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Young Joon Hong,
Myung Ho Jeong, Youngkeun Ahn,
Gary S Mintz,
Sang Wook Kim,
Sung Yun Lee,
Seok Yeon Kim,
Jeong Gwan Cho,
Jong Chun Park,
Augusto D Pichard,
Lowell F Satler,
Ron Waksman,
Jung Chaee Kang,
Neil J Weissman
International journal of cardiology 04/2013; · 7.08 Impact Factor
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Young Joon Hong,
Myung Ho Jeong,
Yun Ha Choi,
Soo Young Park,
Si Hyun Rhew,
Hae Chang Jeong,
Jae Yeong Cho,
Soo Young Jang,
Ki Hong Lee,
Keun Ho Park,
Doo Sun Sim,
Nam Sik Yoon,
Hyun Ju Yoon,
Kye Hun Kim,
Hyung Wook Park,
Ju Han Kim, Youngkeun Ahn,
Jeong Gwan Cho,
Jong Chun Park,
Jung Chaee Kang
International journal of cardiology 04/2013; · 7.08 Impact Factor
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Namsik Yoon,
Jeong Gwan Cho,
Kye Hun Kim,
Keun Ho Park,
Doo Sun Sim,
Hyun Ju Yoon,
Young Joon Hong,
Hyung Wook Park,
Ju Han Kim, Youngkeun Ahn,
Myung Ho Jeong,
Jong Chun Park
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ABSTRACT: The remodeling of gap junctions may affect their conduction properties and contribute to the maintenance of atrial fibrillation. The significance of the role of angiotensin-II receptor blockers (ARBs) in upstream therapy is not clear. This study was performed to investigate the effects of ARBs on atrial remodeling in a heart failure model. A model of heart failure was established or sham surgery performed in 24 Sprague-Dawley male rats. The rats were divided into sham, heart failure and heart failure-ARB groups. In the ARB group, 30 mg/kg of losartan was administered each day for 4 weeks. Echocardiography was performed at the baseline and 4 weeks following the surgery. An atrial fibrillation induction study and histological and immunohistochemical evaluation were performed 4 weeks after surgery. The increase in the left atrial diameter of the heart failure-ARB group was smaller than that of the heart failure group (P=0.028). The atrial fibrillation inducibility and duration of induced atrial fibrillation were not different between the heart failure and heart failure-ARB groups. Masson's trichrome staining revealed less fibrosis in the heart failure-ARB group compared with the heart failure group. Immunohistochemical staining and western blot analysis for connexin 43 showed a lower expression level in the heart failure-ARB group compared with that in the heart failure group. In a rat model of ischemic heart failure the ARB losartan had structural and histological atrial reverse-remodeling effects. However, its role as an electrical stabilizer requires further study.
Experimental and therapeutic medicine 04/2013; 5(4):1009-1016.
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ABSTRACT: OBJECTIVE: Cilostazol, a selective phosphodiesterase-3 (PDE-3) inhibitor, can effectively suppress platelet activation and attenuate the increase in carotid intima-media thickness in diabetes mellitus (DM) patients. Therefore, we investigated whether cilostazol had effects on the healing process after implantation of a drug-eluting stent (DES) in a rat model of type 1 DM. METHODS AND RESULTS: Streptozotocin-induced DM rats were divided into 2 groups in which cilostazol (30 mg/kg/day; DM-Cilostazol) or vehicle (DM-Vehicle) was orally administered. Age-matched rats treated with the vehicle were used as a control group (NDM-Vehicle). After 4 weeks, cilostazol changed the expression of vascular cell adhesion molecule and intercellular adhesion molecule and the apoptotic cell ratio of the media (DM-Vehicle: 53.5 ± 9.8%, DM-Cilostazol: 26.4 ± 8.3%, p < 0.05) in the aortic wall. Also, in a modified aortic ring test, cilostazol preserved the angiogenic potential of the aorta ([height of the sprouting tubes] DM-Vehicle: 0 ± 0 μm, DM-Cilostazol: 344.6 ± 236.8 μm, p < 0.05). After implantation of paclitaxel-eluting stents (PES) in rats treated with cilostazol or vehicle, thrombus formation, deposition of fibrin, and infiltration of inflammatory cells were attenuated by cilostazol. In particular, the re-endothelialization by von Willebrand factor expression in the DM-PES-Cilostazol group was enhanced compared with that in the DM-PES-Vehicle group. CONCLUSION: Cilostazol has potential for protecting vessels against hyperglycemic injury and for accelerating the healing process after implantation of DES.
