1.Targeting SLC25A33 Suppresses Vascular Smooth Muscle Cell Proliferation and Migration by Reducing Cytosolic mtDNA Levels: Implications for Occlusive Vascular Diseases
Daehoon KIM ; Jieun SHIN ; Yeon-Kyung CHOI ; You Mie LEE ; Keun-Gyu PARK ; Hyang Sook KIM ; Jun-Kyu BYUN
Diabetes & Metabolism Journal 2026;50(1):139-152
Background:
Vascular smooth muscle cells (VSMCs) play a crucial role in the development of occlusive vascular diseases through abnormal proliferation and migration. This pathological behavior is closely associated with mitochondrial reactive oxygen species (ROS)-mediated mitochondrial DNA (mtDNA) damage. The mitochondrial carrier protein solute carrier family 25 member 33 (SLC25A33), essential for nucleoside transport, is integral to mtDNA production. This study aimed to investigate the effects of SLC25A33 inhibition on the proliferation and migration of VSMCs, as well as its impact on neointima formation.
Methods:
VSMCs were isolated from the thoracic aorta of 4-week-old Sprague-Dawley rats. The effects of small interfering RNAinduced silencing of SLC25A33 mRNA on platelet-derived growth factor (PDGF)-induced proliferation and migration of VSMCs were analyzed. The in vivo effects of targeting the SLC25A33 gene on neointima formation were evaluated using a murine carotid artery ligation model by perivascularly applying Lenti-shSLC25A33 with Pluronic F-127 gel.
Results:
First, we observed an upregulation of the SLC25A33 protein in the carotid artery ligation-induced neointima in mice. Silencing of SLC25A33 suppressed the PDGF-stimulated proliferation and migration of VSMCs and cell cycle progression. Knockdown of SLC25A33 inhibited PDGF-induced production of mtDNA and ROS, consequently inactivating the cyclic GMP-AMP synthesis (cGAS)-stimulator of interferon genes (STING)-TANK-binding kinase 1 (TBK1)-nuclear factor kappa B (NF-κB) pathway. Furthermore, the downregulation of SLC25A33 reduced carotid artery ligation-induced neointima in mice.
Conclusion
This study suggests that targeting SLC25A33 in VSMCs could be a novel therapeutic strategy to prevent occlusive vascular diseases.
2.Predicting the response to cardiac resynchronization therapy using in silico heart models: pilot study of comparison between in silico and real cardiac resynchronization therapy outcomes
Jae-Sun UHM ; Minki HWANG ; Eun Bo SHIM ; Daehoon KIM ; Chan Joo LEE ; Jaewon OH ; Hee Tae YU ; Tae-Hoon KIM ; Boyoung JOUNG ; Hui-Nam PAK ; Seok-Min KANG ; Moon-Hyoung LEE
International Journal of Arrhythmia 2025;26(1):e9-
Background and Objectives:
Cardiac resynchronization therapy (CRT) is a treatment option for patients with heart failure and left ventricular (LV) dyssynchrony. However, one-third of CRT patients are non-responders. The objective of this study is to evaluate the feasibility of an in silico electromechanical heart model to predict CRT outcomes.
Methods:
The three-dimensional heart geometries of 11 patients (age, 64.0 ± 10.7 years, 4 men) with CRT were constructed from cardiac computed tomography images. The finite element method was used to simulate the electrical wave propagation and mechanics in the heart. We coupled cardiac electrical excitation and mechanical contraction with vascular hemodynamics using a lumped parameter model. We predicted the LV end-diastolic and end-systolic volumes and LV ejection fraction (LVEF) after CRT implantation using the in silico CRT simulation model. A CRT responder was defined as a patient with an absolute LVEF increase ≥ 5%. We compared the in silico CRT outcomes with the real CRT outcomes.
Results:
Two patients were in silico CRT responders, and those 2 patients were also real CRT responders. Nine patients were in silico CRT non-responders, 8 who were real CRT non-responders, and 1 who was a real CRT responder. The in silico CRT outcomes agreed with the real CRT outcomes in 10 of 11 patients. The positive and negative predictive values, accuracy, sensitivity, and specificity of the in silico CRT model were 100%, 88.9%, 90.9%, 66.7%, and 100%, respectively.
Conclusion
The in silico CRT simulation model is feasible for predicting real CRT outcomes.
