• Korean Journal of Radiology
• /
• 제21권6호
• /
• pp.717-725
• /
• 2020

Objective: To assess left ventricular remodeling patterns using cardiac computed tomography (CT) in children with congenital heart disease and correlate these patterns with their clinical course. Materials and Methods: Left ventricular volume and myocardial mass were quantified in 17 children with congenital heart disease who underwent initial and follow-up end-systolic cardiac CT studies with a mean follow-up duration of 8.4 ± 9.7 months. Based on changes in the indexed left ventricular myocardial mass (LVMi) and left ventricular mass-volume ratio (LVMVR), left ventricular remodeling between the two serial cardiac CT examinations was categorized into one of four patterns: pattern 1, increased LVMi and increased LVMVR; pattern 2, decreased LVMi and decreased LVMVR; pattern 3, increased LVMi and decreased LVMVR; and pattern 4, decreased LVMi and increased LVMVR. Left ventricular remodeling patterns were correlated with unfavorable clinical courses. Results: Baseline LVMi and LVMVR were 65.1 ± 37.9 g/m² and 4.0 ± 3.2 g/mL, respectively. LVMi increased in 10 patients and decreased in seven patients. LVMVR increased in seven patients and decreased in 10 patients. Pattern 1 was observed in seven patients, pattern 2 in seven, and pattern 3 in three patients. Unfavorable events were observed in 29% (2/7) of patients with pattern 1 and 67% (2/3) of patients with pattern 3, but no such events occurred in pattern 2 during the follow-up period (4.4 ± 2.7 years). Conclusion: Left ventricular remodeling patterns can be characterized using cardiac CT in children with congenital heart disease and may be used to predict their clinical course.

• The Korean Journal of Physiology and Pharmacology
• /
• 제28권3호
• /
• pp.285-294
• /
• 2024

Myocardial infarction is one of the leading causes of mortality globally. Currently, the pleiotropic inflammatory cytokine interleukin-6 (IL-6) is considered to be intimately related to the severity of myocardial injury during myocardial infarction. Interventions targeting IL-6 are a promising therapeutic option for myocardial infarction, but the underlying molecular mechanisms are not well understood. Here, we report the novel role of IL-6 in regulating adverse cardiac remodeling mediated by fibroblasts in a mouse model of myocardial infarction. It was found that the elevated expression of IL-6 in myocardium and cardiac fibroblasts was observed after myocardial infarction. Further, fibroblast-specific knockdown of Il6 significantly attenuated cardiac fibrosis and adverse cardiac remodeling and preserved cardiac function induced by myocardial infarction. Mechanistically, the role of Il6 contributing to cardiac fibrosis depends on signal transduction and activation of transcription (STAT)3 signaling activation. Additionally, Stat3 binds to the Il11 promoter region and contributes to the increased expression of Il11, which exacerbates cardiac fibrosis. In conclusion, these results suggest a novel role for IL-6 derived from fibroblasts in mediating Stat3 activation and substantially augmented Il11 expression in promoting cardiac fibrosis, highlighting its potential as a therapeutic target for cardiac fibrosis.

• Journal of Chest Surgery
• /
• 제54권6호
• /
• pp.439-448
• /
• 2021

Remodeling is a commonly encountered term in the field of cardiothoracic surgery that is often used to describe various pathophysiological changes in the dimension, structure, and function of various cardiac chambers, including the aorta. Stanford type A or DeBakey type 1 aortic dissection (TAAD) is a perplexing pathologic condition that can present surgical teams with the need to navigate a maze of complex decision-making. Ascending or hemi-arch replacement leaves behind a significant amount of distal diseased aortic tissue, which might have a persistent false lumen or primary or secondary intimal tears (or communications between lumina), which can lead to dilatation of the aortic arch. Unfavorable aortic remodeling is a major cause of distal aortic deterioration after the index surgery. Cardiac surgeons are aware of post-surgical cardiac chamber remodeling, but the concept of distal aortic remodeling is still idealized. The contemporary literature from established aortic centers supports aggressive management of the residual aortic pathology during the index surgery, and with continuing technical advancements, endovascular stenting options are readily available for patients with TAAD or for complicated type B aortic dissection cases. This review discusses the pathophysiology and treatment options for favorable distal aortic remodeling, as well as its impact on mid- to long-term outcomes following TAAD repair.

