• Journal of Veterinary Science
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• 제24권5호
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• pp.69.1-69.11
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• 2023

Background: Kalkitoxin (KT) is an active lipopeptide isolated from the cyanobacterium Lyngbya majuscula found in the bed of the coral reef. Although KT suppresses cell division and inflammation, KT's mechanism of action in vascular smooth muscle cells (VSMCs) is unidentified. Therefore, our main aim was to investigate the impact of KT on vascular calcification for the treatment of cardiovascular disease. Objectives: Using diverse calcification media, we studied the effect of KT on VSMC calcification and the underlying mechanism of this effect. Methods: VSMC was isolated from the 6 weeks ICR mice. Then VSMCs were treated with different concentrations of KT to check the cell viability. Alizarin red and von Kossa staining were carried out to examine the calcium deposition on VSMC. Thoracic aorta of 6 weeks mice were taken and treated with different concentrations of KT, and H and E staining was performed. Real-time polymerase chain reaction and western blot were performed to examine KT's effect on VSMC mineralization. Calcium deposition on VSMC was examined with a calcium deposition quantification kit. Results: Calcium deposition, Alizarin red, and von Kossa staining revealed that KT reduced inorganic phosphate-induced calcification phenotypes. KT also reduced Ca⁺⁺-induced calcification by inhibiting genes that regulate osteoblast differentiation, such as runtrelated transcription factor 2 (RUNX-2), SMAD family member 4, osterix, collagen 1α, and osteopontin. Also, KT repressed Ca²⁺-induced bone morphogenetic protein 2, RUNX-2, collagen 1α, osteoprotegerin, and smooth muscle actin protein expression. Likewise, Alizarin red and von Kossa staining showed that KT markedly decreased the calcification of ex vivo ring formation in the mouse thoracic aorta. Conclusions: This experiment demonstrated that KT decreases vascular calcification and may be developed as a new therapeutic treatment for vascular calcification and arteriosclerosis.

• Journal of Chest Surgery
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• 제22권2호
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• pp.220-224
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• 1989

In candidates for aortic valve replacement [AVR]it is our primary intention to implant the largest possible vale prosthesis of at least 23 mm in diameter in patients with severe valvular aortic stenosis. However, in many patients there is an additional subvalvular asymmetric septal hypertrophy which in some cases may cause an postextrasystolic increase of the LV-aortic gradient. Another component of the aortic stenosis syndrome is a narrow valvular ring, or a combination of both. After complete removal of the diseased valve and decalcification the narrow aortic ring [< 23 mm] can be widened firstly by transaortic subvalvular septal myectomy- [TSM] thus unfolding the left ventricular outflow tract[LVOT]and secondly by extending the oblique aortic incision into the aortic valve ring or further down into the anterior leaflet of the mitral valve. The sub-and supra-valvular defect will be closed by patch enlargement of the aortic root [PEAR] using autologous pericardium. These techniques allow a considerable enlargement of the valvular ring of about 4 to 10 mm in circumference. In a retrospective study using a computerized program, 847 patients with AVR [1980-1984]were reviewed to evaluate the intraoperative hemodynamic results mainly concerning relief of the transvalvular gradient. In 626 patients AVR was performed, 151 patients had double valve replacement [AVR+MVR], and 70 patients had AVR plus additional surgical procedures. Concentrating on the AVR-group [n=626] there were 103 patients with TSM, 24 patients with PEAR and 20 patients with TSM+PEAR which demonstrated that in a total, of 147 patients of this groups [23.5%] an additional procedure was necessary. The Statistical evaluation of the intraoperative pressure measurements before and after AVR in relation to the size of the implanted prostheses indicated the lowest preoperative mean gradient in patients with AVR alone, the highest in patients who afforded TSM plus PEAR. However, after AVR the mean gradients in all three groups were very low [mean 5 to 10 mmHg]. These data indicate that in patients with a narrow aortic ring and additional considerable ASH, TSM and PEAR are suitable techniques to enlarge the aortic root to enable the implantation of an adequate aortic valve prosthesis. Long-term controls have shown that autologous pericardium is a qualified graft material for the ascending aorta.

