Roles of Vascular Smooth Muscle Cells in Atherosclerotic Calcification

The accumulation of calcium in atherosclerotic plaques is a prominent feature of advanced atherosclerosis, and it has a strong positive correlation with the total burden of atherosclerosis. Atherosclerotic calcification usually appears first at the necrotic core, indicating that cell death and inflammatory processes are involved in calcification. During atherosclerotic inflammation, various cell types, such as vascular smooth muscle cells, nascent resident pericytes, circulating stem cells, or adventitial cells, have been assumed to differentiate into osteoblastic cells, which lead to vascular calcification. Among these cell types, vascular smooth muscle cells are considered a major contributor to osteochondrogenic cells in the atherosclerotic milieu. In this review, we summarize the molecular mechanisms underlying the osteochondrogenic switch of vascular smooth muscle cells in atherosclerotic plaques.

Deciphering Macrophage Phenotypes upon Lipid Uptake and Atherosclerosis

In the progression of atherosclerosis, macrophages are the key immune cells for foam cell formation. During hyperlipidemic condition, phagocytic cells such as monocytes and macrophages uptake oxidized low-density lipoproteins (oxLDLs) accumulated in subintimal space, and lipid droplets are accumulated in their cytosols. In this review, we discussed the characteristics and phenotypic changes of macrophages in atherosclerosis and the effect of cytosolic lipid accumulation on macrophage phenotype. Due to macrophage plasticity, the inflammatory phenotypes triggered by oxLDL can be re-programmed by cytosolic lipid accumulation, showing downregulation of NF-κB activation followed by activation of anti-inflammatory genes, leading to tissue repair and homeostasis. We also discuss about various in vivo and in vitro models for atherosclerosis research and next generation sequencing technologies for foam cell gene expression profiling. Analysis of the phenotypic changes of macrophages during the progression of atherosclerosis with adequate approach may lead to exact understandings of the cellular mechanisms and hint therapeutic targets for the treatment of atherosclerosis.

Involvement of immune responses in pulmonary arterial hypertension; lessons from rodent models / 한국실험동물학회지

Pulmonary hypertension (PH) is a pathological state with sustained elevation of pulmonary artery (PA) pressure. Since the pathogenesis of PH is mostly irreversible, the disease often comes up with poor prognosis. Pulmonary arterioles are affected by deteriorative changes, such as development of occlusive lesions of thickening of arterial walls. Such processes increase the pulmonary arterial pressure thus lead to consequent injuries such as right ventricle failure. Proliferation, or resistance to apoptosis of pulmonary artery smooth muscle cells (PASMC) and fibroblasts, are characteristic changes observed in the PA in pulmonary arterial hypertension (PAH) patients. PAH can either occur idiopathically or come with other diseases. Emerging evidences suggest that pro-inflammatory processes are closely related to the development of PAH. Therefore, it is inferred that immune cells could be the key factors in PAH development. In this review, we summarize the way how each types of immune cells participate in PAH. We would also like to list the current rodent models used for PAH study.

Clinical Results of Subtotal Fasciectomy for Treatment of Dupuytren Contracture / 대한정형외과학회잡지

PURPOSE: In the treatment of Dupuytren's contracture, the aim of optical treatment is to lower the recurrence rate and reduce complications. This paper reports the results of subtotal fasciectomy in Dupuytren's contracture, extending the excision of palmar fascial structures from the diseased to normal appearing adjacent fascial structure. MATERIALS AND METHODS: From 2007 to 2017, 45 patients with Dupuytren's contracture treated by subtotal fasciectomy were reviewed retrospectively. The mean follow-up period was 45.9 months. Ninety-two digits were involved (index: 2, middle: 10, ring: 44, little: 36). The predisposing factors and affected joint were reviewed and the preoperative and postoperative contracture was measured. For clinical results, quick disabilities of the arm, shoulder, and hand (quick DASH) were used. Complications, including wound or skin problems, nerve injuries, hematoma, and complex regional pain syndrome, were assessed. RESULTS: Preoperative flexion contracture was 43.2° in the proximal interphalangeal joint and 32.9° in the metacarpophalangeal joint. In nine cases, patients had residual contracture of 9.7° (range, 5°–20°) on average and if the total number of cases were included, the mean residual contracture was 2.3° on average. The quick DASH score at the 12 months follow-up was 12.4. The overall complication rate was 26.6%. CONCLUSION: Subtotal fasciectomy can be a good surgical treatment option for Dupuytren's contracture with a low recurrence and low complication rate compared to other open procedures.