• Journal of Chest Surgery
• /
• 제54권1호
• /
• pp.45-52
• /
• 2021

Background: Atrial septal defect (ASD) is the most common congenital heart disease. However, the details of cardiac chamber remodeling after surgery are not well known, although this is an important issue that should be analyzed to understand long-term outcomes. Methods: Between November 2017 and January 2019, cardiac magnetic resonance imaging was performed preoperatively, at a 1-month postoperative follow-up, and at a 1-year postoperative follow-up. Cardiac chamber volume, valve regurgitation volume, and ejection fraction were measured as functions of time. Results: Thirteen patients (10 men and 3 women) were included. The median age at surgery was 51.4 years. The preoperative median ratio of flow in the pulmonary and systemic circulation was 2.3. The preoperative mean right ventricular (RV) end-diastolic volume index (EDVi) and RV end-systolic volume index (ESVi) had significantly decreased at the 1-month postoperative follow-up (p<0.001, p=0.001, respectively). The decrease in the RVEDVi (p=0.085) and RVESVi (p=0.023) continued until the postoperative 1-year follow-up, although the rate of decrease was slower. Tricuspid valve regurgitation had also decreased at the 1-month postoperative follow-up (p=0.022), and continued to decrease at a reduced rate (p=0.129). Although the RVEDVi and RVESVi improved after ASD closure, the RV volume parameters were still larger than the left ventricular (LV) volume parameters at the 1-year follow-up (RVEDVi vs. LVEDVi: p=0.016; RVESVi vs. LVESVi: p=0.001). Conclusion: Cardiac remodeling after ASD closure is common and mainly occurs in the early postoperative period. However, complete normalization does not occur.

• Molecules and Cells
• /
• 제43권4호
• /
• pp.408-418
• /
• 2020

The sinus node (SN) is located at the apex of the cardiac conduction system, and SN dysfunction (SND)-characterized by electrical remodeling-is generally attributed to idiopathic fibrosis or ischemic injuries in the SN. SND is associated with increased risk of cardiovascular disorders, including syncope, heart failure, and atrial arrhythmias, particularly atrial fibrillation. One of the histological SND hallmarks is degenerative atrial remodeling that is associated with conduction abnormalities and increased right atrial refractoriness. Although SND is frequently accompanied by increased fibrosis in the right atrium (RA), its molecular basis still remains elusive. Therefore, we investigated whether SND can induce significant molecular changes that account for the structural remodeling of RA. Towards this, we employed a rabbit model of experimental SND, and then compared the genome-wide RNA expression profiles in RA between SND-induced rabbits and sham-operated controls to identify the differentially expressed transcripts. The accompanying gene enrichment analysis revealed extensive pro-fibrotic changes within 7 days after the SN ablation, including activation of transforming growth factor-β (TGF-β) signaling and alterations in the levels of extracellular matrix components and their regulators. Importantly, our findings suggest that periostin, a matricellular factor that regulates the development of cardiac tissue, might play a key role in mediating TGF-β-signaling-induced aberrant atrial remodeling. In conclusion, the present study provides valuable information regarding the molecular signatures underlying SND-induced atrial remodeling, and indicates that periostin can be potentially used in the diagnosis of fibroproliferative cardiac dysfunctions.

• Journal of Chest Surgery
• /
• 제49권6호
• /
• pp.489-492
• /
• 2016

The original valve-sparing procedures for aortic root aneurysms were remodeling and reimplantation of the aortic root. The remodeling technique provides more physiologic movement of the cusps within 3 reconstructed neo-sinuses, thus preserving root expansibility through the interleaflet triangles. However, the durability of remodeling has been a matter of concern due to the high rate of aortic insufficiency when annular dilation is not addressed. Therefore, a modified approach was developed, combining a physiologic remodeling of the root with a subvalvular annuloplasty. This case report highlights the first case of successful aortic root remodeling with external subvalvular ring annuloplasty in Korea.

• Korean Journal of Radiology
• /
• 제22권10호
• /
• pp.1619-1627
• /
• 2021

Objective: This study used cardiac magnetic resonance imaging (MRI) to compare the characteristics of left ventricular remodeling in patients with primary aldosteronism (PA) with those of patients with essential hypertension (EH) and healthy controls (HCs). Materials and Methods: This prospective study enrolled 35 patients with PA, in addition to 35 age- and sex-matched patients with EH, and 35 age- and sex-matched HCs, all of whom underwent comprehensive clinical and cardiac MRI examinations. The analysis of variance was used to detect the differences in the characteristics of left ventricular remodeling among the three groups. Univariable and multivariable linear regression analyses were used to determine the relationships between left ventricular remodeling and the physiological variables. Results: The left ventricular end-diastolic volume index (EDVi) (mean ± standard deviation [SD]: 85.1 ± 13.0 mL/m² for PA, 75.9 ± 14.3 mL/m² for EH, and 77.3 ± 12.8 mL/m² for HC; p = 0.010), left ventricular end-systolic volume index (ESVi) (mean ± SD: 35.2 ± 9.8 mL/m² for PA, 30.7 ± 8.1 mL/m² for EH, and 29.5 ± 7.0 mL/m² for HC; p = 0.013), left ventricular mass index (mean ± SD: 65.8 ± 16.5 g/m² for PA, 56.9 ± 12.1 g/m² for EH, and 44.1 ± 8.9 g/m² for HC; p < 0.001), and native T1 (mean ± SD: 1224 ± 39 ms for PA, 1201 ± 47 ms for EH, and 1200 ± 44 ms for HC; p = 0.041) values were higher in the PA group compared to the EH and HC groups. Multivariable linear regression demonstrated that log (plasma aldosterone-to-renin ratio) was independently correlated with EDVi and ESVi. Plasma aldosterone was independently correlated with native T1. Conclusion: Patients with PA showed a greater degree of ventricular hypertrophy and enlargement, as well as myocardial fibrosis, compared to those with EH. Cardiac MRI T1 mapping can detect left ventricular myocardial fibrosis in patients with PA.