• 대한약리학회지
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• 제31권3호
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• pp.285-290
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• 1995

이 실험은 여러 파장$(240{\sim}520\;nm)$의 자외선 또는 가시광선(이후 '광선'이라 표기함)을 흰쥐흉부대동맥에 조사하여 이때의 혈관장력의 변화 및 조직내 cyclic GMP농도의 변화를 관찰하기위하여 시행하였다. 돼지관상동맥 또는 흰쥐 흉부대동맥의 환상표본에 spectrofluorometer의 xenon lamp를 이용하여 여러 파장의 광선을 조사하고 이때의 장력변동을 polygraph상에 기록하였다. Cyclic GMP농도변화는 표본에 광선을 조사한 직후 조직을 얼리고 homogenization 및 원침시킨 후 상청액을 ether로 추출하여 RIA kit로 측정하였다. Phenylephrine으로 수축된 내피존재 흰쥐 흉부 대동맥에서는 광선조사로 수축반응을 보였고 320 nm에서 최대수축반응을 일으켰다. 그 이상의 파장에서는 점차 수축반응이 감소되어 420 nm에서는 최대 이완반응을 일으킨 후 점차 기본장력으로 회복되었다. 그러나 내피제거 표본에서는 전파장에서 이완반응만을 일으켰고 이때 최대 이완반응은 370 nm에서 관찰되었다. 내피존재 표본에서 320, 380 및 420 nm의 광선을 30초간 조사한 결과 380과 420nm에서 현저한 cyclic GMP의 증가가 관찰되었으나 320 nm에서는 유의한 변동이 없었다. 한편, 내피제거 표본에서는370 nm의 광선조사로 cyclic GMP함량이 약 4배 증가하였다. 이상의 성적으로부터 흰쥐 흉부대동맥은 광선조사에 의하여 내피존재 표본에서는 수축-이완의 이상성반응을, 제거표본에서는 이완반응만을 일으키고 양 표본의 이완반응은 nitric oxide-cyclic GMP계의 활성화에 기인하나 수축반응은 cyclic GMP계와 직접 관련성이 없는 것으로 추론하였다.

• The Korean Journal of Physiology
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• 제24권1호
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• pp.77-90
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• 1990

There have been conflicting reports concerning the effect of Panax ginseng on the contractility of vascular smooth muscle, i.e., Panax ginseng extract has been reported to cause relaxation, contraction or to have no effect on the tension of vascular smooth muscle. A further investigation of $Ca^{++}$ stores which supply $Ca^{++}$ for contraction of vascular smooth muscle is needed to understand the underlying mechanisms of this conflicting effect of ginseng alcohol extract (GAE). The present study was intended to examine the sources of calcium mobilized for contraction of vascular smooth muscle by GAE. Aortic ring preparations were made from the rabbit thoracic aorta and endothelial cells were removed from the ring. The contractility of the aortic ring was measured under various experimental conditions and $Ca^{++}$ flux across the membrane of aortic ring and the sarcoplasmic reticulum and mitochondria were measured with a calcium selective electrode. The result were summarized as follows; 1) At low concentration of extracellular $Ca^{++}$, GAE increased the contractility of vascular smooth muscle in dose-dependent fashion except high concentration $Ca^{++}$ (1 mM). 2) In the presence of ryanodine, GAE still increased contractility of vascular smooth muscle as much as control group, but in the presence of caffeine, GAE increased it significantly. i.e. Their effects seemed to be additive. 3) In the presence of verapamil+lanthanum, and verapamil+lanthanum+ryanodine, the contractility of the vascular smooth muscle was decreased, but a dose dependent increase in vascular tension was still demonstrated by GAE although total tension was low. 4) GAE increased $Ca^{++}$ efflux from vascular smooth muscle cells, but have no effect on $Ca^{++}$ influx. 5) GAE increased $Ca^{++}$ efflux from sarcoplasmic reticulum and mitochondria vesicles. From the above results, it may be concluded that GAE increased the release of $Ca^{++}$ from sarcoplasmic reticulum, mitochondria or other intracellular $Ca^{++}$ stores of vascular smooth muscle, but it does not increase $Ca^{++}$ influx across the plasma membrane.