A Comparison of the Results between Internal Fixation and External Fixation in AO C Type Distal Radius Fractures

PURPOSE: The purpose of this study was to evaluate the radiological and clinical results of plate fixation and external fixation with additional devices for treating distal radius fracture in AO type C subtypes, and propose a treatment method according to the subtypes. MATERIALS AND METHODS: Two hundred and one AO type C distal radius fracture patients were retrospectively reviewed. Eighty-five patients in group 1 were treated with volar or dorsal plate, and 116 patients in group 2, were treated with external fixation with additional fixation devices. Clinical (range of mtion, Green and O'Brien's score) and radiological outcomes were evaluated. RESULTS: At the 12-month follow-up, group 1 showed flexion of 64.4°, extension of 68.3°, ulnar deviation of 30.6°, radial deviation of 20.8°, supination of 76.1°, and pronation of 79.4° in average; group 2 showed flexion of 60.5°, extension of 66.9°, ulnar deviation of 25.5°, radial deviation of 18.6°, supination of 73.5°, and pronation of 75.0° in average. The mean Green and O'Brien score was 92.2 in group 1 and 88.6 in group 2. The radial height of group 1 and group 2 was 11.6/11.4 mm; radial inclination was 23.2°/22.5°; volar tilt was 11.6°/8.7°; and the ulnar displacement was 1.27/0.93 mm. CONCLUSION: Judicious surgical techniques during device application and tips for postoperative management during external fixation can produce similar clinical results compared with internal fixation patients.

Collagen-Induced Arthritis Analysis in Rhbdf2 Knockout Mouse

Rhomboid family member 2 gene (Rhbdf2) is an inactive homologue lacking essential catalytic residues of rhomboid intramembrane serine proteases. The protein is necessary for maturation of tumor necrosis factor-alpha (TNF-α) converting enzyme, which is the molecule responsible for the release of TNF-α. In this study, Rhbdf2 knockout (KO) mice were produced by CRISPR/CAS9. To see the effects of the failure of TNF-α release induced by Rhbdf2 gene KO, collagen-induced arthritis (CIA), which is the representative TNF-α related disease, was induced in the Rhbdf2 mutant mouse using chicken collagen type II. The severity of the CIA was measured by traditional clinical scores and histopathological analysis of hind limb joints. A rota-rod test and grip strength test were employed to evaluate the severity of CIA based on losses of physical functions. The results indicated that Rhbdf2 mutant mice showed clear alleviation of the clinical severity of CIA as demonstrated by the significantly lower severity indexes. Moreover, a grip strength test was shown to be useful for the evaluation of physical functional losses by CIA. Overall, the results showed that the Rhbdf2 gene has a significant effect on the induction of CIA, which is related to TNF-α.

Inflammation induces two types of inflammatory dendritic cells in inflamed lymph nodes

The spatiotemporal regulation of immune cells in lymph nodes (LNs) is crucial for mounting protective T-cell responses, which are orchestrated by dendritic cells (DCs). However, it is unclear how the DC subsets are altered by the inflammatory milieu of LNs. Here, we show that the inflamed LNs of Listeria-infected mice are characterized by the clustering of neutrophils and monocytes and IFN-γ production. Significantly, the early inflammatory responses are coupled with the differentiation of not one, but two types of CD64⁺CD11c⁺MHCII⁺ inflammatory DCs. Through the assessment of chemokine receptor dependency, gene expression profiles, growth factor requirements and DC-specific lineage mapping, we herein unveil a novel inflammatory DC population (we termed ‘CD64⁺ cDCs’) that arises from conventional DCs (cDCs), distinguishable from CD64⁺ monocyte-derived DCs (moDCs) in inflamed LNs. We determined that Listeria-induced type I IFN is a critical inflammatory cue for the development of CD64⁺ cDCs but not CD64⁺ moDCs. Importantly, CD64⁺ cDCs displayed a higher potential to activate T cells than CD64⁺ moDCs, whereas the latter showed more robust expression of inflammatory genes. Although CD64⁺ and CD64− cDCs were able to cross-present soluble antigens at a high dose to CD8⁺ T cells, CD64⁺ cDCs concentrated and cross-presented a minute amount of soluble antigens delivered via CD64 (FcγRI) as immune complexes. These findings reveal the role of early inflammatory responses in driving the differentiation of two inflammatory DC subsets empowered with distinct competencies.

