Delayed arterial healing at culprit sites after drug-eluting stent (DES) placement for acute myocardial infarction (AMI) is associated with increased risk of late stent thrombosis. The Korea Acute Myocardial Infarction Registry was established in commemoration of the 50(th) anniversary of Korea Circulation Society. Between November 2005 and December 2016, more than 62,000 patients were registered from 50 primary percutaneous coronary intervention (PCI) centers in Korea. DES in AMI may be safe and effective, however, there is concern about increased stent thrombosis after DES implantation in AMI patients, requiring longer-term dual anti-platelet therapy to reduce the risk of late stent thrombosis. Device innovation is needed to overcome issues such as stent thrombosis and restenosis by using new coating materials with biocompatible polymers, different coating methods using non-polymer techniques, bioabsorbable stents and pro-healing stents. In this review article, we describe the current usage of DES in AMI in Korea and introduce novel DES uses in development for patients with AMI. We have developed many types of DES in our research laboratory. Abciximab-coated stents inhibited platelet thrombi and restenosis. Furthermore, anti-oxidants (carvedilol, probucol and alpha-lipoic acid) were used for stent coating. Currently we are developing novel DESs using polymer-free and natural binding techniques, peptide coating stents, gene-and-drug delivery, bioabsorbable stents using 3D printing, endothelial progenitor cell capturing stents to promote reendothelialization and reduce stent thrombosis. New DESs in development may be safe and effective in preventing late stent thrombosis and restenosis in patients with AMI.
Anniversaries and Special Events ; Blood Platelets ; Drug-Eluting Stents ; Endothelial Progenitor Cells ; Humans ; Korea ; Myocardial Infarction ; Percutaneous Coronary Intervention ; Polymers ; Printing, Three-Dimensional ; Probucol ; Stents ; Thrombosis

OBJECTIVETo determine the effects of probucol on serum parameters and liver histopathology in rats with non-alcoholic steatohepatitis (NASH) and explore the mechanisms.

METHODSForty male Sprague-Dawley rats were randomly assigned into 4 equal groups, namely the normal control group (NC group) with a standard feeding, high-fat diet group (HD group) fed with a high-fat diet, probucol (500 mg/kg daily) control group (NP group) fed with standard diet, and probucol group fed with a high-fat diet (HP group). After 15 weeks of feeding, the rats were euthanized for histopathological inspection of the liver with HE staining and detection of farnesoid X receptor (FXR), SHP and SREBP-1C expressions using semi-quantitative RT-PCR and Western blotting.

RESULTSAfter the 15-week feeding, the rats in HP group had significantly lower levels of serum ALT, AST, cholesterol, bile acid, and free fatty acid than those in HD group (P<0.01 or 0.05). Compared with the normal control group, high-fat diet feeding resulted in significantly decreased mRNA and protein levels of FXR and SHP (P<0.05) and significantly increased SREBP-1C level (P<0.05). These high-fat diet-induced gene expression changes were reversed by probucol intervention (P<0.05).

CONCLUSIONProbucol treatment has beneficial effects on serum parameters, hepatic steatosis, and lobular inflammation in high-fat diet-induced NASH possibly by up-regulating FXR expression.

Animals ; Anticholesteremic Agents ; pharmacology ; Diet, High-Fat ; Disease Models, Animal ; Male ; Non-alcoholic Fatty Liver Disease ; blood ; drug therapy ; Probucol ; pharmacology ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To observe the therapeutic effect of probucol on serum malondialdehyde (MDA) and superoxide dismutase (SOD) in patients with primary hypertension. METHODS: A randomized study was performed on 40 patients with hypertension. The patients were randomly assigned to the control (levamlodipine besylate 2.5 mg/d plus benazepril 10 mg/d, n=20) or probucol group (levamlodipine besylate 2.5 mg/d plus benazepril 10 mg/d plus probucol 500 mg/d, n=20). An additional twenty healthy people were enrolled in the study (normal group). All subjects were followed up for a period of four weeks. Lipids and hepatic/renal function were measured at baseline and after 4 weeks. The levels of serum MDA and SOD activity were assayed by chemical colorimetry, and other indices, including blood pressure, lipids and hepatic/renal function, were measured at baseline and after 4 weeks. RESULTS: Compared to the normal group, the levels of MDA in all of the hypertension patient groups were higher, SOD was lower. The antihypertensive treatment decreased serum MDA levels but increased SOD content, and probucol treatment exaggerated these effects, with greater reduction of serum MDA levels and greater increase of SOD content. CONCLUSION The treatment with probucol can improve oxidative stress in hypertension patients, resulting in reduced serum MDA levels and improved SOD activity, thus contributing agreater antihypertensive effect.
Adult ; Antioxidants ; therapeutic use ; Female ; Humans ; Hypertension ; drug therapy ; physiopathology ; Male ; Malondialdehyde ; blood ; Middle Aged ; Oxidative Stress ; drug effects ; Probucol ; therapeutic use ; Superoxide Dismutase ; blood

