Sungha Park

University of Seoul, Sŏul, Seoul, South Korea

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Publications (170)555.97 Total impact

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    ABSTRACT: Purpose: Elastin is a major arterial structural protein, and elastin-derived peptides are related to arterial change. We previously reported on a novel assay developed using aortic elastin peptides; however, its clinical implications remain unclear. In this study, we assessed whether anti-elastin antibody titers reflect the risk of coronary artery disease (CAD) or its characteristics. Materials and Methods: We included 174 CAD patients and 171 age- and sex-matched controls. Anti-elastin antibody titers were quantified by enzyme-linked immunosorbent assay. Parameters of arterial stiffness, including the augmentation index (AI) and heart-to-femoral pulse wave velocity (hfPWV), were measured non-invasively. The clinical and angiographic characteristics of CAD patients were also evaluated. Associations between anti-elastin levels and vascular characteristics were examined by linear regression analysis. Results: The median blood level of anti-elastin was significantly lower in the CAD group than in the controls [197 arbitrary unit (a.u.) vs. 63 a.u., p<0.001]. Levels of anti-elastin were significantly lower in men and in subjects with hypertension, diabetes mellitus, hyperlipidemia, or high hfPWV. Nevertheless, anti-elastin levels were not dependent on atherothrombotic events or the angiographic severity of CAD. In a multivariate analysis, male sex (β=-0.38, p<0.001), diabetes mellitus (β=-0.62, p<0.001), hyperlipidemia (β=-0.29, p<0.001), and AI (β=-0.006, p=0.02) were ultimately identified as determinants of anti-elastin levels. Conclusion: Lower levels of anti-elastin are related to CAD. The association between antibody titers and CAD is linked to arterial stiffness rather than the advancement of atherosclerosis.
    Yonsei Medical Journal 11/2015; 56(6):1545. DOI:10.3349/ymj.2015.56.6.1545 · 1.29 Impact Factor