Involvement of Immune Cell Network in Aortic Valve Stenosis: Communication between Valvular Interstitial Cells and Immune Cells

Aortic valve stenosis is a heart disease prevalent in the elderly characterized by valvular calcification, fibrosis, and inflammation, but its exact pathogenesis remains unclear. Previously, aortic valve stenosis was thought to be caused by chronic passive and degenerative changes associated with aging. However, recent studies have demonstrated that atherosclerotic processes and inflammation can induce valvular calcification and bone deposition, leading to valvular stenosis. In particular, the most abundant cell type in cardiac valves, valvular interstitial cells, can differentiate into myofibroblasts and osteoblast-like cells, leading to valvular calcification and stenosis. Differentiation of valvular interstitial cells can be trigged by inflammatory stimuli from several immune cell types, including macrophages, dendritic cells, T cells, B cells, and mast cells. This review indicates that crosstalk between immune cells and valvular interstitial cells plays an important role in the development of aortic valve stenosis.

Management of Split Thickness Skin Graft Donor Site: Comparison of Different Biologic Dressing Materials (Kaloderm® vs Xe-derma®)

PURPOSE: With the advances of knowledge in wound healing process and technology in various fields, dressing material of the split thickness skin graft (STSG) donor site was improved. Recently, biologic dressing materials attracted attention and these are used for wound management. The aim of the study was to compare the efficacy of Xe-derma® (porcine acellular dermal matrix) with Kaloderm® (cultured epithelial autografts) for treatment of the donor site. METHODS: From July 2015 to January 2016, 20 patients who had undergone STSG were enrolled. The grafts harvested with a same manner and the donor sites were managed with Xe-derma® or Kaloderm®. We compared days for re-epithelization, number of dressings, ease of application, ease of wound monitoring, pain level and complications. RESULTS: All patients managed by these dressing materials were well healed without any complications. There is no statistically difference (P=0.830) between the days for re-epithelization of Xe-derma® (11.10±0.944) and Kaloderm® (11.00±1.054). Number of dressings of Xe-derma® (1.2±0.421) was lower than Kaloderm® (2.3±0.483). Ease of application of Kaloderm® (7.40±0.516) was easier than Xe-derma® (6.36±0.343). Ease of wound monitoring of Xe-derma® (7.77±0.856) was easier than Kaloderm® (6.25±0.720). Xe-derma® was more painless in 1 day and 3 days after operation than Kaloderm®. CONCLUSION: Advantageous properties of Xe-derma® are improving wound healing, reducing pain by contact to the wound immediately after application and easy of wound monitoring due to its transparency. Therefore, we expected Xe-derma® can be used for management of various wound.

Effect of an Ibuprofen Releasing Dressing (Biatain Ibu®) on Skin Graft Donor Site Wound Pain

PURPOSE: The purpose of management of split thickness skin graft (STSG) donor site is to promote healing process and minimize pain and infection. There are many dressing materials for managing donor site. The study aimed to compare the effect on management of donor site between Biatain Ibu® (polyurethane foam with incorporated ibuprofen) and Mepilex® (polyurethane foam coated with silicone). Especially, we focused on manage of donor site pain and treatment satisfaction. METHODS: This prospective study was conducted on 30 patients underwent STSG from January 2015 to June 2015. The grafts harvested with a same manner and the donor sites were managed with Biatain Ibu® or Mepilex®. Donor site pain, treatment satisfaction, days for re-epithelization and complication were compared between the two groups. RESULTS: All of 30 patients were well healed and there was no complications. Pain level of Biatain Ibu® (2.32±0.929) was lower than Mepilex® (4.77±1.224). Treatment satisfaction of Biatain Ibu® (8.40±0.632) was higher than Mepilex® (7.33±0.487). There is no statistically differences (P=0.455) in the days for re-eopithelization between Biatain Ibu® (14.73±0.789) and Mepilex® (14.53±0.639). CONCLUSION: The Biatain Ibu® dressing represents a valuable alternative in the management of STSG donor site by providing an appropriate wound healing, reduction of pain and improving treatment satisfaction.

Effect of Wound Healing by Physiotulle® in Donor Site of Split-Thickness Skin Graft

PURPOSE: Split thickness skin graft (STSG) is frequently used for reconstructing wounds. The treatment of split-thickness donor sites demands several factors: maintenance a moist condition, minimization of pain, promotion of re-epithelization and ease of care. We have performed a study to evaluate efficacy of Physiotulle® for donor site management. METHODS: A prospective study was conducted from June 2015 to December 2015 and included 20 patients undergoing surgery for reconstructive purposes with the use of STSG. The grafts harvested with a same manner and the donor sites were managed with one of the two dressing material: Physiotulle® or Bactigras®. We campared post-operative pain scale, bleeding of donor site, period of re-epithelization and donor site infection. RESULTS: All of 20 patients were well healed after application of Physiotulle® or Bactigras® dressing without any complications. Pain level was similar between two groups until 3 days after operation but Physiotulle® (4.1±0.233) showed significant (P<0.01) pain increasing on 7 days after operation compared with Bactigras® (2.9±0.277). The bleeding index score on 7 days after operation of Physiotulle® (2.5±0.167) was higher than Bactigras® (2.0±0.211) but there is no difference. Statistically (**P<0.01), the period of re-eopithelization of Physiotulle® (13.50±0.87) was significantly shorten than Bactigras® (17.25±0.65). CONCLUSION: Physiotulle® is effective in re-epithelization. We recommend applying ointment on donor site when exudate is minimized, about 7 days after operation to prevent aggravation of pain and bleeing of donor site.

