Slide Session : OS-CAD-09 ; Cardiology : Benefi t of Statin Therapy in Patients with Coronary Spasm-Induced Acute Myocardial Infarction

( Zhe Hao Piao ),( Myung Ho Jeong ),( Young Keun Ahn ),( Young Jo Kim ),( Myeong Chan Cho ),( Chong Jin Kim ),( Hyo Soo Kim ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: Coronary spasm is associated with endothelial dysfunction and statins have been shown to improve endothelial function. However, the benefit of statin therapy in patients with coronary spasm-induced acute myocardial infarction (AMI) is remains unclear. The purpose of this study was to determine whether statin therapy beneficial in patients with coronary spasm-induced AMI. Methods: We analyzed 501 patients with coronary spasm-induced AMI and survived at discharge from the Korean AMI Registry between November 2005 and May 2013. They were divided into 2 groups according to the prescribing of statins at discharge (statin group n = 292; nonstatin group n = 209). The primary endpoint was the composite of 1-year major adverse cardiac events, including death, recurrent MI, target vessel revascularization. Results: During a median follow-up of 346 days, the primary end points occurred in 17 patients. Statin therapy significantly reduced the risk of the composite primary endpoint (adjusted hazard ratio [HR]: 0.30; 95% confidence interval [CI]: 0.09 to 0.97; p = 0.045). Statin therapy reduced the risk of myocardial infarction (HR: 0.19; 95% CI: 0.04 to 0.93; p = 0.040). However, there was no difference in the risk of the composite of all-cause death. Conclusions: Statin therapy in patients with coronary spasm-induced AMI was associated with improved clinical outcome.

Benefits of Statin Therapy in Patients With Acute Myocardial Infarction With Serum Low-Density Lipoprotein Cholesterol ≤ 50 mg/dl

Piao, Zhe Hao,Jin, Li,Kim, Ju Han,Ahn, Youngkeun,Kim, Young Jo,Cho, Myeong Chan,Kim, Chong Jin,Kim, Hyo Soo,Liu, Bin,Jeong, Myung Ho Elsevier 2017 The American journal of cardiology Vol.120 No.2

<P>Previous trials have found that statin therapy reduces low-density lipoprotein cholesterol (LDL-C) level and the risk of cardiovascular events. However, the benefit of statin therapy in patients with baseline LDL-C levels ≤ 50 mg/dl is less clear. Therefore, the aim of this study was to assess whether patients with acute myocardial infarction (AMI) who have baseline LDL-C levels ≤ 50 mg/dl would benefit from statin therapy in real-world clinical practice. We analyzed the clinical data of 1,048 patients (67.3 ± 12.6 years, 69.6% men) with AMI, who had baseline LDL-C levels ≤ 50 mg/dl from the Korean Acute Myocardial Infarction Registry data between November 2005 and May 2014. They were divided into 2 groups based on whether they were prescribed statins or not at discharge (statin and nonstatin group, n = 738 and 310, respectively). The primary end point was the major adverse cardiac event (MACE), defined as the composite of all-cause mortality, recurrent myocardial infarction, and repeated percutaneous coronary intervention or coronary artery bypass grafting. MACE occurred in 9.2% of the statin group versus 19.6% in the nonstatin group during the 12-month follow-up. Statin therapy significantly reduced the risk of MACE (hazard ratio [HR] 0.60, 95% CI 0.39 to 0.94, p = 0.025) and coronary artery bypass grafting (HR 0.27, 95% CI 0.08 to 0.96, p = 0.043). There was a trend of reduced cardiac death in the statin group compared with the nonstatin group (HR 0.52, 95% CI 0.26 to 1.02, p = 0.059). Statin therapy for patients with AMI with LDL-C levels ≤ 50 mg/dl was associated with improved outcomes. Therefore, statin therapy is feasible and effective, even in AMI patients with extremely low levels of LDL-C.</P>

