• Title/Summary/Keyword: endothelium function

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Ref-1 protects against FeCl3-induced thrombosis and tissue factor expression via the GSK3β-NF-κB pathway

  • Lee, Ikjun;Nagar, Harsha;Kim, Seonhee;Choi, Su-jeong;Piao, Shuyu;Ahn, Moonsang;Jeon, Byeong Hwa;Oh, Sang-Ha;Kang, Shin Kwang;Kim, Cuk-Seong
    • The Korean Journal of Physiology and Pharmacology
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    • v.25 no.1
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    • pp.59-68
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    • 2021
  • Arterial thrombosis and its associated diseases are considered to constitute a major healthcare problem. Arterial thrombosis, defined as blood clot formation in an artery that interrupts blood circulation, is associated with many cardiovascular diseases. Oxidative stress is one of many important factors that aggravates the pathophysiological process of arterial thrombosis. Apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ref-1) has a multifunctional role in cells that includes the regulation of oxidative stress and anti-inflammatory function. The aim of this study was to investigate the therapeutic effect of adenovirus-mediated Ref-1 overexpression on arterial thrombosis induced by 60% FeCl3 solution in rats. Blood flow was measured to detect the time to occlusion, thrombus formation was detected by hematoxylin and eosin staining, reactive oxygen species (ROS) levels were detected by high-performance liquid chromatography, and the expression of tissue factor and other proteins was detected by Western blot. FeCl3 aggravated thrombus formation in carotid arteries and reduced the time to artery occlusion. Ref-1 significantly delayed arterial obstruction via the inhibition of thrombus formation, especially by downregulating tissue factor expression through the Akt-GSK3β-NF-κB signaling pathway. Ref1 also reduced the expression of vascular inflammation markers ICAM-1 and VCAM-1, and reduced the level of ROS that contributed to thrombus formation. The results showed that adenovirus-mediated Ref-1 overexpression reduced thrombus formation in the rat carotid artery. In summary, Ref-1 overexpression had anti-thrombotic effects in a carotid artery thrombosis model and could be a target for the treatment of arterial thrombosis.

Effect of Geijibokryunghwan and each constituent herb on inhibition of platelet aggregation (계지복령환(桂枝茯笭丸) 및 그 구성약물(構成藥物)의 혈소판응집억제(血小板凝集抑制)에 관(關)한 연구(硏究))

  • Kim, Jong-Goo;Park, Sun-Dong;Park, Won-Hwan
    • The Journal of Dong Guk Oriental Medicine
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    • v.8 no.2
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    • pp.115-129
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    • 2000
  • The cause that the increase of animality fat intakes, under exercise, fatness, adding the stress, advanced age etc., the occurrence rate of the circulation system disease has been increased. And the thrombosis importantly came to the front as the risk factor of these circulation system's disease. Nowadays, the ischemic disease has especially discussed, for example the angina or myocardial infarction, originated in thrombosis that came from the platelet aggregation. In the western medicine, as the cure and prevention, using the aspirin or ticlopidine for platelet aggregation suppressant. But in the , the curing method must be used properly according to the pectoralgia or heartache's kind, state, grade. The platelet do not attache to the normal hemangioendothelial cell. But when it stimulated by endothelium peronia and so on, it attache to the injury endothelium or rise aggregation between the platelet. On this time, it secrete the platelet aggregation inducer as like ADP, thromboxane A2 from the inside of platelet. So it has first defensive function through the aggregation augment that prevent the celerity consumption of blood. But the activation of abnormal platelet occur the platelet grume and thrombogenesis. So it bring up the occlusive angiosis, so to speak, cardiovascular disease, cerebrovascular disease, arterial sclerosis. In oriental medicine, the thrombosis in the category of blood stasis and this blood stasis present the generalise or local blood circulation disturbance that generated by all kinds of pathological fact or blood stream retention accompanying with a series of syndrome. As the syndrome, stabbing pain fixed at certain region, squamous and dry skin, fullness and pain of the chest and hypochondrium, firmness and fullness of the lower abdomen, black stool, dark purple tongue or with ecchymoses and petechiae etc.. has been created. And it becomes the pathopoiesis cause that the convulsion and palpitation, severe palpitatiion, tympanites, the symtom complex with a mass or swelling in the abdomen, insanity, stricken by wind etc.. Moreover, it used the drugs for invigorating blood circulation and eliminating blood stasis or drugs for removing blood stasis for all kinds of syndrome through the blood stasis. And the drugs for activating the blood circulation, such as Salviae Radix, Angelicae Sinensis Radix, Persicae Semen, Achyranthis Radix, Cnidii Rhizoma, Carthami Flos are used for that. And it is used to the herbs of insects that has strong effect about the disintergrating blood stasis such as Hirudo, Scolopendrae Corpus, Buthus, Lumbricus etc.. On this study, It used Geijibokryunghwan(GBH) and the consisting herbs to investigate the influence of platelet aggregation about drugs that used to improvement various symptoms created by the thrombosis in oriental medicine. GBH formula has as formula recorded in the , action of 'eleminating the evil and not impairment of healthy energy' and 'promoting the flow of QI and cold and heat, so used for the expel blood stasis herbs from the ancient. Therefore we investigated the restraint effect of GBH and the consisting herbs about the platelet agregation induced to the ADP, AA or collagen. The conclusion is following. 1. When it added the aggregation inducer after that it added GBH and individual consisting herbs in the PRP, GBH showed the (+) inhibition effect on the platelet aggregation and it showed the (+) inhibition effect in the individual consisting herbs as like Paeoniae Radix and Moutan Cortex Radicis. 2. It showed the (+), (+,++) inhibition effect on the platelet aggregation in Paeoniae Radix Hoelen, Paeoniae Radix Moutan Cortex Radicis, Hoelen Moutan Cortex Radicis etc. 3. In the aggregation inhibition activating on the difference of density, GBH showed strong inhibition effect to the aggregation state induced to collagen, and it showed the inhibition effect in the individual consisting herbs as like Paeoniae Radix and Moutan Cortex Radicis about the aggregation induced by the collagen. 4. It showed the strong inhibition effect about the aggregation induced by the collagen in Paeoniae Radix Hoelen, Paeoniae Radix Moutan Cortex Radicis, Hoelen Moutan Cortex Radicis etc Like this, as confirm GBH and the individual consisting herb's inhibition effect of platelet aggregation, We considerated that GBH and the individual consisting herbs have practical applicational value of clinical trial in the thrombosis caused by platelet aggregation.

