• Nutrition Research and Practice
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• 제14권4호
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• pp.322-333
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• 2020

BACKGROUND/OBJECTIVES: Arterial stiffness and endothelial dysfunction are 2 of the independent predictors for cardiovascular disease, while Acanthopanax senticosus Harms (ASH) is a traditional medicinal plant that can improve cardiovascular health. This study aimed to investigate the efficacy of the fruit of ASH on vascular function in apparently healthy subjects. SUBJECTS/METHODS: A 12-week, randomized, double-blind, placebo-controlled design, consisting of healthy adults with at least 2 of the following 3 conditions: borderline high blood pressure (BP; 120 mmHg ≤ systolic BP ≤ 160 mmHg or 80 mmHg ≤ diastolic BP ≤ 100 mmHg), smoking (≥10 cigarettes/day), and borderline blood lipid levels (220 ≤ total cholesterol ≤ 240, 130 ≤ low density lipoprotein cholesterol ≤ 165, or 150 ≤ triglyceride ≤ 220 mg/dL). Randomly assigned 76 subjects who received a placebo or 2 doses of ASH fruit (low, 500 mg/day; high, 1,000 mg/day) completed the intervention. Brachial-ankle pulse wave velocity (baPWV), flow-mediated dilation, carotid intima-media thickness, and BP were measured both at baseline and following the 12-week intervention. Endothelial nitric oxide synthase (eNOS) phosphorylation was assessed by western blotting. RESULTS: Compared with the placebo group, the low-dose group showed more significant changes after the 12-week intervention period in terms of systolic BP (0.1 vs. -7.7 mmHg; P = 0.044), baPWV (31.3 vs. -98.7 cm/s; P = 0.007), and the ratio of phospho-eNOS/eNOS (0.8 vs. 1.22; P = 0.037). CONCLUSIONS: These results suggest that ASH fruit extract at 500 mg/day has the potential to improve BP and arterial stiffness via endothelial eNOS activation in healthy adults with smoking and the tendency of having elevated BP or blood lipid parameters.

• Journal of Yeungnam Medical Science
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• 제25권1호
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• pp.41-49
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• 2008

한탄바이러스가 혈소판활성인자 활성에 영향을 미치는지 알아보기 위하여 간접적으로 혈소판활성인자 수용체의 발현과 분해효소의 활성을 측정하였다. 혈관내피세포에서 혈소판활성인자 수용체의 유전자를 역전사 중합효소연쇄반응으로, 단백질은 western blot으로 측정하였다. 또한 세포표면에 발현된 혈소판활성인자 수용체의 양은 FACS로 분석하였다. 한탄바이러스에 감염된 혈관내피세포에서 혈소판활성인자 수용체의 유전자, 단백질, 세포 표면의 발현 모두 바이러스에 감염되지 않은 대조 세포보다 감염 후 2, 3일째 증가 하였다. 혈액 내 혈소판활성인자 분해효소의 활성을 비교한 결과 신증후출혈열 환자에서 정상인에 비하여 2.5배 낮았다. 그리고 신증후출혈열 환자가 회복됨에 따라 혈소판활성인자의 활성이 다시 정상 수준으로 회복되는 것으로 나타났다. 따라서 한탄바이러스에 의해 증가된 혈소판활성인자 수용체의 발현이 혈소판활성인자와 혈관내피세포와 반응성을 증가시키고, 신증후출혈열 환자 혈액에서 감소된 혈소판활성인자 분해효소가 혈소판활성인자의 분해를 지연 시켜 작용시간을 증가 시킴으로써 과다한 혈소판활성인자의 생물학적 작용이 신증후출혈열의 병리현상을 초래할 것으로 사료된다.

• 대한한방내과학회지
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• 제26권3호
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• pp.575-586
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• 2005

FC(free choresterol) plays an important role in normal and pathophysiological cells including that of messenger molecule or dilator of blood vessels in such illnesses as artheriosclerosis, hypertension and myocardial infarction. Smooth muscle and endothelial cell functions in the arteria wall are unified by complex intercellular signalling processes. In arteria comprised of one layer of smooth muscle cells surrounding the endothelium, the close apposition of the two cell types enables a signal derived from one cell to rapidly diffuse to neighboring cells. Experimentation was conducted to investigate the potential contribution of Sohaphyangwon(SHHW) on levels of FC generated by goaded microphages, and mechanisms of protection against ACAT inhibitor. It was found that J774 macrophages, which normally do not express FC were expressed by oxLDL and ACAT inhibitor. SHHW protected cells were found to be resistant to oxLDL and delayed death following the FC. Inhibition of FC formation abolished the protective effect against ACAT inhibitor exposure. Cadiovascular diseases include abnormalities of blood vessels dysfunction of the renin-angiotension system. What relation herbal medicine may have with vessel endothelium necrosis was here studied. In Oriental Medicine, SHHW water extract used for diseases in relation to cardiovascular systems. The resistence to cardiovascular disease of ACAT inhibitor induced J774 macrophage cells were studied through analysis of cell morphological patterns and immunochemistry of SHHW. The results of this study suggest that SHHW has protective effects on the cardiovascular system, and that it is effective in both prevention and treatment of diseases of the cardiovascular system, particularity against necrosis of blood.

