Hye-Sun Seo

Tissue Transglutaminase Is Essential for Integrin-Mediated Survival of Bone Marrow-Derived Mesenchymal Stem Cells

Autologous mesenchymal stem cell (MSC) transplantation therapy for repair of myocardial injury has inherent limitations due to the poor viability of the stem cells after cell transplantation. Adhesion is a prerequisite for cell survival and also a key factor for the differentiation of MSCs. As a novel prosurvival modification strategy, we genetically engineered MSCs to overexpress tissue transglutaminase (tTG), with intention to enhance adhesion and ultimately cell survival after implantation. tTG‐transfected MSCs (tTG‐MSCs) showed a 2.7‐fold and greater than a twofold increase of tTG expression and surface tTG activity, respectively, leading to a 20% increased adhesion of MSCs on fibronectin (Fn). Spreading and migration of tTG‐MSCs were increased 4.75% and 2.52%, respectively. Adhesion of tTG‐MSCs on cardiogel, a cardiac fibroblast‐derived three‐dimensional matrix, showed a 33.1% increase. Downregulation of tTG by transfection of small interfering RNA specific to the tTG resulted in markedly decreased adhesion and spread of MSCs on Fn or cardiogel. tTG‐MSCs on Fn significantly increased phosphorylation of focal adhesion related kinases FAK, Src, and PI3K. tTG‐MSCs showed significant retention in infarcted myocardium by forming a focal adhesion complex and developed into cardiac myocyte‐like cells by the expression of cardiac‐specific proteins. Transplantation of 1 × 106 MSCs transduced with tTG into the ischemic rat myocardium restored normalized systolic and diastolic cardiac function. tTG‐MSCs further restored cardiac function of infarcted myocardium as compared with MSC transplantation alone. These findings suggested that tTG may play an important role in integrin‐mediated adhesion of MSCs in implanted tissues.

The prevalence and clinical predictors of atherosclerotic renal artery stenosis in patients undergoing coronary angiography

Renal artery stenosis is an important cause of secondary hypertension as well as ischemic nephropathy. The purpose of this study was to determine the clinical predictors in patients with renal artery stenosis in a population referred for coronary angiography. From March 1998 to July 1999, 1459 patients undergoing coronary angiography for various indications were routinely screened for renal artery stenosis by undergoing abdominal aortography. Coronary angiography, carotid angiography, and abdominal aortography was performed via either the radial or the femoral approach. The data were analyzed retrospectively. Out of 1459 patients undergoing abdominal aortography, 158 (10.8%) were found to have significant renal artery stenosis with 24 of the patients having bilateral stenosis. Significant coronary artery diseases were found in 994 of the 1459 study population (68.1%), with 134 (13.5%) of these patients having concomitant renal artery stenosis. Multivariate logistic regression showed that extracranial carotid artery stenosis odds ratio [(OR) 4.89 (95% confidence interval 2.57–9.33), P < 0.001], peripheral artery disease [OR 4.64 (2.65–9.33), P < 0.001], renal insufficiency [OR 2.68 (1.43–5.02), P = 0.002], significant coronary artery disease [OR 2.01 (1.12–3.59), P = 0.019], hypercholesterolemia [OR 1.92 (1.07–3.43), P = 0.028], hypertension [OR 1.85 (1.16–2.95), P = 0.010], and old age (>60 years) [OR 1.64 (1.01–2.64), P = 0.044] were significant clinical predictors of renovascular disease. The prevalence of indolent atherosclerotic renal artery stenosis is relatively high in selected groups of patients with high clincial risk factors for this underdiagnosed disease. Renal artery stenosis should be highly suspected in patients who have these risk factors because early detection of this disease may reverse the progression to chronic renal failure and end-stage renal disease.

Insulin resistance is associated with arterial stiffness in nondiabetic hypertensives independent of metabolic status.