A Case of Non ST Elevation Myocardial Infarction by Coronary Artery Focal Spasm in a Patient with Autosomal Dominant Polycystic Kidney Disease

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disease. The main causes of death in ADPKD are cardiovascular disease as well as infections and neurological reasons. ADPKD is causing vasculopathy including aortic root dilation, cerebral artery aneurysm, coronary aneurysm, and aortic dissection. In this case report, we describe a 37-year-old female ADPKD patient with non-ST elevation MI (NSTEMI) caused by coronary artery focal spasm.

Ganglion Cyst of the Sternoclavicular Joint in an Adult

Ganglion cysts are most common on the dorsum of the hand or wrist, but they can occur in any part of the body. There have been few papers reporting ganglion cysts originating from the sternoclavicular joint, with most of these cases developing in children. A 76-year-old woman was referred to our department because of a painless mass over the right sternoclavicular joint. The mass was excised along with the portion of the sternoclavicular joint capsule surrounding the stalk. Histopathologic examination showed the cyst wall to be composed of compressed collagen fibers without evidence of an epithelial or synovial lining, which was consistent with ganglion cyst. To our knowledge, this is the first report of such a cyst in an adult. We consider this to be a useful report for surgeons that treat mass lesions occurring in almost any part of the body surface.

Negative Pressure Pulmonary Edema Together with Pneumopericardium after General Anesthesia / 대한내과학회지

Negative pressure pulmonary edema is an uncommon complication related to general anesthesia. Its main pathophysiology is excessive negative intrathoracic pressure that is caused by an acute upper airway obstruction. Pneumopericardium, the presence of air within the pericardial sac, is another rare condition. The common pathophysiology of pneumopericardium, except for that caused by blunt or penetrating trauma, is barotrauma-induced alveolar rupture caused by positive intrathoracic pressure. Here, we report the case of a 61-year old female patient with negative pulmonary edema and pneumopericardium after general anesthesia. She recovered after conservative management.

Acute Upper Limb Ischemia Suspected to Have Originated from Staphylococcus Epidermidis Native Valve Endocarditis / 대한내과학회지

We report a case of acute upper limb ischemia suspected to have originated from methicillin-resistant Staphylococcus epidermidis native valve endocarditis in a 57-year-old man who had complained of sudden-onset fever and pain in the right hand. 3D computed tomography of the right upper extremity detected a thrombus occluding the brachial artery. Echocardiography showed a large vegetation on the aortic valve. Thus, we suspected, clinically, brachial artery occlusion by septic emboli originating from a large vegetation of the aortic valve. The patient was treated with intravenous antibiotics for the suspected methicillin-resistant Staphylococcus epidermidis-native valve endocarditis with a combination of percutaneous aspiration thromboembolectomy and selective intra-arterial thrombolysis for acute thromboembolic occlusion in the right upper limb. The large vegetation of the aortic valve resolved without surgery and aortic regurgitation improved. The patient recovered uneventfully with no complications, including septic embolism, over the following 11 months.

Free Flap Reconstruction of Head and Neck Defects after Oncologic Ablation: One Surgeon's Outcomes in 42 Cases

BACKGROUND: Free flap surgery for head and neck defects has gained popularity as an advanced microvascular surgical technique. The aims of this study are first, to determine whether the known risk factors such as comorbidity, tobacco use, obesity, and radiation increase the complications of a free flap transfer, and second, to identify the incidence of complications in a radial forearm free flap and an anterolateral thigh perforator flap. METHODS: We reviewed the medical records of patients with head and neck cancer who underwent reconstruction with free flap between May 1994 and May 2012 at our department of plastic and reconstructive surgery. RESULTS: The patients included 36 men and 6 women, with a mean age of 59.38 years. The most common primary tumor site was the tongue (38%). The most commonly used free flap was the radial forearm free flap (57%), followed by the anterolateral thigh perforator free flap (22%). There was no occurrence of free flap failure. In this study, risk factors of the patients did not increase the occurrence of complications. In addition, no statistically significant differences in complications were observed between the radial forearm free flap and anterolateral thigh perforator free flap. CONCLUSIONS: We could conclude that the risk factors of the patient did not increase the complications of a free flap transfer. Therefore, the risk factors of patients are no longer a negative factor for a free flap transfer.