• BMB Reports
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• 제49권3호
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• pp.191-196
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• 2016

Vascular endothelial growth factor (VEGF) is a key mediator of angiogenesis and critical for normal embryonic development and repair of pathophysiological conditions in adults. Although phospholipase D (PLD) activity has been implicated in angiogenic processes, its role in VEGF signaling during angiogenesis in mammals is unclear. Here, we found that silencing of PLD2 by siRNA blocked VEGF-mediated signaling in immortalized human umbilical vein endothelial cells (iHUVECs). Also, VEGF-induced endothelial cell survival, proliferation, migration, and tube formation were inhibited by PLD2 silencing. Furthermore, while Pld2-knockout mice exhibited normal development, loss of PLD2 inhibited VEGF-mediated ex vivo angiogenesis. These findings suggest that PLD2 functions as a key mediator in the VEGF-mediated angiogenic functions of endothelial cells.

• 동의생리병리학회지
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• 제23권2호
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• pp.389-396
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• 2009

The ethanol extract of Persicaria perfoliata (EPP) induced relaxation of the phenylephrine-precontracted aorta in a dose-dependent manner, which was abolished by removal of functional endothelium. Pretreatment of the aortic tissues with NG-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2,4}-oxadiazole-[4,3-${\alpha}$)-quinixalin-1-one (ODQ) inhibited the relaxation induced by EPP. However, EPP-induced relaxation was not blocked by pretreatment with indomethacine, glibenclamide, tetraethylammonium (TEA), atropine, or propranolol. Incubation of endothelium-intact thoracic aortic ring with EPP increased the production of cGMP, which was also blocked by pretreatment with L-NAME or ODQ. These results suggest that EPP dilates vascular smooth muscle via endothelium-dependent NO/cGMP signaling.

• Preventive Nutrition and Food Science
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• 제19권4호
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• pp.299-306
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• 2014

Hesperetin has been shown to possess a potential anti-angiogenic effect, including vascular formation by endothelial cells. However, the mechanisms underlying the potential anti-angiogenic activity of hesperetin are not fully understood. In the present study, we evaluated whether hesperetin has anti-angiogenic effects in human umbilical vascular endothelial cells (HUVECs). HUVECs were treated with 50 ng/mL vascular endothelial growth factor (VEGF) to induce proliferation as well as vascular formation, followed by treatment with several doses of hesperetin (25, 50, and $100{\mu}M$) for 24 h. Cell proliferation and vascular formation were analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and tube formation assay, respectively. In addition, cell signaling related to cell proliferation and vascular formation was analyzed by western blot. Furthermore, a mouse aorta ring assay was performed to confirm the effect of hesperetin on vascular formation. Hesperetin treatment did not cause differences in HUVECs proliferation. However, hesperetin significantly inhibited VEGF-induced cell migration and tube formation of HUVECs (P<0.05). Moreover, hesperetin suppressed the expression of ERK, p38 MAPK, and PI3K/AKT in the VEGF-induced HUVECs. In an ex vivo model, hesperetin also suppressed microvessel sprouting of mouse aortic rings. Taken together, the findings suggest that hesperetin inhibited vascular formation by endothelial cells via the inhibition of the PI3K/AKT, ERK and p38 MAPK signaling.

• 한국임상수의학회지
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• 제35권1호
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• pp.26-29
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• 2018

A 6-month-old, female poodle presented with a three-month history of persistent regurgitation immediately after eating. On physical examination, the patient was emaciated and dehydrated. Thoracic radiography showed ventral displacement of the trachea and increased radiopacity in the mediastinum, cranial to the heart base. A severely dilated esophagus was identified cranial to the heart on esophagram. Computed tomography (CT) revealed the esophagus was filled with gas, fluid and a little of contrast and dilated from caudo-cervical to cranio-thoracic part. The esophageal diameter was markedly decreased at the heart base. In addition, the trachea was displaced to the left-ventral side of the right aortic trunk and an aberrant left subclavian artery originating from the aorta was identified. There was no evidence of abdominal vascular anomaly. Based on diagnostic imaging, persistent right aortic arch (PRAA) with an aberrant left subclavian artery was diagnosed. The patient did not undergo surgery and died at 15 days after diagnosis. This report describes imaging diagnosis, including CT and radiography in a weaned dog with regurgitation due to esophageal obstruction by PRAA. When PRAA is suspected and conventional radiography or contrast study is insufficient for diagnosis, CT may be helpful for diagnosing PRAA.