PURPOSE: Puromycin aminonucleoside (PAN) specifically injures podocytes, leading to foot process effacement, actin cytoskeleton disorganization, and abnormal distribution of slit diaphragm proteins. p130Cas is a docking protein connecting F-actin fibers to the glomerular basement membrane (GBM) and adapter proteins in glomerular epithelial cells (GEpCs; podocytes). We investigated the changes in the p130Cas expression level in the PAN-induced pathological changes of podocytes in vitro. METHODS: We observed changes in the p130Cas expression in cultured rat GEpCs and mouse podocytes treated with various concentrations of PAN and antioxidants, including probucol, epigallocatechin gallate (EGCG), and vitamin C. The changes in the p130Cas expression level were analyzed using confocal immunofluorescence imaging, Western blotting, and polymerase chain reaction. RESULTS: In the immunofluorescence study, p130Cas showed a diffuse cytoplasmic distribution with accumulation at distinct sites visible as short stripes and colocalized with P-cadherin. The fluorescences of the p130Cas protein were internalized and became granular by PAN administration in a dose-dependent manner, which had been restored by antioxidants, EGCG and vitamin C. PAN also decreased the protein and mRNA expression levels of p130Cas at high doses and in a longer exposed duration, which had been also reversed by antioxidants. CONCLUSION: These findings suggest that PAN modulates the quantitative and distributional changes of podocyte p130Cas through oxidative stress resulting in podocyte dysfunction.
Actin Cytoskeleton ; Actins ; Animals ; Antioxidants ; Ascorbic Acid ; Blotting, Western ; Cadherins ; Catechin ; Crk-Associated Substrate Protein ; Cytoplasm ; Cytoskeleton ; Diaphragm ; Epithelial Cells ; Fluorescent Antibody Technique ; Foot ; Glomerular Basement Membrane ; Mice ; Oxidative Stress ; Podocytes ; Probucol ; Proteins ; Puromycin ; Puromycin Aminonucleoside ; Rats ; RNA, Messenger

BACKGROUNDThe plasma cystatin C concentration (PcyC) has been demonstrated to have prognostic value in acute coronary syndrome, but the study of PcyC in patients with borderline coronary lesions is limited. Moreover, the effects of atorvastatin and probucol on PcyC and the severity of coronary lesions are unknown. This study was to evaluate the effects of the combination of atorvastatin and probucol on PcyC and severity of coronary lesion in patients with borderline coronary lesions.

METHODSOne hundred and thirty consecutive patients with borderline coronary lesions (40% to 60% isolated single stenosis assessed by quantitative coronary angiography) were enrolled into the borderline coronary lesion (BCL) group, and one hundred and thirty-six subjects without coronary lesions comprised the controls (CTR). The subjects in the BCL group were randomized into routine treatment (RTT, n = 60), and combined treatment with atorvastatin 20 mg plus probucol 1.0 g daily added to routine medication (CBT, n = 70), both groups were treated for 6 months continuously. The levels of PcyC, high-sensitive C-reactive protein (hs-CRP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were determined. One hundred and four subjects in the BCL group were rechecked by coronary angiography.

RESULTSPcyC levels were significantly higher in the BCL group than in the CTR group; (2003.26 ± 825.73) ng/ml vs. (1897.83 ± 664.46) ng/ml (P < 0.01). Compared with patients in the RTT group, the levels of PcyC, TC, LDL-C, TG and hs-CRP were significantly lower in the CBT group (P < 0.05). Moreover, there was a trend towards a slight decrease in the RTT patients, (54.38 ± 10.67)% vs. (50.29 ± 9.89)% (P > 0.05), and a significant decrease in the CBT patients, (53.65 ± 9.48%) vs. (40.38 ± 12.93)% (P < 0.05), in the mean percent stenosis of borderline coronary lesions before and after six months of treatment.

CONCLUSIONSCystatin C played an important role in the development of coronary artery disease, and was associated with the severity of coronary lesions. The combination of atorvastatin and probucol decreased PcyC levels, and could be the treatment of choice.

Aged ; Anticholesteremic Agents ; therapeutic use ; Atorvastatin Calcium ; Coronary Disease ; blood ; drug therapy ; pathology ; Cystatin C ; blood ; Female ; Heptanoic Acids ; therapeutic use ; Humans ; Male ; Middle Aged ; Probucol ; therapeutic use ; Prospective Studies ; Pyrroles ; therapeutic use

BACKGROUNDProbucol is known to reduce the development of atherosclerotic lesions, but its impact on vascular remodeling associated with de novo atherosclerosis is incompletely understood. We therefore examined the effect of probucol on vascular remodeling in a rabbit model of established atherosclerosis.