S-228 : Early Intervention in Octogenarians with Non-ST-Elevation Myocardial Infarction

( Zhe Hao Piao ),( Myung Ho Jeong ),( Jae Yeong Cho ),( Hae Chang Jeong ),( Keun-ho Park ),( Doo Sun Sim ),( Nam Sik Yoon ),( Hyun Ju Yoon ),( Young Joon Hong ),( Kye Hun Kim ),( Ju Han Kim ),( Youngk 대한내과학회 2013 대한내과학회 추계학술대회 Vol.2013 No.1

Background and Objectives: Octogenarians with coronary artery disease constitute a high risk group. Most studies documented that octogenarians with non-ST-elevation myocardial infarction (NSTEMI) may derive a greater benefit from an invasive strategy than younger patients, but the optimal timing of such intervention is not well established. We hypothesized that octogenarians with NSTEMI who underwent earlier intervention in the invasive arm would have improved outcomes. Methods: We retrospectively analyzed 567 octogenarians who underwent percutaneous coronary intervention (PCI) and who were enrolled in the Korean Acute Myocardial Infarction Registry. They were divided into 2 groups, an early intervention (PCI done within 24 hours after onset of symptoms; n=228) and deferred intervention (24 to 72 hours; n=339). The primary outcome was the incidence of in hospital death and major bleeding. Secondary clinical endpoints were the 12-month all-cause death and 12-month major adverse cardiac events (MACE), where MACE included all-cause death, recurrent myocardial infarction, target lesion revascularization (TLR), and coronary artery bypass grafting (CABG). Results: There were no significant differences in the incidence of in hospital death (6.4 vs. 5.9%: p=0.808) and major bleeding (0.0 vs. 3.0%: p=0.110) between groups. The secondary clinical endpoints were similar between two groups during 12-month follow-up: all-cause death (8.0 vs. 11.5%: p=0.936), MACE (11.3 vs. 16.9%: p=0.897), recurrent myocardial infarction (0.9 vs. 0.5%: p=0.484), TLR (1.8 vs. 1.6%: p=0.693) and CABG (0.0 vs. 0.5%: p=0.678). Conclusions: In octogenarians with NSTEMI, an early intervention approach does not offer an advantage over a deferred intervention.

Coronary Artery Fistula with Giant Aneurysm and Coronary Stenosis Treated by Transcatheter Embolization and Stent

Zhe Hao Piao,정명호,정해창,박근호,심두선,홍영준,김주한,안영근 대한심장학회 2015 Korean Circulation Journal Vol.45 No.3

Coronary artery fistula (CAF) with giant aneurysm and accompanied by coronary artery stenosis is a very rare disease. Herein, we report a case of a 76-year-old woman having a complex coronary-to-pulmonary artery fistula associated with a giant aneurysm and accompanied by coronary artery stenosis. The patient was successfully treated using transcatheter coil embolization and coronary stent implantation. Eight years later, we performed a follow-up coronary angiogram, which revealed the CAF and the aneurysm were completely occluded and previous stent patency

Gallic acid attenuates calcium calmodulin‐dependent kinase II‐induced apoptosis in spontaneously hypertensive rats

Jin, Li,Piao, Zhe Hao,Liu, Chun Ping,Sun, Simei,Liu, Bin,Kim, Gwi Ran,Choi, Sin Young,Ryu, Yuhee,Kee, Hae Jin,Jeong, Myung Ho John Wiley and Sons Inc. 2018 JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Vol.22 No.3