Atherosclerosis 03/2013; · 3.79 Impact Factor
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The Korean Journal of Internal Medicine 03/2013; 28(2):156-8.
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Hyun Ju Yoon,
Kye Hun Kim,
Sang Hyun Lee,
Yi Rang Yim,
Kyung Jin Lee,
Keun Ho Park,
Doo Sun Sim,
Nam Sik Yoon,
Young Joon Hong,
Hyung Wook Park,
Ju Han Kim, Youngkeun Ahn,
Myung Ho Jeong,
Jeong Gwan Cho,
Jong Chun Park
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ABSTRACT: Aortic stiffness and intima-media thickness (IMT) are known to be associated with ischemic stroke. The aim of the present study was to investigate the differences of aortic stiffness and IMT between cerebral infarction (CI) and transient ischemic attack (TIA).
A total of 500 patients with acute stroke were divided into 2 groups: the TIA group (n = 230, 62.4 ± 12 years, 144 males) versus CI group (n = 270, 63.4 ± 11 years, 181 males). Aortic stiffness index and IMT, as well as conventional cardiovascular risk factors, were compared.
The prevalence of hypertension, diabetes, and dyslipidemia were significantly higher, and left atrial volume and E/E' were significantly elevated in the CI group than in the TIA group. Carotid IMT was significantly thicker in the CI group than in the TIA group. Aortic stiffness index β was significantly higher (7.99 ± 2.70 vs. 7.02 ± 4.30, p = 0.043) and aortic IMT was significantly thicker (1.53 ± 0.41 vs. 1.45 ± 0.39 mm, p = 0.040) in the CI group than in the TIA group. Aortic stiffness index β was significantly correlated with the IMT of the aorta (r = 0.279, p = 0.014), right (r = 412, p < 0.001) and left carotid artery (r = 441, p < 0.001).
Aortic stiffness index β and IMT were significantly higher in patients with CI than TIA. The result of the present study suggested that CI is associated with more advanced degree of atherosclerotic and arteriosclerotic process than TIA.
Journal of cardiovascular ultrasound 03/2013; 21(1):12-7.
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ABSTRACT: As the first nationwide Korean prospective multicenter data collection registry, the Korea Acute Myocardial Infarction Registry (KAMIR) launched in November 2005. Through a number of innovative approaches, KAMIR suggested new horizons about acute myocardial infarction (AMI) which contains unique features of Asian patients from baseline characteristics to treatment strategy. Obesity paradox was existed in Korean AMI patients, whereas no gender differences among them. KAMIR score suggested new risk stratifying method with increased convenience and an enhanced accuracy for the prediction of adverse outcomes. Standard loading dose of clopidogrel was enough for Asian AMI patients. Triple antiplatelet therapy with aspirin, clopidogrel and cilostazol could improve clinical outcomes than dual antiplatelet therapy with aspirin and clopidogrel. Statin improved clinical outcomes even in AMI patients with very low LDL-C levels. The rate of percutaneous coronary intervention was higher and door-to-balloon time was shorter than the previous reports. Zotarolimus eluting stents as the 2nd generation drug-eluting stent (DES) was not superior to the 1st generation DES, in contrast to the western AMI studies. KAMIR made a cornerstone in the study of Korean AMI and expected to be new standards of care for AMI with the renewal of KAMIR design to overcome its pitfalls.
Journal of Korean medical science 02/2013; 28(2):173-80. · 0.84 Impact Factor
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Doo Sun Sim,
Myung Ho Jeong,
Kyung Hoon Cho, Youngkeun Ahn,
Young Jo Kim,
Shung Chull Chae,
Taek Jong Hong,
In Whan Seong,
Jei Keon Chae,
Chong Jin Kim,
Myeong Chan Cho,
Seung-Woon Rha,
Jang Ho Bae,
Ki Bae Seung,
Seung Jung Park
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ABSTRACT: The benefit of early statin treatment following acute myocardial infarction (MI) complicated with cardiogenic shock (CS) has not been well studied. We sought to assess the effect of early statin therapy in patients with CS complicating acute MI.
