathogenesis involves degradation of the elastic lamina by two combined mechanisms: increased degradation of elastin by matrix metalloproteinases (MMP) and decreased formation of elastin due to apoptosis of vascular smooth muscle cells (VSMC). In this study, we set out to examine the potential role of stem cells in the attenuation of AAA formation by inhibition of these pathogenetic mechanisms. Muscle-derived stem cells from murine skeletal muscles were isolated and stimulated with PDGF-BB in vitro for differentiation to VSMC-like progenitor cells (VSMC-PC). These cells were implanted in to elastase-induced AAAs in rats. The cell therapy group had decreased rate of aneurysm formation compared to control, and MMP expression at the genetic, protein and enzymatic level were also significantly decreased. Furthermore, direct implantation of VSMC-PCs in the intima of harvested aortas was visualized under immunofluorescent staining, suggesting that these cells were responsible for the inhibition of MMPs and consequent attenuation of AAA formation. These results show a promising role of stem cell therapy for the treatment of AAAs, and with further studies, may be able to reach clinical significance.

Midterm Results of Radiofrequency Ablation for Incompetent Small Saphenous Vein in Terms of Recanalization and Sural Neuritis

BACKGROUND Safety and effectiveness of radiofrequency ablation for incompetent small saphenous vein is not established. OBJECTIVE To report midterm clinical and ultrasonograhic results of radiofrequency ablation (RFA) for small saphenous vein (SSV) in terms of recanalization and sural neuritis. METHODS AND MATERIALS We examined 39 patients (46 limbs) who had been examined using a duplex scan more than 1 year after RFA of SSV. Postoperative clinical results, risk factors for SSV recanalization, and sural neuritis were analyzed. RESULTS CEAP score and CIVIQ2 score improved significantly in all patients (CEAP: 2.45 to 1.43 (p = .03); CIVIQ2: 25.34 to 13.21 (p = .01). SSV obliteration rate was 93.4% at 1 year and 89.1% at 2 years. Preoperative peak reflux velocity in the recanalization group (54.9 cm/s) was significantly higher (p < .01) than in the obliteration group (29.8 cm/s). Sural neuritis were detected in 12 limbs (26.1%), and median symptom duration was 3 months. The total length of RFA ablation was not different between the groups with and without postablation sural neuritis. CONCLUSION RFA is an effective and safe treatment modality for incompetent SSV. Peak reflux velocity can be a risk factor for recanalization. Length of RFA segment in SSV does not affect recanalization and postablation sural neuritis.

Muscle-Derived Stem Cells Promote Angiogenesis and Attenuate Intimal Hyperplasia in Different Murine Vascular Disease Models

Muscle-derived stem cells (MDSCs) are known to promote angiogenesis, but have never been studied in vascular diseases. We differentiated MDSCs into endothelial lineage cells in vitro by stimulation with shear stress and vascular endothelial growth factor. Such differentiated MDSCs (diff-MDSC) showed strong angiogenic potential in vitro. When tested in ischemic hindlimbs of mice, diff-MDSCs increased perfusion and decreased necrosis of the ischemic limbs, by promoting new vessel formation and by upregulating genes involved in endothelial expression. Such effects were not observed with native MDSCs (without endothelial stimulation in vitro). Diff-MDSCs were also injected into carotid arteries of rats after balloon denudation of the intima layer to induce intimal hyperplasia. The cell-treated group had significantly reduced intima-to-media thickness ratio compared to control, thus attenuating intimal hyperplasia by early re-endothelialization of the intima layer. Our findings suggest that MDSCs are a potential source of stem cell therapy for treatment of various vascular diseases, by inducing angiogenesis to improve perfusion in sites of ischemia, and by preventing intimal hyperplasia in sites of vessel injury.

Prospective nonrandomized comparison of quality of life and recurrence between high ligation and stripping and radiofrequency ablation for varicose veins

Purpose Varicose veins are a major problem worldwide and improvement in quality of life (QoL) is the ultimate goal after treatment of this benign disease. However QoL is highly dependent on personal and social factors. This study compares high ligation and stripping (HS) and radiofrequency ablation (RFA) in terms of QoL and recurrence in Korea. Methods A retrospective analysis of prospectively collected data between August 2006 and October 2008 was performed for patients undergoing HS and RFA at a single institution. QoL was assessed with a questionnaire preoperatively, at 3 months postoperatively and annually thereafter. Recurrence was assessed by Duplex ultrasound annually after surgery. RESULTS A total of 272 patients completed the questionnaire at 3 months. Among these patients, 155 patients returned for their annual follow-up. There were no significant differences between HS and RFA in global QoL scores, although RFA showed less pain. However, paresthesia rates were also higher after RFA. Recurrence rates were similar between the two modalities, although technical failures were more common after RFA. Conclusion Overall QoL and recurrence rates were similar between the two modalities. The benefits of RFA do not seem to be enough to overcome the higher costs of HS in Korea.