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    ABSTRACT: Resistant hypertension (HTN) occurs in 15-20% of treated hypertensive patients, and 70-80% of resistant hypertensive patients have obstructive sleep apnea (OSA). The characteristics of resistant HTN that predispose patients to OSA have not been reported. Therefore, we aimed to determine the clinical, laboratory, and polysomnographic features of resistant HTN that are significantly associated with OSA. Hypertensive patients (n=475) who underwent portable polysomnography were enrolled. The patients were categorized into controlled (n=410) and resistant HTN (n=65) groups. The risk factors for the occurrence of OSA in controlled and resistant hypertensive patients were compared, and independent risk factors that are associated with OSA were analyzed. Out of 475 patients, 359 (75.6%) were diagnosed with OSA. The prevalence of OSA in resistant HTN was 87.7%, which was significantly higher than that in controlled HTN (73.7%). Age, body mass index, neck circumference, waist circumference, and hip circumference were significantly higher in OSA. However, stepwise multivariate analyses revealed that resistant HTN was not an independent risk factor of OSA. The higher prevalence and severity of OSA in resistant HTN may be due to the association of risk factors that are common to both conditions.
    Yonsei medical journal 09/2015; 56(5):1258-65. DOI:10.3349/ymj.2015.56.5.1258 · 1.29 Impact Factor
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    ABSTRACT: Insulin inhibits ischemia/reperfusion-induced myocardial apoptosis through the PI3K/Akt/mTOR pathway. Survivin is a key regulator of anti-apoptosis against doxorubicin-induced cardiotoxicity. Insulin increases survivin expression in cardiac myocytes to mediate cytoprotection. However, the mechanism by which survivin mediates the protective effect of insulin against doxorubicin-associated injury remains to be determined. In this study, we demonstrated that pretreatment of H9c2 cardiac myocytes with insulin resulted in a significant decrease in doxorubicin-induced apoptotic cell death by reducing cytochrome c release and caspase-3 activation. Doxorubicin-induced reduction of survivin mRNA and protein levels was also significantly perturbed by insulin pretreatment. Reducing survivin expression with survivin siRNA abrogated insulin-mediated inhibition of caspase-3 activation, suggesting that insulin signals to survivin inhibited caspase-3 activation. Interestingly, pretreatment of H9c2 cells with insulin or MG132, a proteasome inhibitor, inhibited doxorubicin-induced degradation of the transcription factor Sp1. ChIP assay showed that pretreatment with insulin inhibited doxorubicin-stimulated Sp1 dissociation from the survivin promoter. Finally using pharmacological inhibitors of the PI3K pathway, we showed that insulin-mediated activation of the PI3K/Akt/mTORC1 pathway prevented doxorubicin-induced proteasome-mediated degradation of Sp1. Taken together, insulin pretreatment confers a protective effect against doxorubicin-induced cardiotoxicity by promoting Sp1-mediated transactivation of survivin to inhibit apoptosis. Our study is the first to define a role for survivin in cellular protection by insulin against doxorubicin-associated injury and show that Sp1 is a critical factor in the transcriptional regulation of survivin.
    PLoS ONE 08/2015; 10(8):e0135438. DOI:10.1371/journal.pone.0135438 · 3.23 Impact Factor
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    ABSTRACT: In end-stage renal disease, deleterious effect of sarcopenia on cardiovascular disease has been explained mainly by chronic inflammation. However, evidence emerged that skeletal muscles mediate their protective effect against sarcopenia by secreting myokines. Therefore, we sought to investigate the effect of irisin, a recently introduced myokine, on the association between sarcopenia and cardiovascular disease in peritoneal dialysis (PD) patients. Serum irisin concentrations were assessed by enzyme-linked immunosorbent assay in 102 prevalent PD patients and 35 age- and sex-matched controls. To determine sarcopenia and cardiovascular disease, anthropometric indices including mid-arm muscle circumference (MAMC) and carotid intima-media thickness (cIMT) were measured. Serum irisin concentrations were significantly lower in PD patients than in controls (184.2 ± 88.0 vs. 457.2 ± 105.5 ng/mL, P < 0.001). In PD patients, univariate linear regression analysis showed