We studied 553 statin-naive patients with acute MI and CS (Killip class IV) who underwent revascularization therapy between November 2005 and January 2008 at 51 hospitals in the Korea Acute Myocardial Infarction Registry. Patients were divided into 2 groups: those who received statins during hospitalization (n=280) and those who did not (n=273). The influence of statin treatment on a 12-month clinical outcome was examined using a matched-pairs analysis (n=200 in each group) based on the propensity for receiving statin therapy during hospitalization.
Before adjustment, patients receiving statin, compared to those not receiving statin, had a more favorable clinical profile, were less likely to suffer procedural complications, and more likely to receive adequate medical therapy. Patients receiving statin had lower unadjusted in-hospital mortality and composite rate of mortality, MI, and repeat revascularization at 12 months, which remained significantly lower after adjustment for patient risk, procedural characteristics, and treatment propensity.
In CS patients with acute MI undergoing revascularization therapy, early statin treatment initiated during hospitalization was associated with lower rates of in-hospital death and 12-month adverse cardiac events.
Korean Circulation Journal 02/2013; 43(2):100-109.
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Hyun Ju Yoon, Youngkeun Ahn,
Kye Hun Kim,
Jong Chun Park,
Dong-Ju Choi,
Seongwoo Han,
Eun-Seok Jeon,
Myung-Chan Cho,
Jae-Joong Kim,
Byung-Su Yoo,
Mi-Seung Shin,
In-Whan Seong,
Seok-Min Kang,
Yung-Jo Kim,
Hyung Seop Kim,
Shung Chull Chae,
Byung-Hee Oh,
Myung-Mook Lee,
Kyu-Hyung Ryu
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ABSTRACT: Metabolic syndrome (MetS) increases the risk of heart failure (HF). The purpose of this study was to identify the prevalence of MetS in patients with HF and determine the syndrome's association with HF in clinical and laboratory parameters.
A total of 3200 HF patients (67.6±14.5 years) enrolled in a nationwide prospective Korea HF Registry between Jan. 2005 and Oct. 2009. Patients were divided into two groups according to the presence or absence of MetS at admission: group I (presence, n=1141) and group II (absence, n=2059).
The prevalence of MetS was 35.7% across all subjects and was higher in females (56.0%). The levels of white blood cells, platelets, creatinine, glucose, and cholesterol were significantly higher in group I than in group II. Left ventricular dimension and volume was smaller and ejection fraction was higher in group I than in group II. An ischemic cause of HF was more frequent in group I. The rates of valvular and idiopathic cause were lower in group I than in group II. The rate of mortality was lower in group I than in group II (4.9% vs. 8.3%, p<0.001).
Despite the increased cardiovascular risks in MetS, MetS was found to be associated with decreased mortality in HF.
Korean Circulation Journal 02/2013; 43(2):87-92.