<P><B>Abstract</B></P><P>Hypertension causes cardiac hypertrophy and leads to heart failure. Apoptotic cells are common in hypertensive hearts. Ca<SUP>2+</SUP>/calmodulin‐dependent protein kinase II (CaMKII) is associated with apoptosis. We recently demonstrated that gallic acid reduces nitric oxide synthase inhibition‐induced hypertension. Gallic acid is a trihydroxybenzoic acid and has been shown to have beneficial effects, such as anti‐cancer, anti‐calcification and anti‐oxidant activity. The purpose of this study was to determine whether gallic acid regulates cardiac hypertrophy and apoptosis in essential hypertension. Gallic acid significantly lowered systolic and diastolic blood pressure in spontaneously hypertensive rats (SHRs). Wheat germ agglutinin (WGA) and H&E staining revealed that gallic acid reduced cardiac enlargement in SHRs. Gallic acid treatment decreased cardiac hypertrophy marker genes, including atrial natriuretic peptide (<I>ANP</I>) and brain natriuretic peptide (<I>BNP</I>), in SHRs. The four isoforms, α, β, δ and γ, of <I>CaMKII</I> were increased in SHRs and were significantly reduced by gallic acid administration. Gallic acid reduced cleaved caspase‐3 protein as well as <I>bax</I>,<I> p53</I> and <I>p300 </I>mRNA levels in SHRs. <I>CaMKII</I> δ overexpression induced <I>bax</I> and <I>p53</I> expression, which was attenuated by gallic acid treatment in H9c2 cells. Gallic acid treatment reduced DNA fragmentation and the TUNEL positive cells induced by angiotensin II. Taken together, gallic acid could be a novel therapeutic for the treatment of hypertension through suppression of CaMKII δ‐induced apoptosis.</P>

Gallic acid attenuates hypertension, cardiac remodeling, and fibrosis in mice with NG-nitro-L-arginine methyl ester-induced hypertension via regulation of histone deacetylase 1 or histone deacetylase 2

Jin, Li,Lin, Ming Quan,Piao, Zhe Hao,Cho, Jae Yeong,Kim, Gwi Ran,Choi, Sin Young,Ryu, Yuhee,Sun, Simei,Kee, Hae Jin,Jeong, Myung Ho Lippincott Williams & Wilkins 2017 Journal of Hypertension Vol.35 No.7

OBJECTIVE:: Gallic acid, a natural chemical found in plants, has been reported to show antioxidant, anticancer, and anti-inflammatory effects. We investigated the efficacy of a short-term or long-term treatment with gallic acid in N-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive mice and the underlying regulatory mechanism. METHODS:: Hypertension was sufficiently induced after 2 weeks of L-NAME administration. Cardiac remodeling was assessed by echocardiography. Hypertrophic markers, transcription factors, and fibrosis-related gene expression were evaluated by quantitative real-time polymerase chain reaction and western blotting. RESULTS:: Gallic acid effectively lowered SBP, regardless of the administration route (intraperitoneal or oral). L-NAME increased the left ventricular (LV) thickness without an increase in the total heart weight. Weekly echocardiography demonstrated that gallic acid significantly reduced LV posterior wall and septum thickness in chronic L-NAME mice from 3 to 7 weeks. The administration of gallic acid to mice showed a dual preventive and therapeutic effect on the L-NAME-induced LV remodeling. The effect was associated with the suppression of the gene expression of hypertrophy markers and the GATA-binding factor 6 (GATA6) transcription factor. Short-term or long-term treatment with gallic acid attenuated cardiac fibrosis and reduced the expression of histone deacetylase 1 and 2 in H9c2 cells and in rat primary cardiac fibroblasts, as well as in vivo. Small interfering RNA knockdown confirmed the association of these enzymes with L-NAME-induced cardiac remodeling and fibrosis. CONCLUSION:: These results suggested that gallic acid may be a potential therapeutic agent for the treatment of cardiovascular diseases with hypertension and cardiac fibrosis.