that serum irisin was positively correlated with MAMC and thigh circumference, but negatively correlated with residual renal function and cIMT. Multivariate analysis revealed that MAMC (per 1 cm increase, B = 8.78, 95% confidence interval [CI] = 0.77-16.79, P = 0.03) had an independent association with serum irisin. In addition, serum irisin was a significant independent predictor for carotid atherosclerosis even after adjustment for high-sensitivity C-reactive protein in PD patients (per 1 g/mL increase, odds ratio = 0.990, 95% CI = 0.982-0.997, P = 0.007). This study demonstrated that serum irisin was significantly associated with sarcopenia and carotid atherosclerosis in PD patients. Additional studies to provide a confirmation and examine possible mechanisms are warranted. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Atherosclerosis 08/2015; 242(2):476-482. DOI:10.1016/j.atherosclerosis.2015.08.002 · 3.99 Impact Factor
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    ABSTRACT: To evaluate the performance of the American College of Cardiology/American Heart Association (ACC/AHA) 2013 Pooled Cohort Equations in the Korean Heart Study (KHS) population and to develop a Korean Risk Prediction Model (KRPM) for atherosclerotic cardiovascular disease (ASCVD) events. The KHS cohort included 200,010 Korean adults aged 40-79 years who were free from ASCVD at baseline. Discrimination, calibration, and recalibration of the ACC/AHA Equations in predicting 10-year ASCVD risk in the KHS cohort were evaluated. The KRPM was derived using Cox model coefficients, mean risk factor values, and mean incidences from the KHS cohort. In the discriminatory analysis, the ACC/AHA Equations' White and African-American (AA) models moderately distinguished cases from non-cases, and were similar to the KRPM: For men, the area under the receiver operating characteristic curve (AUROCs) were 0.727 (White model), 0.725 (AA model), and 0.741 (KRPM); for women, the corresponding AUROCs were 0.738, 0.739, and 0.745. Absolute 10-year ASCVD risk for men in the KHS cohort was overestimated by 56.5% (White model) and 74.1% (AA model), while the risk for women was underestimated by 27.9% (White model) and overestimated by 29.1% (AA model). Recalibration of the ACC/AHA Equations did not affect discriminatory ability but improved calibration substantially, especially in men in the White model. Of the three ASCVD risk prediction models, the KRPM showed best calibration. The ACC/AHA Equations should not be directly applied for ASCVD risk prediction in a Korean population. The KRPM showed best predictive ability for ASCVD risk. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Atherosclerosis 07/2015; 242(1):367-375. DOI:10.1016/j.atherosclerosis.2015.07.033 · 3.99 Impact Factor
  • Hee Tae Yu · Sungha Park · Eui-Cheol Shin · Won-Woo Lee ·
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    ABSTRACT: Age-related changes in the immune system, commonly termed "immunosenescence," contribute to deterioration of the immune response and fundamentally impact the health and survival of elderly individuals. Immunosenescence affects both the innate and adaptive immune systems; however, the most notable changes are in T cell immunity and include thymic involution, the collapse of T cell receptor (TCR) diversity, an imbalance in T cell populations, and the clonal expansion of senescent T cells. Senescent T cells have the ability to produce large quantities of proinflammatory cytokines and cytotoxic mediators; thus, they have been implicated in the pathogenesis of many chronic inflammatory diseases. Recently, an increasing body of evidence has suggested that senescent T cells also have pathogenic potential in cardiovascular diseases, such as hypertension, atherosclerosis, and myocardial infarction, underscoring the detrimental roles of these cells in various chronic inflammatory responses. Given that cardiovascular disease is the number one cause of death worldwide, there is great interest in understanding the contribution of age-related immunological changes to its pathogenesis. In this review, we discuss general features of age-related alterations in T cell immunity and the possible roles of senescent T cells in the pathogenesis of cardiovascular disease.
    Clinical and Experimental Medicine 07/2015; DOI:10.1007/s10238-015-0376-z · 2.96 Impact Factor