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Keun-Ho Park,
Myung Ho Jeong,
Jong Min Kim,
Dae Sung Park,
Jung Ha Kim,
Kyung Seob Lim,
Ki Hong Lee,
Doo Sun Sim,
Hyun Ju Yoon,
Nam Sik Yoon,
Kye Hun Kim,
Hyung Wook Park,
Young Joon Hong,
Ju Han Kim, Youngkeun Ahn,
Jeong Gwan Cho,
Jong Chun Park,
Jung Chaee Kang
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ABSTRACT: BACKGROUND: This study was conducted to evaluate the endothelialization and the inflammatory responses depending on the administration duration of triple anti-platelet therapy at overlapping bioabsorbable polymer coated biolimus-eluting stents (BESs) in a porcine coronary model. METHODS: We successfully deployed 36 overlapping BESs for the left anterior descending coronary and left circumflex artery or right coronary artery in 18 non-injured pigs. Total pigs were divided into 3 groups (12 overlapping stents of 6 pigs in each group) as follows: group I received aspirin 100mg and clopidogrel 75mg daily for 8weeks, group II received aspirin 100mg and clopidogrel 75mg daily for 8weeks and cilostazol 200mg daily for initial 4weeks, and group III received aspirin 100mg, clopidogrel 75mg, and cilostazol 200mg daily for 8weeks. Follow-up coronary angiograms and histomorphometric and histopahtologic analyses at overlapping and non-overlapping segments were performed respectively. RESULTS: Inflammation score was similar between overlapping and non-overlapping segments in all pigs (1.2±0.33 vs. 1.1±0.17, p=0.117). The neointima area (NA) and percent area stenosis (%AS) at overlapping segments were not significantly different among the 3 groups. However, at non-overlapping segments, NA and %AS in group III were significantly smaller than those in group I (2.3±0.50mm(2) vs. 1.8±0.43mm(2), p=0.037; 48.9±12.85% vs. 37.7±9.08%, p=0.031). CONCLUSIONS: Our study shows that BES appears to be reliable on the inflammatory response at overlapping segments as well as non-overlapping segments. Long-term administration of cilostazol is more effective in reducing neointimal formation at non-overlapping segments of BESs in a porcine coronary model.
International journal of cardiology 01/2013; · 7.08 Impact Factor
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The Korean Journal of Internal Medicine 01/2013; 28(1):112-5.
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Shi Hyun Rhew, Youngkeun Ahn,
Eun Ae Cho,
Min Sok Kim,
Su Young Jang,
Ki Hong Lee,
Min Goo Lee,
Keun Ho Park,
Doo Sun Sim,
Young Joon Hong,
Ju Han Kim,
Myung Ho Jeong
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ABSTRACT: Drug-eluting stents (DES) have gained great popularity because of extraordinarily low rates of restenosis. Despite these superior clinical outcomes, several cases regarding the severe multi-vessel coronary spasm, although rare, after the placement of first generation DES have been reported. We report a case of severe, multi-vessel coronary spasm that occurred two occasions after placement of a zotarolimus-eluting stent, one of the second generation DES, in a 42-year-old man with unstable angina. The first incidence was relieved by intracoronary nitroglycerin alone, and second incident, which had combined fixed stenosis was treated with intracoronary nitroglycerin and everolimus-eluting stent.
Korean Circulation Journal 01/2013; 43(1):48-53.
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Daisuke Hachinohe,
Myung Ho Jeong,
Shigeru Saito,
Min Chol Kim,
Kyung Hoon Cho,
Khurshid Ahmed,
Seung Hwan Hwang,
Min Goo Lee,
Doo Sun Sim,
Keun-Ho Park, [......],
Taek Jong Hong,
Donghoon Choi,
Myeong Chan Cho,
Chong Jin Kim,
Ki Bae Seung,
Wook Sung Chung,
Yang Soo Jang,
Seung Woon Rha,
Jang Ho Bae,
Seung Jung Park
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ABSTRACT: To determine which drug-eluting stents are more effective in acute myocardial infarction (MI) patients with chronic kidney disease (CKD).
This study included a total of 3,566 acute MI survivors with CKD from the Korea Acute Myocardial Infarction Registry who were treated with stenting and followed up for 12 months: 1,845 patients who received sirolimus-eluting stents (SES), 1,356 who received paclitaxel-eluting stents (PES), and 365 who received zotarolimus-eluting stents (ZES). CKD was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m(2) calculated by the modification of diet in renal disease method.
At the 12-month follow-up, patients receiving ZES demonstrated a higher incidence (14.8%) of major adverse cardiac events (MACEs) compared to those receiving SES (10.1%) and PES (12%, p = 0.019). The ZES patients also had a higher incidence (3.9%) of target lesion revascularization (TLR) compared to those receiving SES (1.5%) and PES (2.4%, p = 0.011). After adjusting for confounding factors, ZES was associated with a higher incidence of MACE and TLR than SES (adjusted hazard ratio [HR], 0.623; 95% confidence interval [CI], 0.442 to 0.879; p = 0.007; adjusted HR, 0.350; 95% CI, 0.165 to 0.743; p = 0.006, respectively), and with a higher rate of TLR than PES (adjusted HR, 0.471; 95% CI, 0.223 to 0.997; p = 0.049).