3.Reinforcing treatment and evaluation workflow of stereotactic ablative body radiotherapy for refractory ventricular tachycardia
Hojin KIM ; Sangjoon PARK ; Jihun KIM ; Jin Sung KIM ; Dong Wook KIM ; Nalee KIM ; Jae-Sun UHM ; Daehoon KIM ; Hui-Nam PAK ; Chae-Seon HONG ; Hong In YOON
Radiation Oncology Journal 2024;42(4):319-329
Purpose:
Cardiac radioablation is a novel, non-invasive treatment for ventricular tachycardia (VT), involving a single fractional stereotactic ablative body radiotherapy (SABR) session with a prescribed dose of 25 Gy. This complex procedure requires a detailed workflow and stringent dose constraints compared to conventional radiation therapy. This study aims to establish a consistent institutional workflow for single-fraction cardiac VT-SABR, emphasizing robust plan evaluation and quality assurance.
Materials and Methods:
The study developed a consistent institutional workflow for VT-SABR, including computed tomography (CT) simulation, target volume definition, treatment planning, robust plan evaluation, quality assurance, and image-guided strategy. The workflow was implemented for two patients with cardiac arrhythmia. Accurate target volume definition using planning CT images and electronic anatomical mapping was critical. A four-dimensional (4D) cone-beam CT (CBCT) and breath-hold electrocardiographic gated CT images reliably detected target motion.
Results:
The resulting plans exhibited a conformity index greater than 0.7 and a gradient index around G4.0. Dose constraints for the planning target volume (PTV) aimed for 95% or higher PTV dose coverage, with a maximum dose of 200% or lower. However, one case did not meet the PTV dose coverage due to the proximity of the PTV to gastrointestinal organs. Plans adhered to dose constraints for organs at risk near the heart, but meeting constraints for specific cardiac sub-structures was challenging and dependent on PTV location.
Conclusion
The plans demonstrated robustness against respiratory motion and patient positional uncertainty through a robust evaluation function. The 4D and intra-fractional CBCT were effective in verifying target motion and setup stability.
4.Reinforcing treatment and evaluation workflow of stereotactic ablative body radiotherapy for refractory ventricular tachycardia
Hojin KIM ; Sangjoon PARK ; Jihun KIM ; Jin Sung KIM ; Dong Wook KIM ; Nalee KIM ; Jae-Sun UHM ; Daehoon KIM ; Hui-Nam PAK ; Chae-Seon HONG ; Hong In YOON
Radiation Oncology Journal 2024;42(4):319-329
Purpose:
Cardiac radioablation is a novel, non-invasive treatment for ventricular tachycardia (VT), involving a single fractional stereotactic ablative body radiotherapy (SABR) session with a prescribed dose of 25 Gy. This complex procedure requires a detailed workflow and stringent dose constraints compared to conventional radiation therapy. This study aims to establish a consistent institutional workflow for single-fraction cardiac VT-SABR, emphasizing robust plan evaluation and quality assurance.
Materials and Methods:
The study developed a consistent institutional workflow for VT-SABR, including computed tomography (CT) simulation, target volume definition, treatment planning, robust plan evaluation, quality assurance, and image-guided strategy. The workflow was implemented for two patients with cardiac arrhythmia. Accurate target volume definition using planning CT images and electronic anatomical mapping was critical. A four-dimensional (4D) cone-beam CT (CBCT) and breath-hold electrocardiographic gated CT images reliably detected target motion.
Results:
The resulting plans exhibited a conformity index greater than 0.7 and a gradient index around G4.0. Dose constraints for the planning target volume (PTV) aimed for 95% or higher PTV dose coverage, with a maximum dose of 200% or lower. However, one case did not meet the PTV dose coverage due to the proximity of the PTV to gastrointestinal organs. Plans adhered to dose constraints for organs at risk near the heart, but meeting constraints for specific cardiac sub-structures was challenging and dependent on PTV location.
Conclusion
The plans demonstrated robustness against respiratory motion and patient positional uncertainty through a robust evaluation function. The 4D and intra-fractional CBCT were effective in verifying target motion and setup stability.
5.Reinforcing treatment and evaluation workflow of stereotactic ablative body radiotherapy for refractory ventricular tachycardia
Hojin KIM ; Sangjoon PARK ; Jihun KIM ; Jin Sung KIM ; Dong Wook KIM ; Nalee KIM ; Jae-Sun UHM ; Daehoon KIM ; Hui-Nam PAK ; Chae-Seon HONG ; Hong In YOON
Radiation Oncology Journal 2024;42(4):319-329
Purpose:
Cardiac radioablation is a novel, non-invasive treatment for ventricular tachycardia (VT), involving a single fractional stereotactic ablative body radiotherapy (SABR) session with a prescribed dose of 25 Gy. This complex procedure requires a detailed workflow and stringent dose constraints compared to conventional radiation therapy. This study aims to establish a consistent institutional workflow for single-fraction cardiac VT-SABR, emphasizing robust plan evaluation and quality assurance.