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    ABSTRACT: Arterial stiffness is an independent predictor of cardiovascular disease risk. However, whether genetic risk variants are associated with arterial stiffness measures, such as pulse-wave velocity (PWV), is largely unknown. Therefore, we performed a genome-wide association study (GWAS) to identify single-nucleotide polymorphisms (SNPs) associated with PWV in a Korea population. Study participants consisted of 402 patients in the Yonsei cardiovascular genome center cohort. Arterial stiffness was measured as brachial-ankle pulse-wave velocity (baPWV). Genotyping was performed in 402 subjects with the Axiom(™) Genome-Wide ASI 1 Array Plate containing more than 600,000 SNP markers. The findings were tested for replication in independent subjects from a community-based cohort of 1206 individuals, using a Taqman assay to include two candidate SNPs. Associations with PWV were evaluated using an additive genetic model that included age, gender, systolic blood pressure and diastolic blood pressure as covariates. GWAS and replication analyses were conducted using the measured genotype method implemented in PLINK and SAS. We observed two candidate SNPs associated with baPWV in GWAS: rs7271920 (p = 7.15 × 10(-9)) and rs10125157 (p = 8.25 × 10(-7)). However, neither of these was significant in the replication cohort. In summary, we did not identify any common genetic variants associated with baPWV in cardiovascular patients.
    Blood pressure 06/2015; 24(4). DOI:10.3109/08037051.2015.1049430 · 1.81 Impact Factor
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    ABSTRACT: Familial hypercholesterolemia (FH) is a genetic disorder with an increased risk of early-onset coronary artery disease. Although some clinically diagnosed FH cases are caused by mutations in LDLR, APOB, or PCSK9, mutation detection rates and profiles can vary across ethnic groups. In this study, we aimed to provide insight into the spectrum of FH-causing mutations in Koreans. Among 136 patients referred for FH, 69 who met Simon Broome criteria with definite family history were enrolled. By whole-exome sequencing (WES) analysis, we confirmed that the 3 known FH-related genes accounted for genetic causes in 23 patients (33.3%). A substantial portion of the mutations (19 of 23 patients, 82.6%) resulted from 17 mutations and 2 copy number deletions in LDLR gene. Two mutations each in the APOB and PCSK9 genes were verified. Of these anomalies, two frameshift deletions in LDLR and one mutation in PCSK9 were identified as novel causative mutations. In particular, one novel mutation and copy number deletion were validated by co-segregation in their relatives. This study confirmed the utility of genetic diagnosis of FH through WES.
    PLoS ONE 05/2015; 10(5):e0126706. DOI:10.1371/journal.pone.0126706 · 3.23 Impact Factor
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    ABSTRACT: Effects of peroxisome proliferator-activated receptor alpha (PPARα) agonists on cardiovascular outcome have been controversial. Although these agents primarily affect lipoprotein metabolism, their pleiotropic anti-inflammatory effect is one of the potential anti-atherosclerotic mechanisms. This study aimed to evaluate the effect of fenofibrate and gemfibrozil on inflammation in macrophages and reveal pathways these agents may affect. The two PPARα agonists inhibited secretion of CXCL2, TNF-α, IL-6, activation of p65 of NF-κB, ERK, and TLR4 expression. These changes occurred simultaneously with upregulation and secretion of β-defensin 1, an inflammation-modulating peptide. To demonstrate the role of β-defensin 1, it was knocked-down by target-specific siRNA. The effects of PPARα agonists on TLR4 expression and chemokine secretion were obviously abrogated with this treatment. In experiments investigating whether β-defensin 1 acts extracellularly, inflammatory chemokines decreased significantly after the addition of recombinant β-defensin 1 or conditioned media to cells. In experiments designed to clarify if the effects of the two agents are PPARα-dependent, induction of mRNA and secretion β-defensin 1 and inhibition of chemokine release were clearly reduced with GW6471, a PPARα blocker. Our results reveal the pathways by which fenofibrate and gemfibrozil inhibit LPS-induced inflammatory activation of macrophages. This study elucidated a novel anti-inflammatory mechanism that acts through PPARα, β-defensin 1, and TLR4 pathways. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Atherosclerosis 04/2015; 240(2). DOI:10.1016/j.atherosclerosis.2015.04.005 · 3.99 Impact Factor