<i>Dendropanax morbifera</i> Prevents Cardiomyocyte Hypertrophy by Inhibiting the Sp1/GATA4 Pathway

Sun, Simei,Li, Tianyi,Jin, Li,Piao, Zhe Hao,Liu, Bin,Ryu, Yuhee,Choi, Sin Young,Kim, Gwi Ran,Jeong, Ji Eun,Wi, An Jin,Lee, Song Ju,Kee, Hae Jin,Jeong, Myung Ho World Scientific Publishing Company 2018 The American journal of Chinese medicine Vol.46 No.5

<P>An extract of <I>Dendropanax morbifera</I> branch exerts antioxidant, anti-inflammatory, antithrombotic, and anticancer activities. The purpose of this study was to investigate the effect of the extract in isoproterenol-induced cardiac hypertrophy. Phalloidin staining showed that treatment with the extract dramatically prevents isoproterenol-induced H9c2 cell enlargement and the expression of cardiac hypertrophic marker genes, including atrial natriuretic peptide (ANP) and B-type brain natriuretic peptide (BNP). Further, pretreatment with the extract decreased isoproterenol-induced GATA4 and Sp1 expression in H9c2 cells. Overexpression of Sp1 induced the expression of GATA4. The forced expression of Sp1 or its downstream target GATA4, as well as the co-transfection of Sp1 and GATA4 increased the expression of ANP, which was decreased by treatment with the extract. To further elucidate the regulation of the Sp1/GATA4-mediated expression of ANP, knockdown experiments were performed. Transfection with small interfering RNAs (siRNAs) for Sp1 or GATA4 decreased ANP expression. The extract did not further inhibit the expression of ANP reduced by the transfection of GATA4 siRNA. Sp1 knockdown did not affect the expression of ANP that was induced by the overexpression of GATA4; however, GATA4 knockdown abolished the expression of ANP that had been induced by Sp1 overexpression. The extract treatment also attenuated the isoproterenol-induced activation of p38 MAPK, ERK1/2, and JNK1. Hesperidin, catechin, 2,5-dihydroxybenzoic acid, and salicylic acid are the main phenolic compounds present in the extract as observed by high performance liquid chromatography. Hesperidin and 2,5-dihydroxybenzoic acid attenuated isoproterenol-induced cardiac hypertrophy. These findings suggest that the <I>D. morbifera</I> branch extract prevents cardiac hypertrophy by downregulating the activation of Sp1/GATA4 and MAPK signaling pathways.</P>

Expression of Class I and Class II a/b Histone Deacetylase is Dysregulated in Hypertensive Animal Models

기해진,김귀란,Ming Quan Lin,최신영,류유희,Li Jin,Zhe Hao Piao,정명호 대한심장학회 2017 Korean Circulation Journal Vol.47 No.3

Background and Objectives: Dysregulation of histone deacetylase expression and enzymatic activity is associated with a number of diseases. It has been reported that protein levels of histone deacetylase (HDAC)1 and HDAC5 increase during human pulmonary hypertension, and that the enzymatic activity of HDAC6 is induced in a chronic hypertensive animal model. This study investigated the protein expression profiles of class I and II a/b HDACs in three systemic hypertension models. Materials and Methods: We used three different hypertensive animal models: (i) Wistar-Kyoto rats (n=8) and spontaneously hypertensive rats (SHR; n=8), (ii) mice infused with saline or angiotensin II to induce hypertension, via osmotic mini-pump for 2 weeks, and (iii) mice that were allowed to drink L-NG-nitro-L-arginine methyl ester (L-NAME) to induce hypertension. Results: SHR showed high systolic, diastolic, and mean blood pressures. Similar increases in systolic blood pressure were observed in angiotensin II or L-NAME-induced hypertensive mice. In SHR, class IIa HDAC (HDAC4, 5, and 7) and class IIb HDAC (HDAC6 and 10) protein expression were significantly increased. In addition, a HDAC3 protein expression was induced in SHR. However, in L-NAME mice, class IIa HDAC protein levels (HDAC4, 5, 7, and 9) were significantly reduced. HDAC8 protein levels were significantly reduced both in angiotensin II mice and in SHR. Conclusion: These results indicate that dysregulation of class I and class II HDAC protein is closely associated with chronic hypertension.