• Journal of Chest Surgery
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• 제46권1호
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• pp.14-21
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• 2013

Background: Reactive oxygen species (ROS) are known to be related to cardiovascular diseases. Many studies have demonstrated that angiotensin-converting enzyme inhibitors have beneficial effects against ROS. We investigated the antioxidant effect of captopril and enalapril in nitric oxide mediated vascular endothelium-dependent relaxations. Materials and Methods: Isolated rabbit abdominal aorta ring segments were exposed to ROS by electrolysis of the organ bath medium (Krebs-Henseleit solution) after pretreatment with various concentrations (range, $10^{-5}$ to $3{\times}10^{-4}$ M) of captopril and enalapril. Before and after electrolysis, the endothelial function was measured by preconstricting the vessels with norepinephrine ($10^{-6}$ M) followed by the cumulative addition of acetylcholine (range, $3{\times}10^{-8}$ to $10^{-6}$ M). The relevance of the superoxide anion and hydrogen peroxide scavenging effect of captopril and enalapril was investigated using additional pretreatments of diethyldithiocarbamate (DETCA, 0.5 mM), an inhibitor of Cu/Zn superoxide dismutase, and 3-amino-1,2,4-triazole (3AT, 50 mM), an inhibitor of catalase. Results: Both captopril and enalapril preserved vascular endothelium-dependent relaxation after exposure to ROS in a dose-dependent manner (p<0.0001). Pretreatment with DETCA attenuated the antioxidant effect of captopril and enalapril (p<0.0001), but pretreatment with 3AT did not have an effect. Conclusion: Both captopril and enalapril protect endothelium against ROS in a dose-dependent fashion in isolated rabbit abdominal aortas. This protective effect is related to superoxide anion scavenging.

• The Korean Journal of Physiology and Pharmacology
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• 제10권2호
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• pp.85-94
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• 2006

A splanchic artery occlusion for 90 min followed by reperfusion of the mesenteric circulation resulted in a severe form of circulatory shock, characterized by endothelial dysfunction, severe hypotension, marked intestinal tissue injury, and a high mortality rate. The effect of defibrotide, a complex of single-stranded polydeoxyribonucleotides having antithrombotic effect, was investigated in a model of splanchnic artery occlusion (SAO) shock in urethane anesthetized rats. Occlusion of the superior mesenteric artery for 90 min produced a severe shock state, resulting in a fatal outcome within 120 min of reperfusion in many rats. Defibrotide (10 mg/kg body weight) 10 min prior to reperfusion significantly improved mean arterial blood pressure in comparison to vehicle treated rats (p＜0.05). Defibrotide treatment also significantly attenuated in the increase of plasma amino nitrogen concentration, intestinal myeloperoxidase activity, intestinal lipid peroxidation, infiltration of neutrophils in intestine and thrombin induced adherence of neutrophils to superior mesentric artery segments. Superoxide anion and hydrogen peroxide production in $1{\mu}M$ formylmethionylleucylphenylalanine (fMLP)-activated PMNs was inhibited by defibrotide in a dose-dependent fashion. Defibrotide effectively scavenged hydrogen peroxide, but not hydroxyl radical. Treatment of SAO rats with defibrotide inhibited tumor necrosis factor-${\alpha}$, and interleukin-1${\beta}$ productions in blood in comparison with untreated rats. These results suggest that defibrotide partly provides beneficial effects by preserving endothelial function, attenuating neutrophil accumulation, and antioxidant in the ischemic reperfused splanchnic circulation

• Toxicological Research
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• 제30권3호
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• pp.149-157
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• 2014