  • Journal of the American Society of Hypertension 04/2015; 9(4):e43. DOI:10.1016/j.jash.2015.03.094 · 2.61 Impact Factor
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    ABSTRACT: The aim of this study was to determine the value of additional multiple biomarkers in the prediction of premature coronary artery disease (CAD). Data from 503 CAD patients and 503 healthy control patients with matching age and sex were collected. The patient group consisted of male (25 to 55 years) and female (30 to 60 years) patients with documented angiographic multi-vessel CAD. Baseline characteristics of conventional risk factors and biomarkers were collected. We compared the conventional risk factors model with the model with six additional biomarkers (hs-CRP, IL-6, RAGE, Lp-LPA2, adiponectin, and RANTES), which have shown significant association with premature CAD. We also evaluated the effects of adding each of the six biomarkers to the conventional laboratory data. The additional biomarkers model resulted in improvements in the C-statistic (0.953 vs. 0.937, P=0.0003) in comparison with the conventional risk factors model. Among the 6 biomarkers added to the patient group, hs-CRP and IL-6 had a significant discriminative power to predict the risk of premature CAD (hs-CRP; P = 0.0005, IL-6; P= 0.003). Although conventional risk factors were more strongly associated with premature CAD than were biomarkers, adding the 6 biomarkers (hs-CRP, IL-6, RAGE, Lp-LPA2, adiponectin, and RANTES) improved the prediction of premature CAD moderately. We found that hs-CRP and IL-6 had shown a significant contribution in the prediction of premature CAD.
    Acta cardiologica 04/2015; 70(2):205-10. DOI:10.2143/AC.70.2.3073512 · 0.65 Impact Factor
  • Yoon-Nyun Kim · Dong Gu Shin · Sungha Park · Chang Hee Lee ·
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    ABSTRACT: The effectiveness of remote patient monitoring and physician care for the treatment of hypertension has not been demonstrated in a randomized clinical trial. The objective of this study was to evaluate the effectiveness of remote patient monitoring with or without remote physician care in reducing office blood pressure in patients with hypertension. A total of 374 hypertensive patients over 20 years of age were randomized into the following three groups: group (1) control, the patients received usual clinical care with home BP monitoring; group (2) the patients were remotely monitored and received office follow-up; and group (3) the patients received remote monitoring without physician office care using the remote monitoring device. For each group, in-office follow-up care was scheduled every 8 weeks for 24 weeks. The primary end point was the difference in sitting SBP at the 24-week follow-up. No difference between the three groups was observed in the primary end point (adjusted mean sitting SBP was as follows: group 1: -8.9±15.5 mm Hg, group 2: -11.3±15.9 mm Hg, group 3: -11.6±19.8 mm Hg, (NS). Significant differences in achieving the target BP at the 24th week of follow-up were observed between groups 1 and 2. The subjects over 55-years old had a significant decrease in the adjusted mean sitting SBP in groups 2 and 3 compared with that of the control group. Remote monitoring alone or remote monitoring coupled with remote physician care was as efficacious as the usual office care for reducing blood pressure with comparable safety and efficacy in hypertensive patients.Hypertension Research advance online publication, 19 March 2015; doi:10.1038/hr.2015.32.
    Hypertension Research 03/2015; 38(7). DOI:10.1038/hr.2015.32 · 2.66 Impact Factor
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    ABSTRACT: T-cell-mediated immune responses play important roles in the progression of atherosclerotic disease. Studies have linked various inflammatory biomarkers with the burden of coronary artery calcification, but the significance of T-cell-specific chemokines in coronary artery calcification has not been confirmed. We aimed to examine the association between serum levels of the monokine induced by gamma interferon (MIG) and the coronary artery calcium score (CACS). We enrolled 456 individuals (285 men, 66.5±5.8 years) who were registered in the Mapo-gu public health center cohort. We selected 228 individuals with a CACS of more than 100 and 228 age-matched and sex-matched individuals with a CACS of less than 100. All participants underwent coronary computed tomography for CACS measuring. Clinical and laboratory variables including serum MIG levels were analyzed at the time of enrollment. The serum level of MIG was significantly higher in participants with a CACS of more than 100 (152.1±119.1 vs. 130.3±112.9, P=0.046). Serum MIG levels correlated significantly with CACS (r=0.113, P=0.016), and higher levels of MIG were associated with severe plaque burden (CACS>400, P=0.025). Multiple linear regression analysis showed that serum MIG levels were associated independently with CACS after controlling for confounding factors and medications (β=0.114, P=0.026). Serum MIG levels were associated independently with CACS after adjusting for traditional cardiovascular risk factors. These findings suggest that MIG may be used as a novel biomarker for T-cell inflammation and atherosclerotic plaque burden in humans.
    Coronary Artery Disease 03/2015; 26(4). DOI:10.1097/MCA.0000000000000236 · 1.50 Impact Factor