Materials and Methods:
The study developed a consistent institutional workflow for VT-SABR, including computed tomography (CT) simulation, target volume definition, treatment planning, robust plan evaluation, quality assurance, and image-guided strategy. The workflow was implemented for two patients with cardiac arrhythmia. Accurate target volume definition using planning CT images and electronic anatomical mapping was critical. A four-dimensional (4D) cone-beam CT (CBCT) and breath-hold electrocardiographic gated CT images reliably detected target motion.
Results:
The resulting plans exhibited a conformity index greater than 0.7 and a gradient index around G4.0. Dose constraints for the planning target volume (PTV) aimed for 95% or higher PTV dose coverage, with a maximum dose of 200% or lower. However, one case did not meet the PTV dose coverage due to the proximity of the PTV to gastrointestinal organs. Plans adhered to dose constraints for organs at risk near the heart, but meeting constraints for specific cardiac sub-structures was challenging and dependent on PTV location.
Conclusion
The plans demonstrated robustness against respiratory motion and patient positional uncertainty through a robust evaluation function. The 4D and intra-fractional CBCT were effective in verifying target motion and setup stability.
6.Reinforcing treatment and evaluation workflow of stereotactic ablative body radiotherapy for refractory ventricular tachycardia
Hojin KIM ; Sangjoon PARK ; Jihun KIM ; Jin Sung KIM ; Dong Wook KIM ; Nalee KIM ; Jae-Sun UHM ; Daehoon KIM ; Hui-Nam PAK ; Chae-Seon HONG ; Hong In YOON
Radiation Oncology Journal 2024;42(4):319-329
Purpose:
Cardiac radioablation is a novel, non-invasive treatment for ventricular tachycardia (VT), involving a single fractional stereotactic ablative body radiotherapy (SABR) session with a prescribed dose of 25 Gy. This complex procedure requires a detailed workflow and stringent dose constraints compared to conventional radiation therapy. This study aims to establish a consistent institutional workflow for single-fraction cardiac VT-SABR, emphasizing robust plan evaluation and quality assurance.
Materials and Methods:
The study developed a consistent institutional workflow for VT-SABR, including computed tomography (CT) simulation, target volume definition, treatment planning, robust plan evaluation, quality assurance, and image-guided strategy. The workflow was implemented for two patients with cardiac arrhythmia. Accurate target volume definition using planning CT images and electronic anatomical mapping was critical. A four-dimensional (4D) cone-beam CT (CBCT) and breath-hold electrocardiographic gated CT images reliably detected target motion.
Results:
The resulting plans exhibited a conformity index greater than 0.7 and a gradient index around G4.0. Dose constraints for the planning target volume (PTV) aimed for 95% or higher PTV dose coverage, with a maximum dose of 200% or lower. However, one case did not meet the PTV dose coverage due to the proximity of the PTV to gastrointestinal organs. Plans adhered to dose constraints for organs at risk near the heart, but meeting constraints for specific cardiac sub-structures was challenging and dependent on PTV location.
Conclusion
The plans demonstrated robustness against respiratory motion and patient positional uncertainty through a robust evaluation function. The 4D and intra-fractional CBCT were effective in verifying target motion and setup stability.
7.Association between Obesity and Heart Failure and Related Atrial Fibrillation: Patient-Level Data Comparisons of Two Cohort Studies
Young Shin LEE ; Pil-Sung YANG ; Eunsun JANG ; Daehoon KIM ; Hee Tae YU ; Tae-Hoon KIM ; Jae-Sun UHM ; Jung-Hoon SUNG ; Hui-Nam PAK ; Moon-Hyoung LEE ; Boyoung JOUNG
Yonsei Medical Journal 2024;65(1):10-18
Purpose:
Heart failure (HF) and atrial fibrillation (AF) frequently coexist, with over 50% patients with HF having AF, while onethird of those with AF develop HF. Differences in obesity-mediated association between HF and HF-related AF among Asians and Europeans were evaluated.
Materials and Methods:
Using the Korean National Health Insurance Service-Health Screening (K-NHIS-HealS) cohort and the UK Biobank, we included 394801 Korean and 476883 UK adults, respectively aged 40–70 years. The incidence and risk of HF were evaluated based on body mass index (BMI).
Results:
The proportion of obese individuals was significantly higher in the UK Biobank cohort than in the K-NHIS-HealS cohort (24.2% vs. 2.7%, p<0.001). The incidence of HF and HF-related AF was higher among the obese in the UK than in Korea. The risk of HF was higher among the British than in Koreans, with adjusted hazard ratios of 1.82 [95% confidence interval (CI), 1.30–2.55] in KNHIS-HealS and 2.00 (95% CI, 1.69–2.37) in UK Biobank in obese participants (p for interaction <0.001). A 5-unit increase in BMI was associated with a 44% greater risk of HF-related AF in the UK Biobank cohort (p<0.001) but not in the K-NHIS-HealS cohort (p=0.277).