METHODSAortic atherosclerosis was induced by a combination of endothelial injury and 10 weeks' atherogenic diet. Animals were then randomized to receive the foregoing diet without or with 1% (wt/wt) probucol for 16 weeks. At the end of week 26, in vivo intravascular ultrasound, pathological, immunohistochemical and gene expression studies were performed.

RESULTSProbucol significantly decreased vessel cross-sectional area, plaque area and plaque burden without effect on lumen area. More negative remodeling and less positive remodeling occurred in the abdominal aortas of probucol group than the control group (56% vs. 21%, 18% vs. 54%, respectively, both P < 0.01). In addition, the probucol group showed a smaller mean remodeling index relative to the control group (0.93 ± 0.13 vs. 1.05 ± 0.16, P < 0.01). Furthermore, probucol treatment decreased macrophage infiltration, inhibited apoptosis of cells within plaques, and reduced the production of matrix metalloproteinases-2, -9, cathepsin K and cathepsin S (all P < 0.01).

CONCLUSIONSThese findings suggest that probucol may attenuate the enlargement of atherosclerotic vessel walls and be associated with a negative remodeling pattern without affecting the lumen size. This effect may involve inhibition of extracellular matrix degradation and prevention of apoptosis in atherosclerotic plaques.

Animals ; Anticholesteremic Agents ; pharmacology ; Aorta ; pathology ; Apoptosis ; drug effects ; Atherosclerosis ; drug therapy ; metabolism ; pathology ; Lipids ; blood ; Macrophages ; drug effects ; physiology ; Male ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Oxidative Stress ; Probucol ; pharmacology ; Rabbits ; Ultrasonography, Interventional ; methods

OBJECTIVETo observe the effects of combination of Lumbrukinase Capsule (LC) and Probucol Tablet (PT) in treating cerebral infarction (CI) patients' unstable atheromatous plaque of the carotid artery.

METHODS150 patients were randomly assigned to the PT group and the LC group, 75 cases in each. Patients in the PT group took 0.5 g PT each time, twice daily. On the basis of PT, patients in the LC group also took 600 thousand U LC, thrice daily. The treatment course was 12 months for all. The serum levels of TC, TG, HDL-C, LDL-C, fibrinogen (FIB), and changes of the carotid atherosclerotic plaque were measured before treatment, 6 and 12 months after treatment. Meanwhile, adverse events were recorded.

RESULTSThe serum levels of TC, TG, and LDL-C were all lower 6 months after treatment than before treatment in the two groups, showing statistical significance (P < 0.05). The serum level of HDL-C was higher 6 months after treatment than before treatment in the two groups, showing no statistical significance (P > 0.05). When compared with before treatment in the same group, the serum level of FIB significantly decreased after treatment. Besides, there was statistical difference between the two groups (P < 0.05). There was no statistical difference in the serum levels of blood lipids or FIB between 12-month treatment and 6-month treatment in the same group (P > 0.05). The plaque effective rate in the LC group was superior to that of the PT group, showing statistical significance (P < 0.01). During the treatment period, the occurrence of cerebrovascular event was lower in the LC group than in the PT group (P < 0.05). Partial patients in the two groups had gastric discomfort.

CONCLUSIONSThe combination of LC and PT could prevent and treat arteriosclerosis, stabilize the plaque, effectively lower the occurrence of ischemic events. Its clinical application did not increase the risk of hemorrhage. It was safe and effective, worthy of spreading. It was necessary to further observe whether combination of LC and PT could increase side effects of the digestive tract.

Adult ; Aged ; Animals ; Biological Products ; therapeutic use ; Carotid Artery Diseases ; drug therapy ; Cerebral Infarction ; drug therapy ; pathology ; Female ; Humans ; Male ; Materia Medica ; therapeutic use ; Middle Aged ; Oligochaeta ; enzymology ; Plaque, Atherosclerotic ; drug therapy ; Probucol ; therapeutic use ; Serine Endopeptidases ; therapeutic use ; Treatment Outcome

BACKGROUNDWe hypothesize that increased atrial oxidative stress and inflammation may play an important role in atrial nerve sprouting and heterogeneous sympathetic hyperinnervation during atrial fibrillation (AF). To test the hypothesis, we examined whether the antioxidant and anti-inflammatory treatment with probucol attenuates atrial autonomic remodeling in a canine model of AF produced by prolonged rapid right atrial pacing.