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Effect of Platelet Activation on Pulmonary Hypertension in Chronic Obstructive Pulmonary Diseases (만성폐쇄성폐질환에서 혈소판 활성도가 폐동맥 고혈압에 미치는 영향)

  • Kim, Hyung-Jung;Nam, Moon-Suk;Kwon, Hyuck-Moon;Ahn, Chul-Min;Kim, Sung-Kyu;Lee, Won-Young;Song, Kyung-Soon
    • Tuberculosis and Respiratory Diseases
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    • v.40 no.2
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    • pp.147-152
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    • 1993
  • Background: There is evidence that platelet is activated in chronic obstructive pulmonary disease and activated platelet with injured endothelium contribute to the pathogenesis of pulmonary hypertension, prognostic factor of chronic obstructive pulmonary disease. So, we have investigated platelet function further in chronic obstructive pulmonary disease and effect of platelet activation on pulmonary hypertension. Method: We studied platelet aggregation ratio and alpha-granule products such as platelet factor 4(PF4) and beta-thromboglobulin (${\beta}$-TG) in control subjects and COPD without and with pulmonary hypertension subjects. Result: 1) The platelet aggregation ratio (PAR) was $0.99{\pm}0.04$ in control subjects, $0.98{\pm}0.05$ in COPD without pulmonary hypertension subjects and $0.89{\pm}0.08$ in COPD with pulmonary hypertension subjects. The platelet aggregation ratio of COPD subjects was tend to decrease than that of control subjects and the ratio of COPD with pulmonary hypertension subjects was significantly lower than that of control subjects. 2) The platelet factor 4 (PF4, IU/ml) was $4.7{\pm}1.2$ in control subjects, $18.6{\pm}4.9$ in COPD without pulmonary hypertension subjects and $57.2{\pm}12.7$ in COPD with pulmonary hypertension subjects. The level of COPD subjects was significantly higher than that of control subjects and the level of COPD with pulmonary hypertension subjects was significantly higher than that of COPD without pulmonary hypertension subjects. 3) The beta-thromboglobulin (${\beta}$-TG, IU/ml) was $34.4{\pm}5.8$ in control subjects, $80.4{\pm}18.1$ in COPD without pulmonary hypertension subjects and $93.0{\pm}14.0$ in COPD with pulmonary hypertension subjects. The level of COPD subjects was significantly higher than that of conrtrol subjects and the level of COPD with pulmonary hypertension subjects was tend to increase than that of COPD without pulmonary hypertension subjects. 4) There was no correlation between the clinical parameters and PAR, PF4 and ${\beta}$-TG but there was significant correlation among PAR, PF4 and ${\beta}$-TG. Conclusion: The platelet is activated in chronic obstructive pulmonary disease and the platelet of COPD with pulmonary hypertension is tend to be activated more than that of COPD without pulmonary hypertension. So, activated platelet may involve in the pathogenesis and maintenance of pulmonary hypertension in COPD subjects and modulation of platelet activity that might reduce pulmonary hypertension needs to be determined.

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