Smoking is one of the most serious but preventable causes of cardiovascular disease (CVD). Key aspects of pathological process associated with smoking include endothelial dysfunction, a prothrombotic state, inflammation, altered lipid metabolism, and hypoxia. Multiple molecular events are involved in smoking-induced CVD. However, the dysregulations of reactive oxygen species (ROS) generation and metabolism mainly contribute to the development of diverse CVDs, and NADPH oxidase (NOX) has been established as a source of ROS responsible for the pathogenesis of CVD. NOX activation and resultant ROS production by cigarette smoke (CS) treatment have been widely observed in isolated blood vessels and cultured vascular cells, including endothelial and smooth muscle cells. NOX-mediated oxidative stress has also been demonstrated in animal studies. Of the various NOX isoforms, NOX2 has been reported to mediate ROS generation by CS, but other isoforms were not tested thoroughly. Of the many CS constituents, nicotine, methyl vinyl ketone, and ${\alpha}$,${\beta}$-unsaturated aldehydes, such as, acrolein and crotonaldehyde, appear to be primarily responsible for NOX-mediated cytotoxicity, but additional validation will be needed. Human epidemiological studies have reported relationships between polymorphisms in the CYBA gene encoding p22phox, a catalytic subunit of NOX and susceptibility to smoking-related CVDs. In particular, G allele carriers of A640G and $-930^{A/G}$ polymorphisms were found to be vulnerable to smoking-induced cardiovascular toxicity, but results for C242T studies are conflicting. On the whole, evidence implicates the etiological role of NOX in smoking-induced CVD, but the clinical relevance of NOX activation by smoking and its contribution to CVD require further validation in human studies. A detailed understanding of the role of NOX would be helpful to assess the risk of smoking to human health, to define high-risk subgroups, and to develop strategies to prevent or treat smoking-induced CVD.

• Biomolecules & Therapeutics
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• 제28권5호
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• pp.423-430
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• 2020

Telmisartan is an angiotensin-II receptor blocker and acts as a selective modulator of peroxisome proliferator-activated receptor gamma (PPARγ). Several studies have demonstrated that telmisartan ameliorates depression and memory dysfunction and reduces brain inflammation. We hypothesized that the beneficial effects of telmisartan on brain could be due to modulation of the blood-brain barrier (BBB) function. Here, we examined the effect of telmisartan on tumor necrosis factor alpha (TNF-α)-induced expression of intercellular adhesion molecule 1 (ICAM-1) which plays an important role in leukocyte transcytosis through the BBB. Telmisartan blocked TNF-α-induced ICAM-1 expression and leukocyte adhesion in U87MG human glioma cells but showed no effect on human brain microvascular endothelial cells. In U87MG cells, a PPAR antagonist, GW9662 did not block the effect of telmisartan on ICAM1 expression but rather potentiated. Moreover, GW9662 caused no change in TNF-α-induced ICAM-1 expression, suggesting no implication of PPARγ in the telmisartan effect. Further studies showed that telmisartan blocked TNF-α-induced activation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and nuclear factorkappa B (NF-κB). In contrast, inhibitors of JNK, ERK1/2 and NF-κB but not p38, blocked ICAM-1 expression induced by TNF-α. Thus, our findings suggest that the beneficial effect of telmisartan is likely due to the reduction of astrocytic ICAM1 expression and leukocytes adhesion to astrocytes, and that this response was mediated by the inhibition of JNK/ERK1/2/NF-κB activation and in the PPAR-independent manner. In conclusion, this study enhances our understanding of the mechanism by which telmisartan exerts the beneficial brain function.

• The Korean Journal of Physiology and Pharmacology
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• 제25권4호
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• pp.281-296
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• 2021

The beneficial effects of hypoxic preconditioning are abolished in the diabetes. The present study was designed to investigate the protective effects and mechanisms of repeated episodes of whole body hypoxic preconditioning (WBHP) in db/db mice. The protective effects of preconditioning were explored on diabetes-induced vascular dysfunction, cognitive impairment and ischemia-reperfusion (IR)-induced increase in myocardial injury. Sixteen-week old db/db (diabetic) and C57BL/6 (non-diabetic) mice were employed. There was a significant impairment in cognitive function (Morris Water Maze test), endothelial function (acetylcholine-induced relaxation in aortic rings) and a significant increase in IR-induced heart injury (Langendorff apparatus) in db/db mice. WBHP stimulus was given by exposing mice to four alternate cycles of low (8%) and normal air O₂ for 10 min each. A single episode of WBHP failed to produce protection; however, two and three episodes of WBHP significantly produced beneficial effects on the heart, brain and blood vessels. There was a significant increase in the levels of brain-derived neurotrophic factor (BDNF) and nitric oxide (NO) in response to 3 episodes of WBHP. Moreover, pretreatment with the BDNF receptor, TrkB antagonist (ANA-12) and NO synthase inhibitor (L-NAME) attenuated the protective effects imparted by three episodes of WBHP. These pharmacological agents abolished WBHP-induced restoration of p-GSK-3β/GSK-3β ratio and Nrf2 levels in IR-subjected hearts. It is concluded that repeated episodes of WHBP attenuate cognitive impairment, vascular dysfunction and enhancement in IR-induced myocardial injury in diabetic mice be due to increase in NO and BDNF levels that may eventually activate GSK-3β and Nrf2 signaling pathway to confer protection.