Our findings suggest that ZES is less effective than SES and PES in terms of 12-month TLR, and has a higher incidence of MACE due to a higher TLR rate compared with SES, in acute MI patients with CKD.
The Korean Journal of Internal Medicine 12/2012; 27(4):397-406.
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Khurshid Ahmed,
Myung Ho Jeong,
Rabin Chakraborty,
Sumera Ahmed,
Young Joon Hong,
Doo Sun Sim,
Keun Ho Park,
Ju Han Kim, Youngkeun Ahn,
Jung Chaee Kang,
Myeong Chan Cho,
Chong Jin Kim,
Young Jo Kim
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ABSTRACT: Chronic kidney disease (CKD) is associated with poor outcomes after percutaneous coronary intervention (PCI). We sought to compare different coronary stents used during primary PCI in patients with ST-elevation myocardial infarction (STEMI) and CKD.
We selected 2408 consecutive STEMI patients with CKD (estimated glomerular filtration rate <60 mL/min/1.73 m(2)) undergoing primary PCI and divided them into 5 groups based on the type of stent implanted: 1) bare metal stent (BMS), 2) paclitaxel-eluting stent (PES), 3) sirolimus-eluting stent (SES), 4) zotarolimus-eluting stent (ZES), or 5) everolimus-eluting stent (EES). The study endpoint was the number of major adverse cardiac events (MACE) at 12 months.
There was no significant difference in the incidence of 12-month myocardial infarction, target lesion revascularization, or target vessel revascularization between stent groups; however, the overall rate of repeat revascularization differed significantly between groups. All-cause death differed significantly among the groups. The incidence of 12-month MACE in BMS, PES, SES, ZES, and EES was 8.3%, 9.8%, 8.6%, 5.5%, and 2.6%, respectively (p<0.001). Kaplan-Meier analysis did not show a significant differences in 12-month MACE-free survival among the groups (log-rank p=0.076). This finding remained the same after adjusting for multiple confounders (p=0.147).
Any of the 5 stents can be used to treat STEMI patients with CKD undergoing primary PCI; all have similar risk of 12-month MACE. This result is hypothesis-generating and warrants further evaluation with a long-term randomized study.
Korean Circulation Journal 12/2012; 42(12):830-8.
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Min Chul Kim, Youngkeun Ahn,
Keun Ho Park,
Doo Sun Sim,
Nam Sik Yoon,
Hyun Ju Yoon,
Kye Hun Kim,
Young Joon Hong,
Hyung Wook Park,
Ju Han Kim,
Myung Ho Jeong,
Jeong Gwan Cho,
Jong Chun Park,
Jung Chaee Kang
International journal of cardiology 11/2012; · 7.08 Impact Factor
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Khurshid Ahmed,
Myung Ho Jeong,
Rabin Chakraborty,
Young Joon Hong,
Doo Sun Sim,
Sumera Ahmed,
Seung Hwan Hwang,
Min Goo Lee,
Keun Ho Park,
Ju Han Kim, Youngkeun Ahn,
Myeong Chan Cho,
Chong Jin Kim,
Young Jo Kim,
Jong Chun Park,
Jung Chaee Kang
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ABSTRACT: The aim of this study was to compare safety and efficacy of 4 homogenous overlapping drug-eluting stents (DES) in acute myocardial infarction (AMI) patients. We selected 1,349 consecutive patients (62.1 ± 14.9 yr, 69.4% male) who received homogenous overlapping DESs in diffuse de novo coronary lesions from Korea Acute Myocardial Infarction Registry from April 2006 through September 2010. They were divided into 4 groups based on type of DES implanted - Paclitaxel (PES), Sirolimus (SES), Zotarolimus (ZES) and Everolimus (EES)-eluting stents. Primary endpoint was 12-month MACE. We also studied EES versus other DESs (PES + SES + ZES). Mean stent length was 26.2 ± 7.5 mm and mean stent diameter was 3.1 ± 0.4 mm. Average number of stents used per vessel was 2.2 ± 0.5. Incidence of major adverse cardiac events (MACE) in PES, SES, ZES, and EES groups were 9.5%, 9.2%, 7.5%, and 3.8%, respectively (P = 0.013). In EES group, overall MACE and repeat revascularization were lowest, and no incidence of stent thrombosis was observed. Non-fatal MI was highest in PES, almost similar in SES and EES with no incidence in ZES group (P = 0.044). Cox proportional hazard analysis revealed no differences in the incidence of primary endpoint (P = 0.409). This study shows no significant differences in 12-month MACE among 4 groups.