  • Journal of the American College of Cardiology 03/2015; 65(10):A1521. DOI:10.1016/S0735-1097(15)61521-2 · 16.50 Impact Factor

  • Journal of the American College of Cardiology 03/2015; 65(10):A1038. DOI:10.1016/S0735-1097(15)61038-5 · 16.50 Impact Factor

  • Journal of the American College of Cardiology 03/2015; 65(10):A989. DOI:10.1016/S0735-1097(15)60989-5 · 16.50 Impact Factor
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    Hee Tae Yu · Jeewon Lee · Eui-Cheol Shin · Sungha Park ·
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    ABSTRACT: Aim: The immune system may play an important role in the pathogenesis of cardiovascular disease. T cell-driven inflammation in human hypertension and atherosclerosis has recently been revealed. In the present study, we evaluated the association between serum levels of the C-X-C chemokine receptor type 3 chemokines and the carotid intima media thickness (IMT) in humans. Methods: One hundred sixty-four consecutive patients undergoing baseline and 2-year follow-up carotid IMT (110 men, 62.4±10.0 years) were enrolled. The maximum carotid IMT (max-IMT) and the mean carotid IMT (mean-IMT) were measured at baseline and after 24 months. Clinical and laboratory variables, including serum levels of the monokine induced by gamma interferon (MIG) and interferon gamma-induced protein 10 (IP-10), were analyzed at the time of initial enrollment. Results: The baseline max- and mean-IMT were 0.992±0.235 and 0.793±0.191 mm, respectively. The serum levels of MIG and IP-10 significantly correlated with the carotid IMT. However, there was no significant correlation between the serum levels of MIG or IP-10 and IMT changes. A multivariate regression analysis revealed the serum MIG to be independently associated with the carotid IMT (max-IMT: β=0.194, p=0.010; mean-IMT: β=0.184, p=0.016) when controlled for age, sex, diabetes mellitus history, smoking history, body mass index, blood pressure, total cholesterol, high-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and aspirin and statin medication. Conclusions: Circulating MIG levels are independently associated with the carotid IMT, after adjusting for confounding factors and medications. These findings indicate the potential clinical implication of MIG with respect to early atherosclerosis in humans.
    Journal of atherosclerosis and thrombosis 01/2015; 22(8). DOI:10.5551/jat.28886 · 2.73 Impact Factor
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    ABSTRACT: The activation of receptor for advanced glycation end products (RAGE) signaling is mainly associated with myocardial ischemia/reperfusion injury. Thus the blockade of RAGE-ligands axis can be considered as a potential therapeutic strategy to protect myocardial infarction after ischemia/reperfusion injury. Herein, we strengthened the cardioprotective effect with combinatorial treatment of soluble RAGE (sRAGE) and RAGE siRNA (siRAGE) causing more effective suppression of RAGE-mediated signaling transduction. For pharmacological blockade of RAGE, sRAGE, the extracellular ligand binding domain of RAGE, acts as a pharmacological ligand decoy and inhibits the interaction between RAGE and its ligands. For genetic deletion of RAGE, siRAGE suppresses the expression of RAGE by participating in RNA interference mechanism. Therefore, we combined these two RAGE blockade/deletion strategies and investigated the therapeutic effects on rat ischemic and reperfused myocardium. According to our results, based on RAGE expression level analysis and infarct size/fibrosis measurement, co-treatment of sRAGE and siRAGE exhibited synergic cardioprotective effects; thus the newly designed regimen can be considered as a promising candidate for the treatment of myocardial infarction.
    Archives of Pharmacal Research 01/2015; 38(7). DOI:10.1007/s12272-014-0527-x · 2.05 Impact Factor
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    ABSTRACT: The aim of this study was to investigate the status of LDL-cholesterol level and its relationship with subsequent cardiovascular events in Korean patients with chronic stable angina.
    01/2015; 4(1):27. DOI:10.12997/jla.2015.4.1.27

Publication Stats

2k Citations
555.97 Total Impact Points


  • 2015
    • University of Seoul
      Sŏul, Seoul, South Korea
  • 2007-2015
    • Yonsei University
      • • College of Medicine
      • • Department of Internal Medicine
      Sŏul, Seoul, South Korea
  • 2003-2015
    • Yonsei University Hospital
      • Department of Internal Medicine
      Sŏul, Seoul, South Korea
  • 2011-2013
    • Wonju Severance Christian Hospital
      Genshū, Gangwon-do, South Korea
  • 2009-2013
    • National Institute on Aging
      • Laboratory of Cardiovascular Science (LCS)
      Baltimore, Maryland, United States
    • Yonsei Proteome Research Center
      Sŏul, Seoul, South Korea
  • 2005
    • Hallym University Medical Center
      • Department of Internal Medicine
      Seoul, Seoul, South Korea