Modification of a Rodent Hindlimb Model of Secondary Lymphedema: Surgical Radicality versus Radiotherapeutic Ablation

Secondary lymphedema is an intractable disease mainly caused by damage of the lymphatic system during surgery, yet studies are limited by the lack of suitable animal models. The purpose of this study was to create an improved model of secondary lymphedema in the hindlimbs of rodents with sustained effects and able to mimic human lymphedema. This was achieved by combining previously reported surgical methods and radiation to induce chronic lymphedema. Despite more radical surgical destruction of superficial and deep lymphatic vessels, surgery alone was not enough to sustain increased hindlimb volume. Radiotherapy was necessary to prolong these effects, with decreased lymphatic flow on lymphoscintigraphy, but hindlimb necrosis occurred after 4 weeks due to radiation toxicity. The applicability of this model for studies of therapeutic lymphangiogenesis was subsequently tested by injecting muscle-derived stem cells previously cocultured with the supernatant of human lymphatic endothelial cells in vitro. There was a tendency for increased lymphatic flow which significantly increased lymphatic vessel formation after cell injection, but attenuation of hindlimb volume was not observed. These results suggest that further refinement of the rodent hindlimb model is needed by titration of adequate radiation dosage, while stem cell lymphangiogenesis seems to be a promising approach.

Chronic nicotine exposure attenuates proangiogenic activity on human umbilical vein endothelial cells.

The pathogenic mechanism of nicotine, a major product of smoking, on vascular endothelial cells is not well defined yet. The purpose of this study was to determine whether chronic exposure to nicotine alters angiogenic activity in human umbilical vein endothelial cells and to identify a potential role for endothelial nitric oxide synthase (eNOS) expression. Our study demonstrated that acute nicotine treatment enhanced nitric oxide release, eNOS activation, and proangiogenic activity. However, chronic nicotine exposure impaired proangiogenic function (decreased cell migration and tubular structure formation) in human umbilical vein endothelial cells compared with acute exposure, but sustained the antiapoptotic effect. These findings seem to be related to eNOS gene expression and nitric oxide production, which may be involved in the pathophysiology of chronic nicotine addicts.

Role of Laser Doppler for the Evaluation of Pedal Microcirculatory Function in Diabetic Neuropathy Patients.

We evaluated whether LD can detect alterations in skin microcirculatory flow in type II diabetic neuropathy patients and determined which parameters were most predictive.

Recent Advances in the Development of Experimental Animal Models Mimicking Human Aortic Aneurysms.

Aortic aneurysm is a common and life-threatening disease that can cause death from rupture. Current therapeutic options are limited to surgical or endovascular procedures because no pharmacological approaches have been proven to decrease the chance of expansion or rupture. The best approach to the management of aortic aneurysm would be the understanding and prevention of the processes involved in disease occurrence, progression, and rupture. There is a need for animal models that can reproduce the pathophysiological features of human aortic aneurysm, and several such models have been studied. This review will emphasize recent advances in animal models used in the determination of mechanisms and treatments of aortic aneurysms.

Chronological Change of the Sac after Endovascular Aneurysm Repair.

Purpose: The purpose of this study was to evaluate the potential risk factors of type II endoleak and sac growth after endovascular aneurysm repair (EVAR) and the outcomes of secondary interventions. Materials and Methods: Ninety seven patients underwent elective EVAR for infrarenal abdominal aortic aneurysms in two tertiary centers between April 2005 and July 2013. Clinical and imaging parameters were compared among sac growth (>5 mm) and non-growth groups. Risk factors associated with sac growth and persistent type II endoleak were analyzed. The outcomes of reinterventions for persistent type II endoleak were determined. Results: Sac growth was observed in 20 cases (20.6%) and endoleak was found in 90% of them compared to 28.6% (22/77) in the non-growth group (P<0.001). The majority of endoleaks were type II (36/40) and 80.5% were persistent. Sac diameter, neck diameter and number of patent accessory arteries were also statistically significant for sac growth. On multivariate analysis, grade of calcification at the neck, grade of mural thrombus at the inferior mesenteric artery and number of patent accessory arteries were risk factors of persistent type II endoleak. Twenty six reinterventions were done for 16 patients with persistent type II endoleak, with a technical success rate of 88.5%, yet 55.5% showed sac growth regardless of technical success. There were no ruptures during the follow-up period. Conclusion: Sac growth after EVAR was mostly associated with persistent type II endoleak. Secondary interventions using transarterial embolization is partially effective in achieving clinical success.

New routing alternative for proximal anterior tibial artery bypass in patients with Buerger disease

Femoral-anterior tibial artery bypasses with autogenous grafts are difficult to perform when sufficiently long saphenous veins are not available. We performed 12 bypasses on patients with Buerger disease during a 20-year period using a new intermuscular tunneling technique. The graft is passed from the thigh between the muscle compartments without penetrating the muscle fibers, providing an anatomically superior and shorter path. The primary patency rates were 75% at 5 years and 65% at 10 years. We believe that our tunneling technique is safe and durable and might be a viable alternative for proximal femoral-anterior tibial artery bypass in selected patients.