Journal of Korean medical science 11/2012; 27(11):1339-1346. · 0.84 Impact Factor
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Doo Hwan Lee,
Myung Ho Jeong,
Jung Ae Rhee,
Jin Su Choi,
Ki Hong Lee,
Min Goo Lee,
Doo Sun Sim,
Keun-Ho Park,
Nam Sik Yoon,
Hyun Ju Yoon,
Kye Hun Kim,
Hyung Wook Park,
Young Joon Hong,
Ju Han Kim, Youngkeun Ahn,
Jeong Gwan Cho,
Jong Chun Park,
Jung Chaee Kang
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ABSTRACT: Predictive factors of mortality in acute coronary syndrome (ACS) patients with left ventricular dysfunction were analyzed during 5-year clinical follow-up after percutaneous coronary intervention (PCI).
A total of 329 ACS consecutive patients (64.6±11.3 years, 227 males) who underwent PCI from January 2001 to March 2006 were followed for 5 years. All patients had lower than 40% of left ventricular ejection fraction (LVEF). Patients were divided into Group I (survived longer than 5-years: n=130, 101 males) and Group II (survived shorter than 5 years: n=199, 126 males).
The cumulative survival rate was 88.0% at 1 month, 78.0% at 6 months, 75.0% at 1 year, 67.0% at 2 years, 62.0% at 3 years, 57.0% at 4 years and 40% at 5-years. Group II was older (61.6±11.2 years vs. 66.4±11.4 years, p<0.001), and showed higher prevalence of female gender (28.4% vs. 36.7%, p=0.006) and lower LVEF (35.3±5.2 vs. 33.6±5.6) than Group I. The independent predictors for mortality were LVEF <30% {odds ratio (OR)=1.793, 95% confidence interval (CI): 1.234-2.452, p=0.002}, serum creatinine >3.0 mg/dL (OR=2.455, 95% CI: 1.306-4.614, p=0.005), older than 65 years (OR=1.594, 95% CI: 1.152-2.206, p=0.005), and female gender (OR=1.524, 95% CI: 1.090-2.130, p=0.014).
Five-year survival rate was 40% in ACS patients with left ventricular dysfunction, and the predictors for mortality were low LVEF, high serum creatinine, old age, and female gender.
Korean Circulation Journal 10/2012; 42(10):692-7.
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Doo Sun Sim,
Myung Ho Jeong,
Kyoung Rae Cha,
Suk Ho Park,
Jong Oh Park,
Young Min Shin,
Heungsoo Shin,
Young Joon Hong, Youngkeun Ahn,
Robert S Schwartz,
Jung Chaee Kang
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ABSTRACT: BACKGROUND: Chronic total occlusion (CTO) remains a challenge in interventional cardiology. We investigated the feasibility and reliability of copper wire stents and levo-polylactic acid (l-PLA) as a means of CTO induction in a porcine model. METHODS AND RESULTS: In one group of 20 swine, copper stents were crimped on a 3.0mm angioplasty balloon and inserted into the mid-left anterior descending coronary artery (LAD). In the other group of 20 swine, l-PLA was wrapped on a guidewire and pushed into the distal LAD with a 3.0mm balloon catheter to induce embolization. Of 20 swine which underwent copper stent implantation, 13 died of stent thrombosis. In the remaining 7 swine, total or near total occlusion with collateral circulation was observed at 5weeks. Of 20 swine which underwent l-PLA embolization, 4 died of ventricular fibrillation during or shortly after the procedure. Serial histopathologic studies showed complete absorption of the polymer with replacement by fibrotic tissue approximately 4weeks following the polymer implantation. CONCLUSIONS: CTO could be reliably induced in porcine coronary arteries by copper stents and l-PLA. These models may support investigation of new percutaneous devices to facilitate CTO interventions.