• 대한약리학회지
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• 제26권2호
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• pp.135-144
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• 1990

Propylthiouracil(PTU)을 4주 및 12주간 투여한 흰쥐의 대동맥을 적출하여 혈관수축제와 이완제에 대한 반응을 관찰하여 다음과 같은 결과를 얻었다. PTU를 처치한 실험군에서는 대조군에 비해 현저한 체중저하와 혈중 갑상선호르몬의 감소를 보였다. PTU를 처치한 흰쥐의 대동맥에 대한 norepinephrine (NE)과, calcium및 potassium 이온에 의한 최대수축 반응은 대조군에 비하여 유의하게 감소되었다. 그러나 NE에 대한 중간유효량은 증가되었으나, calcium이온에 대한 중간 유효량은 유의한 차이가 없었다. 그리고 acetylcholine, histamine, isoproterenol 및 nitroprusside에 의한 대동맥의 이완작용은 대조군에 비해 증가된 경향을 보였다. PTU를 12주간 처치한 군에 있어서 acetylcholine에 의한 최대 이완반응은 대조군에 비해 유의하게 증가되었지만 다른 이완제에 의해서는 유의한 차이가 없었다. PTU를 4주간 처치한 군에 있어서는 대조군에 비하여 혈관이완제에 대한 중간억제량은 유의한 차이가 없었지만, 12주 처치군에 있어서는 isoproterenol 및 nitroprusside에 대한 중간억제량은 감소 되었으나 acetylcholine 및 histamine에 대한 중간억제량은 유의한 차이가 없었다. 이상의 결과로 미루어 보아 PTU-처치에 의한 혈관 반응성의 변화는 혈관 내피세포보다는 혈관 평활근세포자체의 변화에 기인되며, 이러한 세포내의 변화는 갑상선 기능이 저하된 후에도 계속되고 있음을 알 수 있었다.

• Journal of Chest Surgery
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• 제42권6호
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• pp.749-756
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• 2009

배경: 혈관륜은 대동맥궁의 드문 기형으로 저자들이 12년 간 경험한 16예의 수술 결과를 정리하여 그 경험을 공유하고자 한다. 대상 및 방법: 1995년 11월부터 2007년 9월까지 혈관륜으로 수술을 받은 16명을 대상으로 하여 이중 대동맥궁(n=5), 우측 대동맥궁-동맥관 인대(n=7), 폐동맥 슬링(n=4)의 세 가지 그룹으로 분류하였다. 각 그룹의 수술 당시 평균 연령은 이중 대동맥궁 그룹에서 $5.7{\pm}5.5$세, 우측 대동맥궁-동맥관 인대 그룹에서 $6.1{\pm}13.4$세, 폐동맥 슬링 그룹에서 $2.9{\pm}2.6$세였다. 우측 대동맥궁-동맥관 인대 그룹의 71% (n=5)에서 Kommerell 게실이 동반되어 있었다. 기관 협착은 이중 대동맥궁 그룹 중 2예(40%), 우측 대동맥궁-동맥관 인대 그룹 중 2예(28.6%), 폐동맥 슬링 그룹 중 4예 (100%)에서 동반되어 있었다. 함께 진단된 심장 기형은 전체의 50% (n=8)였다. 결과: 사망한 예는 없었고, 증상 재발 및 문합부 협착 등으로 재수술을 시행한 예도 없었다. 평균 재원 기간은 $27.1{\pm}38.2$일이었다. 결론: 혈관륜은 드문 질환이지만 수술적 교정이 필요하므로, 원인이 명확하지 않은 호흡기 증상이 반복될 경우에는 심초음파 등으로 반드시 확인해 보아야 하며, 수술 전후의 전산화 단층촬영 및 기관지 내시경은 기도 협착 및 주변 해부학적 구조와의 관계 평가에 유용하게 이용할 수 있다.