Redoable Tie-Over Dressing Using Multiple Loop Silk Threads

After skin grafting, to prevent hematoma or seroma collection at the graft site, a tie-over dressing has been commonly used. However, although the conventional tie-over dressing by suture is a useful method for securing a graft site, refixation is difficult when repeated tie-over dressing is needed. Therefore, we recommend a redoable tie-over dressing technique with multiple loops threads and connecting silk threads. After the raw surface of each of our cases was covered with a skin graft, multiple loop silk thread attached with nylon at the skin graft margin. We applied the ointment gauze and wet cotton/fluffy gauze over the skin graft, then fixed the dressing by connecting cross-counter multiple loop thread with connecting silk threads. When we opened the tie-over dressing by cutting the connecting silk threads, we repeated the tie-over dressing with the same method. The skin graft was taken successfully without hematoma or seroma collection or any other complications. In conclusion, we report a novel tie-over dressing enabling simple fixation of the dressing to maintain proper tension for wounds that require repetitive fixation. Further, with this reliable method, the skin grafts were well taken.

A Case of Acroosteolysis in Primary Hypertrophic Osteoarthropathy

Primary hypertrophic osteoarthropathy or pachydermoperiostosis is a rare hereditary disorder characterized by digital clubbing, pachydermia and periostosis. Its precise incidence and prevalence is still unknown due to the lack of controlled data. It occurs without any underlying causes and usually has a chronic course. Life expectancy may be of normal standards, but many patients develop multiple functional and cosmetic complications. So, it is important to diagnose this disease at an early stage and to treat the symptomat for the quality of life. We report a case of primary hypertrophic osteoarthropathy in a 68-year-old male with clinical features such as digital clubbing and pachydermia, radiographic findings of acroosteolysis and periosteal new bone formation.

Current Understanding of Dendritic Cells in Atherosclerosis / 한양의대학술지

Dendritic cells (DCs), first identified in 1973, have been shown to be the principal cells involved in antigen presentation to T cells, and are more potent in the presentation of antigen than B cells or macrophages. Atherosclerosis is a representative chronic vascular inflammatory disease in which various immune cells have been implicated in the formation of atherosclerotic plaque. Thus, the quantification and elucidation of activity of immune populations in atherosclerotic vessels are very important in understanding the pathogenesis of atherosclerosis. Several current studies demonstrate that DCs which exist in atherosclerotic lesion appear to play several important roles in atherosclerosis. This review summarizes current understandings on the function of DCs in atherosclerosis, and also suggests future directions for research of DC function in inflammatory atherosclerotic vascular disease.

KR-31543 reduces the production of proinflammatory molecules in human endothelial cells and monocytes and attenuates atherosclerosis in mouse model

KR-31543, (2S, 3R, 4S)-6-amino-4-[N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl) amino]-3,4-dihydro-2-dimethyoxymethyl-3-hydroxy-2-methyl-2H-1-benz opyran is a new neuroprotective agent for ischemia-reperfusion damage. It has also been reported that KR-31543 has protective effects on lipid peroxidation and H2O2-induced reactive oxygen species production. In this study, we investigated the anti-inflammatory and anti-atherogenic properties of KR-31543. We observed that KR-31543 treatment reduced the production of MCP-1, IL-8, and VCAM-1 in HUVECs, and of MCP-1 and IL-6 in THP-1 human monocytes. We also examined the effect of KR-31543 on monocytes migration in vitro. KR-31543 treatment effectively reduced the migration of THP-1 human monocytes to the HUVEC monolayer in a dose-dependent manner. We next examined the effects of this compound on atherogenesis in LDL receptor deficient (Ldlr-/-) mice. After 10 weeks of western diet, the formation of atherosclerotic lesion in aorta was reduced in the KR-31543-treated group compared to the control group. The accumulation of macrophages in lesion was also reduced in KR-31543 treated group. However, the plasma levels of total cholesterol, HDL, LDL, and triglyceride were not affected by KR-31543 treatment. Taken together, these results show that KR-31543 has anti-inflammatory properties on human monocytes and endothelial cells, and inhibits fatty streak lesion formation in mouse model of atherosclerosis, suggesting the potential of KR-31543 for the treatment for atherosclerosis.