Journal of Cardiology 09/2012; · 1.28 Impact Factor
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Hui-Lian Che,
In-Ho Bae,
Kyung Seob Lim,
In Taek Song,
Haeshin Lee,
Muthunarayanan Muthiah,
Ran Namgung,
Won Jong Kim,
Dong-Gon Kim, Youngkeun Ahn,
Myung-Ho Jeong,
In-Kyu Park
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ABSTRACT: Restenosis is the formation of blockages occurring at the site of angioplasty or stent placement. In order to avoid such blockages, the suppression of smooth muscle cells near the implanted stent is required. The Akt1 protein is known to be responsible for cellular proliferation, and specific inhibition of Akt1 gene expression results in the retardation of cell growth. To take advantage of these benefits, we developed a new delivery technique for Akt1 siRNA nanoparticles from a hyaluronic acid (HA)-coated stent surface. For this purpose, the disulfide cross-linked low molecular polyethyleneimine (PEI) (ssPEI) was used as a gene delivery carrier because disulfide bonds are stable in an oxidative extracellular environment but degrade rapidly in reductive intracellular environments. In this study, Akt1 siRNA showed efficient ionic interaction with the ssPEI carrier, which was confirmed by polyacrylamide gel electrophoresis. Akt1 siRNA/ssPEI nanoparticles (ASNs) were immobilized on the HA-coated stent surface and exhibited stable binding and localization, followed by time-dependent sustained release for intracellular uptake. Cellular viability on the nanoparticle-immobilized surface was assessed using A10 vascular smooth muscle cells, and the results revealed that immobilized ASNs exhibited negligible cytotoxicity against the adhering A10 cells. Transfection efficiency was quantified using a luciferase assay; the transgene expression of Akt1 suppression through the delivered Akt1 siRNA was measured using RT-PCR and western blot, demonstrating higher gene silencing efficiency when compared to other carriers. ASN coated on HA stents were deployed in the balloon-injured external iliac artery in rabbits in vivo. It was shown that the Akt1 released from the stent suppressed the growth of the smooth muscle at the peri-stent implantation area, resulting in the prevention of restenosis in the post-implantation phase.
Biomaterials 08/2012; 33(33):8548-56. · 7.40 Impact Factor
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ABSTRACT: BACKGROUND: The aim of this study was to investigate a useful cardiac biomarker for predicting echocardiographic right ventricular (RV) dysfunction in patients with acute pulmonary embolism (APE). METHODS: A total of 84 patients with APE were divided into two groups: patients with RV dysfunction (group I, n=51, 61.8±15.1 years) versus without RV dysfunction (group II, n=33, 66.8±13.6 years). Cardiac biomarkers were compared between the groups. RESULTS: The level of N-terminal pro-brain-type natriuretic peptide (NT-proBNP), cardiac specific troponin T (cTnt), and I (cTni) was significantly elevated in group I compared to group II, but the level of creatine kinase and high-sensitivity C-reactive protein was not different. By receiver operating characteristic curve analysis, the area under the curve to predict RV dysfunction was 0.912 for NT-proBNP, 0.797 for cTnt, and 0.766 for cTni. The optimal cut-off value to predict RV dysfunction was 620.0pg/mL for NT-proBNP (sensitivity: 90.2%, specificity: 75.8%), 0.016ng/mL for cTnt (sensitivity: 82.4%, specificity: 78.8%), and 0.055ng/mL for cTni (sensitivity: 86.3%, specificity: 66.7%). NT-proBNP>620pg/mL and cTnt>0.016ng/mL were independent predictors of RV dysfunction on multivariate analysis after adjustment for the baseline characteristics. CONCLUSIONS: NT-proBNP, cTnt, and cTni were significant serologic predictors of RV dysfunction in APE. Measurements of NT-proBNP, cTnt, and cTni are simple and useful in the risk stratification or treatment of APE.
Journal of Cardiology 08/2012; · 1.28 Impact Factor