We sought to determine whether insulin resistance (IR) is related to arterial stiffness in nondiabetic hypertensive patients, independent of metabolic status and gender. IR has been associated with increased arterial stiffness in patients with diabetes. In nondiabetic hypertensive patients, the correlation between IR and arterial stiffness has yet to be investigated. We enrolled 284 nondiabetic patients who were being treated for hypertension. At the time of enrollment, the patients underwent a baseline laboratory assessment including homeostatic model assessment (HOMA) IR index and pulse wave velocity (PWV). The HOMA IR index is used as a marker of IR, and brachial to ankle PWV (baPWV) was used as a marker of arterial stiffness. Of the 284 study subjects, 121 were classified as having metabolic syndrome. The patients with metabolic syndrome were older than the non-metabolic syndrome patients (55.4±10.7 vs. 52.1±11.6 years, p=0.013), but there was no gender difference between the two groups. The average baPWV was significantly higher in the patients with metabolic syndrome (1,506±235 vs. 1,435±211 cm/s, p=0.009). The HOMA index was independently associated with an increase in arterial stiffness (r=0.548, p<0.001) after controlling for age, systolic blood pressure (SBP), heart rate, medication and gender. The independent association of HOMA with arterial stiffness was demonstrated in subgroup analysis, regardless of the metabolic status and gender. In conclusion, increased IR was associated with arterial stiffness, independent of age, baseline SBP, gender and heart rate. This independent association of IR was demonstrated regardless of gender and metabolic status.

Noncompaction of the ventricular myocardium combined with polycystic kidney disease

Noncompaction of the ventricular myocardium (NVM) is a rare cardiac abnormality of unknown etiology. The condition is characterized by prominent and excessive trabeculations in a ventricular wall segment, with deep intertrabecular spaces perfused from the ventricular cavity. Polycystic kidney diseases are characterized by the formation of multiple cysts in the kidneys and liver and, less frequently, in the pancreas. Cardiovascular abnormalities including hypertension, mitral valve prolapse, and intracranial aneurysms are also frequently recognized. However, polycystic kidney disease and isolated ventricular noncompaction have not previously been correlated. Here, we describe one case of isolated noncompaction of ventricular myocardium with polycystic kidney disease, coupled with a progressive worsening of heart failure. We confirmed these abnormalities using contrast echocardiography, abdominopelvic computed tomography, and cardiac magnetic resonance imaging.

The Clinical Impact of Bedside Contrast Echocardiography in Intensive Care Settings: A Korean Multicenter Study

Background and Objectives We assessed the ability of portable echocardiography (with contrasts) to clearly delineate the cardiac structure, and evaluated the impact of its use on the diagnosis and management of critically ill patients in Korea. Subjects and Methods We prospectively enrolled 123 patients (mean age 66±16 years), who underwent portable transthoracic echocardiography (with contrast) for image enhancement at 12 medical centers. The quality of the global left ventricular (LV) images, the number of the regional LV segments visualized, the ability to visualize the LV apex and the right ventricle (RV), and any changes in the diagnostic procedure and treatment strategy were compared before and after the contrast. Results Of the 123 patients, 52 (42%) were using mechanical ventilators. The amount of poor or uninterpretable images decreased from 48% to 5% (p<0.001), after the contrast. Before the contrast, 15.6±1.1 of 16 LV segments were seen, which improved to 15.9±0.6 segments (p=0.001) after the contrast. The ability to visualize the LV apex increased from 47% to 94% (p<0.001), while the inability to clearly visualize the RV decreased from 46% to 19% (p<0.001). Changes in the diagnostic procedure (for example, not requiring other types of imaging studies) were observed in 18% of the patients, and the treatment plan (medication) was altered in 26% of patients after the contrast echocardiography. Conclusion The use of a contrast agent during the portable echocardiography, in intensive care settings, can improve the image quality and impact the diagnostic procedures and treatment for Korean patients.