METHODSTwenty-one dogs were divided into a sham-operated group, a control group and a probucol group. Dogs in the control group and probucol group underwent right atrial pacing at 400 beats per minute for 6 weeks, and those in the probucol group received probucol 1 week before rapid atrial pacing until pacing stopped. After 6-week rapid atrial pacing, general properties including left atrial structure and function, atrial hemodynamics and the inducibility and duration of AF were measured in all the groups. Atrial oxidative stress markers and serum C-reactive protein (CRP) concentration were estimated. The degree of nerve sprouting and sympathetic innervation at the right atrial anterior wall (RAAW) and the left atrial anterior wall (LAAW) were quantified by immunohistochemistry, atrial norepinephrine contents were also detected. Atrial beta-nerve growth factor (beta-NGF) mRNA and protein expression at the RAAW and LAAW were assessed by real-time quantitative RT-PCR and Western blotting respectively.

RESULTSAtrial tachypacing induced significant nerve sprouting and heterogeneous sympathetic hyperinnervation, and the magnitude of nerve sprouting and hyperinnervation was higher in the RAAW than in the LAAW. Atrial beta-NGF mRNA and protein levels were significantly increased at the RAAW and LAAW, and the upregulation of beta-NGF expression was greater at the RAAW than at the LAAW in the control group. The beta-NGF protein level was positively correlated with the density of sympathetic nerves in all groups. Probucol decreased the increase of CRP concentration and attenuated atrial oxidative stress caused by atrial tachypacing. In addition, probucol could effectively inhibit atrial beta-NGF upregulation, significantly attenuate atrial nerve sprouting and heterogeneous sympathetic hyperinnervation, and dramatically reduce the inducibility and duration of AF.

CONCLUSIONSThe atrial over-expression of beta-NGF possibly caused by increased oxidative stress and inflammation may be the main mechanism underlying atrial autonomic remodeling during AF. Probucol attenuates atrial autonomic remodeling possibly by its antioxidant and anti-inflammatory actions.

Animals ; Antioxidants ; therapeutic use ; Atrial Fibrillation ; drug therapy ; Blotting, Western ; C-Reactive Protein ; metabolism ; Cardiac Pacing, Artificial ; adverse effects ; Disease Models, Animal ; Dogs ; Electrocardiography ; Female ; Heart Atria ; Immunohistochemistry ; Male ; Nerve Growth Factor ; genetics ; metabolism ; Norepinephrine ; metabolism ; Probucol ; therapeutic use ; Reverse Transcriptase Polymerase Chain Reaction

In the present study, we aimed to identify the synergistic effects of concurrent treatment of low concentrations of cilostazol and probucol to inhibit the oxidative stress with suppression of inflammatory markers in the cultured human coronary artery endothelial cells (HCAECs). Combination of cilostazol (0.3~3micrometer) with probucol (0.03~0.3micrometer) significantly suppressed TNF-alpha-stimulated NAD(P)H-dependent superoxide, lipopolysaccharide (LPS)-induced intracellular reactive oxygen species (ROS) production and TNF-alpha release in comparison with probucol or cilostazol alone. The combination of cilostazol (0.3~3micrometer) with probucol (0.1~0.3micrometer) inhibited the expression of vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) more significantly than did the monotherapy with either probucol or cilostazol. In line with these results, combination therapy significantly suppressed monocyte adhesion to endothelial cells. Taken together, it is suggested that the synergistic effectiveness of the combination therapy with cilostazol and probucol may provide a beneficial therapeutic window in preventing atherosclerosis and protecting from cerebral ischemic injury.
Atherosclerosis ; Chemokine CCL2 ; Coronary Vessels ; Endothelial Cells ; Humans ; Monocytes ; Oxidative Stress ; Probucol ; Reactive Oxygen Species ; Superoxides ; Tetrazoles ; Tumor Necrosis Factor-alpha ; Vascular Cell Adhesion Molecule-1

Heme oxygenase-1 (HO-1) is a cellular stress protein, and its expression plays an important regulatory role in a lot of physiological and pathological processes. Although the expression of HO-1 in most tissues of body is low, a number of clinical and pharmacological experiments have proved that many compounds can induce HO-1 expression. The increase of HO-1 expression is the result of regulating different signaling pathways and transcription factors, and this induction of HO-1 is suggested to be partially therapeutic efficacy of these compounds. This article summarizes some kinds of compounds in this field of research at home and abroad over the last 10 years, and provides a brief analysis of the mechanism.
Animals ; Antineoplastic Agents ; pharmacology ; Antioxidants ; pharmacology ; Coumarins ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Enzyme Induction ; drug effects ; Gene Expression Regulation, Enzymologic ; Heme Oxygenase-1 ; genetics ; metabolism ; Humans ; Lovastatin ; pharmacology ; Nitric Oxide ; pharmacology ; Peptide Hormones ; pharmacology ; Probucol ; pharmacology ; Signal Transduction ; Transcription Factors ; metabolism