Conclusion
Obesity was associated with an increased risk of HF and HF-related AF in both Korean and UK populations. The higher incidence in the UK population was likely due to the higher proportion of obese individuals.
8.Atrial fibrillation fact sheet in Korea 2024(part 1): epidemiology of atrial fibrillation in Korea
So‑Ryoung LEE ; Daehoon KIM ; Sung Ho LEE ; Woo‑Hyun LIM ; Kwang Jin CHUN ; Won‑Seok CHOE ; Hyo‑Jeong AHN ; Kyung‑Yeon LEE ; JungMin CHOI ; Bong‑Seong KIM ; Kyung‑Do HAN ; Eue‑Keun CHOI
International Journal of Arrhythmia 2024;25(3):13-
Background and objectives:
This study aimed to analyze and present updated trends in atrial fibrillation (AF) epidemiology within the Korean population, providing a foundation for planning and implementing appropriate management and treatment strategies for patients with AF.
Patients and methods:
We used the Korean National Health Insurance Service database to evaluate the prevalence, incidence, comorbidities, and clinical adverse outcomes of patients with AF in Korea between 2013 and 2022.
Results:
AF prevalence in Korean adults aged ≥ 20 years doubled (1.1 to 2.2%) between 2013 and 2022, with significant increases observed across various sex and age groups. Similarly, the number of newly diagnosed patients with AF per year increased steadily, with the incidence rising from 184 to 275 per 100,000 person-years, particularly among older populations. Over this period, the mean age of patients with AF increased from 67.7 to 70.3 years, and comorbidities prevalence and CHA2DS2-VASc score rose significantly, indicating a higher stroke risk. Compared with patients without AF, AF was associated with an increased risk of mortality (hazard ratio [HR]: 1.78), ischemic stroke (HR: 2.39), major bleeding (HR: 2.10), myocardial infarction (HR: 1.44), and heart failure admission (HR: 2.42).
Conclusion
AF prevalence and incidence have steadily increased between 2013 and 2022, with a more pronounced increase in older patients. Patients with AF are increasingly becoming a high-risk population and are at increased risk of clinical adverse outcomes compared to non-AF patients. Therefore, a sustained national effort to improve AF awareness and comprehensive care quality for patients with AF is required.
9.The Effects of Radiofrequency Catheter Ablation for Atrial Fibrillation on Right Ventricular Function
Minkwan KIM ; Jae-Sun UHM ; Je-Wook PARK ; SungA BAE ; In Hyun JUNG ; Seok-Jae HEO ; Daehoon KIM ; Hee Tae YU ; Tae-Hoon KIM ; Boyoung JOUNG ; Moon-Hyoung LEE
Korean Circulation Journal 2024;54(4):203-217
Background:
and Objective: The effects of radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) on right ventricular (RV) function are not well known.
Methods:
Patients who underwent RFCA for AF and underwent pre- and post-procedural echocardiography were enrolled consecutively. Fractional area change (FAC), RV free-wall longitudinal strain (RVFWSL), and RV 4-chamber strain including the ventricular septum (RV4CSL) were measured. Changes in FAC, RVFWSL, and RV4CSL before and after RFCA were compared among paroxysmal AF (PAF), persistent AF (PeAF), and long-standing persistent AF (LSPeAF) groups.
Results:
A total of 164 participants (74 PAF, 47 PeAF, and 43 LSPeAF; age, 60.8 ± 9.8 years;men, 74.4%) was enrolled. The patients with PeAF and LSPeAF had worse RV4CSL (p<0.001) and RVFWSL (p<0.001) than those with PAF and reference values. Improvements in RVFWSL and RV4CSL after RFCA were significant in the PeAF group compared with the PAF and LSPeAF groups (ΔRV4CSL, 8.4% [5.1, 11.6] in PeAF vs. 1.0% [−1.0, 4.1] in PAF, 1.9% [−0.2, 4.4] in LSPeAF, p<0.001; ΔRVFWSL, 9.0% [6.9, 11.5] in PeAF vs. 0.9% [−1.4, 4.9] in PAF, 1.0% [−1.0, 3.6] in LSPeAF, p<0.001). In patients without recurrence, improvements in RVFWSL and RV4CSL after RFCA were significant in the PeAF group compared to the LSPeAF group.
Conclusions
RV systolic function is more impaired in patients with PeAF and LSPeAF than in those with PAF. RV systolic function is more improved after RFCA in patients with PeAF than in those with PAF or LSPeAF.

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