• The Korean Journal of Physiology and Pharmacology
• /
• 제25권1호
• /
• pp.1-14
• /
• 2021

Cardiovascular disease (CVD) accounts for approximately 30% of all deaths worldwide and its prevalence is constantly increasing despite advancements in medical treatments. Cardiac remodeling and dysfunction are independent risk factors for CVD. Recent studies have demonstrated that cardiac structure and function are genetically influenced, suggesting that understanding the genetic basis for cardiac structure and function could provide new insights into developing novel therapeutic targets for CVD. Regular exercise has long been considered a robust nontherapeutic method of treating or preventing CVD. However, recent studies also indicate that there is inter-individual variation in response to exercise. Nevertheless, the genetic basis for cardiac structure and function as well as their responses to exercise training have yet to be fully elucidated. Therefore, this review summarizes accumulated evidence supporting the genetic contribution to these traits, including findings from population-based studies and unbiased large genomic-scale studies in humans.

• Biomolecules & Therapeutics
• /
• 제21권5호
• /
• pp.371-380
• /
• 2013

Doxorubicin is still main drug in chemotherapy with limitation of use due to adverse drug reaction. Increased oxidative stress and alteration of nitric oxide control have been involved in cardiotoxicity of doxorubicin (DOX). A Disintegrin And Metalloproteinase (ADAMs) are transmembrane ectoproteases to regulate cell-cell and cell-matrix interactions, but role in cardiac disease is unclear. The aim of this study was to determine whether DOX activates peroxynitrite and ADAM 10 and thus ADAM and matrix metalloproteinase (MMP) induce cardiac remodeling in DOX-induced cardiomyopathy. Adult male Sprague-Dawley rats were subjected to cardiomyopathy by DOX (6 times of 2.5 mg/kg DOX over 2-weeks), and were randomized as four groups. Then followed by 3, 5, 7, and 14 days after cessation of DOX injection. DOX-injected animals significantly decreased left ventricular fractional shortening compared with control by M-mode echocardiography. The expressions of cardiac nitrotyrosine by immunohistochemistry were significant increased, and persisted for 2 weeks following the last injection. The expression of eNOS was increased by 1.9 times (p<0.05), and iNOS was marked increased in DOX-heart compared with control (p<0.001). Compared to control rats, cardiac ADAM10- and MMP 9- protein expressions increased by 20 times, and active/total MMP 9 proteolytic activity showed increase tendency at day 14 after cessation of DOX injection (n=10, each group). DOX-treated $H_9C_2$ cell showed increased ADAM10 protein expression with dose-dependency (p<0.01) and morphometric changes showed the increase of ventricular interstitial, nonvascular collagen deposition. These data suggest that activation of cardiac peroxynitrite with increased iNOS expression and ADAM 10-dependent MMP 9 expression may be a molecular mechanism that contributes to left ventricular remodeling in DOXinduced cardiomyopathy.

• The Korean Journal of Physiology and Pharmacology
• /
• 제19권3호
• /
• pp.203-210
• /
• 2015

AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism. Previous studies have shown that activation of AMPK results in suppression of cardiac myocyte hypertrophy via inhibition of the p70S6 kinase (p70S6K) and eukaryotic elongation factor-2 (eEF2) signaling pathways. Epigallocatechin-3-gallate (EGCG), the major polyphenol found in green tea, possesses multiple protective effects on the cardiovascular system including cardiac hypertrophy. However, the molecular mechanisms has not been well investigated. In this study, we found that EGCG could significantly reduce natriuretic peptides type A (Nppa), brain natriuretic polypeptide (BNP) mRNA expression and decrease cell surface area in H9C2 cardiomyocytes stimulated with phenylephrine (PE). Moreover, we showed that AMPK is activated in H9C2 cardiomyocytes by EGCG, and AMPK-dependent pathway participates in the inhibitory effects of EGCG on cardiac hypertrophy. Taken together, our findings provide the first evidence that the effect of EGCG against cardiac hypertrophy may be attributed to its activation on AMPK-dependent signaling pathway, suggesting the therapeutic potential of EGCG on the prevention of cardiac remodeling in patients with pressure overload hypertrophy.