2-Dimensional Strain Analysis of Regional Change in Right Ventricular Function after Treadmill Exercise

Background Function of right ventricle (RV) influences on symptoms and prognosis in various diseases. However the regional RV function analyzed with 2-dimensional (2D) strain echocardiography before and just after treadmill test has not been evaluated. The aim of this study was to show the change of regional RV function just after treadmill exercise with strain analysis. Methods A total of thirty eight patients who visited hospital for hypertension, chest pain or dyspnea between January 2007 and December 2010 were retrospectively analyzed (men, 47.4%; mean age, 54.9 ± 7.2 years). Treadmill exercise test and pre and post echocardiography were performed. 2D strain echocardiography was analyzed off line in RV free wall and septum. Results Mean exercise duration was 737 ± 132 sec. Tissue velocity in lateral tricuspid annulus is significantly increased in post exercise (initial, 10.5 ± 2.4 cm/sec vs. post exercise, 12.2 ± 1.8 cm/sec, p = 0.006). Systolic strain of RV free wall apex and mid portion were significantly changed in post exercise stage (free wall apex, -18.2 ± 7.6% vs. -22.3 ± 5.8%, p = 0.010; free wall mid, -14.1 ± 6.7% vs. -22.6 ± 6.8%, p = 0.022). Conclusion 2D strain imaging provides a precise tool to quantify regional RV function and reveals a characteristic regional pattern of RV after treadmill exercise.

Impact of Contrast Echocardiography on Assessment of Ventricular Function and Clinical Diagnosis in Routine Clinical Echocardiography: Korean Multicenter Study

Background Fundamental echocardiography has some drawbacks in patients with difficult-to-image echocardiograms. The aim of this study is to evaluate impact of contrast echocardiography (CE) on ventricular function assessment and clinical diagnosis in routine clinical echocardiography. Methods Two hundred sixty patients were prospectively enrolled over 3 years in 12 medical centers in Korea. General image quality, the number of distinguishable segments, ability to assess regional wall motion, left ventricular (LV) apex and right ventricle (RV) visualization, LV ejection fraction, changes in diagnostic or treatment plan were documented after echocardiography with and without ultrasound contrast agent. Results Poor or uninterpretable general image was 31% before contrast use, and decreased to 2% (p<0.05) after contrast use. The average number of visualized LV segments was 9.53 before contrast use, and increased to 14.46 (p<0.001) after contrast use. The percentage of poor or not seen LV regional wall motion was decreased from 28.4% to 3.5% (p<0.001). The percentage of poor or not seen LV apex and RV was decreased from 49.4% to 2.4% (p<0.001), from 30.5% to 10.5% (p<0.001), respectively. Changes in diagnostic procedure and treatment plan after CE were 30% and 29.6%, respectively. Conclusion Compared to fundamental echocardiography, CE impacted LV function assessment and clinical decision making in Korean patients who undergo routine echocardiography.

The image of submitral aneurysm with multiple fistulas.

A 64-year-old woman was admitted due to exertional dyspnoea (New York Heart Association functional class III) and pitting oedema. She had a past medical history of hypertension 4 years ago and hypercholesterolaemia 3 years ago. Her electrocardiogram showed normal sinus rhythm with enlargement of left atrium (LA). The echocardiogram showed …

A Case of Sheathless Transradial Coronary Intervention for Complex Coronary Lesions with a Standard Guiding Catheter

One of the major limitations of transradial coronary intervention is the inability to use large guiding system, which leads to the development of dedicated sheathless guide catheter system. However, these devices are not available in the Republic of Korea. We present a case in which conventional guiding catheter was used for sheathless transradial coronary intervention in the treatment of complex coronary anatomy.

An Unusual Type of Hypertrophic Cardiomyopathy

An unusual type of hypertrophic cardiomyopathy was diagnosed in a 17-year-old girl who presented with dyspnea on exertion. The hypertrophied myocardium was localized to the anterior portion of the left ventricle from the base to the apex without left ventricular outflow tract obstruction. On cardiac magnetic resonance imaging (MRI), patchy and linear delayed hyperenhancement was shown in the anterior and inferior mid-wall, which is not concordant with the coronary artery territory.