• Clinical and Experimental Pediatrics
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• 제46권1호
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• pp.56-66
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• 2003

목 적 : 제대정맥은 모체의 혈액을 태아로 운반하여 산소와 영양물질을 공급하는 유일한 통로이다. 이러한 제대 혈류의 장애가 있을 시 자궁내 성장제한, 임신성 고혈압 등을 초래할 수 있다. 제대-태반 혈관의 내피세포 손상을 유발하는 원인 중 amiloride 유도체들을 중심으로 내피세포에 미치는 amiloride 유도체들의 작용을 밝히고, 세포 내 이온농도 변화와 apoptosis 간의 관계를 규명하고자 하였다. 방 법 : 인간 제대정맥 내피세포는 Clonetics로부터 구입하였으며, 내피세포 성장에 필요한 여러 성장인자가 포함된 배지에서 배양하였다. MTT 방법과 flow cytometry 방법을 이용하여 세포독성 효과 및 apoptosis를 확인하였다. 세포 내 이온농도 변화를 측정하기 위해서는 각각의 목적에 적합한 형광염료들을 세포 내에 부하시켜 놓은 뒤, 형광 현미경과 연결된 영상분석장치를 이용하여 관찰하였다. 결 과 : 1) Amiloride 유도체들은 농도 의존적으로 HUVEC의 사멸을 나타내었으며, 각각의 정도는 HMA($IC_{50}$; $11.2{\mu}M$), MIA($13.6{\mu}M$)>EIPA($30.8{\mu}M$)>>amiloride($106{\mu}M$) 순이었다. 2) 세포주기 분석결과 apoptosis의 특징적인 sub $G_0/G_1$ ploidy peak를 나타냈으며, 이러한 작용은 caspase 억제제에 의해 감소되었다. 3) Annexin-V와 propidium iodide 이중 염색 결과 apoptosis로 진행된 세포의 비율(73.0%)을 대조군(11.3%)에 비해 현저히 증가시켰다. 4) HMA에 의한 apoptosis 효과는 세포외액의 pH를 높이거나, $NH_4Cl$을 투여하여 세포내액의 pH를 높일 경우 크게 증가하였다. 5) HMA는 농도 의존적으로 세포내 주요 이온인 $K^+$ 및 $Cl^-$의 세포내 농도를 감소시켰으며, 이러한 효과 역시 세포외액의 pH를 높일수록 현저하게 증가하였다. 결 론 : 이상의 결과들로 미루어 볼 때, HUVEC에서 amiloride 유도체들에 의한 apoptosis 과정에 세포내 주요 이온 농도 감소가 일부 관여하고 있을 것이라 생각된다.

• Journal of Chest Surgery
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• 제32권2호
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• pp.138-143
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• 1999

배경: 혈관 내피층에서 분비되어 평활근층 이완을 일으키는 물질의 본체는 산화질소(nitric oxide, NO)이며 NO synthase(NOS)에는 뇌형(brain NOS, bNOS), 내피세포형(endothelial constitutive NOS, ecNOS) 및 유도형 (inducible NOS, iNOS) 등 세 가지 동위효소가 있음이 알려져 있다. 고혈압은 혈관 내피층 기능 이상을 보임이 알려져 있으나 NOS 동위 효소의 변화를 포함한 세포내 기전은 아직 확실치 않다. 저자들은 고혈압 기전을 구명하기 위한 일환으로 고혈압 혈관에서 NOS 동위효소가 어떻게 변화되는가 조사하고자 하였다. 대상 및 방법: 흰쥐에서 two-kidney, one clip (2K1C) 고혈압과 deoxycorticosterone acetate(DOCA)-salt 고혈압을 일으켰다. 4주 뒤 고혈압이 일어난 것을 확인하고 적출 흉부 대동맥 표본에서 Western blot 분석에 의한 NOS 동위효소 발현 조사 및 비색법에 의한 조직내 산화질소 정량을 하였다. 결과: 2K1C 및 DOCA-salt 흰쥐에서 실험군은 각각의 대조군에 비해 유의하게 높은 혈압을 보였다. 두 고혈압군에서 모두 적출 대동맥 표본의 bNOS 및 ecNOS 단백 발현이 감소되었다. iNOS 단백은 DOCA-salt 고혈압에서 변화를 보이지 않으나 2K1C 고혈압에서는 역시 감소를 보였다. 혈관조직내 산화질소 함량은 두 고혈압에서 모두 유의하게 감소되었다. 결론: 2K1C 및 DOCA-salt 고혈압에서 혈관의 NOS 발현과 산화질소 함량이 감소되어 있으며 이는 고혈압의 유지 기전에 공헌하리라 추측되었다.