Diverse Phenotypic Expression of Cardiomyopathies in a Family with TNNI3 p.Arg145Trp Mutation

황지원,장미애,장신이,서수현,성문우,박성섭,기창석,김덕경 대한심장학회 2017 Korean Circulation Journal Vol.47 No.2

Genetic diagnosis of cardiomyopathies (CMPs) is challenging, due to the marked genetic and allelic heterogeneity and the lack of knowledge of the mutations that lead to clinical phenotypes. Here, we present the case of a large family, in which a single troponin I type 3 (TNNI3) mutation caused variable phenotypic expression, ranging from restrictive cardiomyopathy (RCMP) to hypertrophic cardiomyopathy (HCMP) to near-normal phenotype. The proband was a 57-year-old female with HCMP. Examining the family history revealed that her elder sister had expired due to severe RCMP. Using a next-generation sequencing-based gene panel to analyze the proband, we identified a known TNNI3 gene mutation, c.433C>T, which is predicted to cause an amino acid substitution (p.Arg145Trp) in the highly conserved inhibitory region of the cardiac troponin I protein. Sanger sequencing confirmed that six relatives with RCMP or near-normal phenotypes also carried this mutation. To our knowledge, this is the first genetically confirmed family with diverse phenotypic expression of CMPs in Korea. Our findings demonstrate familial implications, where a single mutation in a sarcomere protein can cause diverse phenotypic expression of cardiomyopathies.

Original Article : Effects of aerobic exercise on antioxidants in rat models with cardiomyopathy

( Eun Jung Kim ),( Su Jin Hwang ) 물리치료재활과학회 2015 Physical therapy rehabilitation science Vol.4 No.1

Objective: In this study, we aimed to test the hypothesis that aerobic exercise might exert its cardio-protective effect by preventing oxidative stress and improving cardiac function in rat models with doxorubicin-induced cardiomyopathy. Design: Randomized controlled trial. Methods: We randomly divided experimental rats into four groups: the normal group was used as a non-cardiomyopathy normal control (n=10); the control group included non-aerobic exercise after doxorubicin-induced cardiomyopathy (n=10); the experimental group I included aerobic exercise (3 m/min) after doxorubicin-induced cardiomyopathy (n=10); and experimental group II included aerobic exercise (8 m/min) after doxorubicin-induced cardiomyopathy. Rats in the treadmill training groups underwent treadmill training, which began at 2 weeks after the first intraperitoneal injection. At the end of the exercise period, we determined the heart weight change for each rat. Changes in the levels of oxidative stress enzymes (superoxide dismutase [SOD], thiobarbituric acid-reactive substances [TBARS], and catalase) in the cardiac tissue of rats from all four groups were examined at the end of the experiment. Results: Significant cardiac myocyte injury and increase in myocardial TBARS concomitant with a reduction in myocardial SOD and catalase were observed following cardiomyopathy (p<0.05). Significant cardiac tissue and increase in myocardial TBARS along with reduction in myocardial SOD and catalase were observed following cardiomyopathy (p<0.05). Oxidative parameters were significantly improved in the aerobic exercise groups compared with the control group. Conclusions: These findings indicate that aerobic exercise effectively prevents oxidative stress in rat models with cardiomyopathy.

Carbon Monoxide Induced Cardiomyopathy: Epidemiology, Clinical Characteristics, and Prognosis

( Jung Hun Yoon ),( Ji Sook Lee ),( Yoon Seok Jung ),( Young Gi Min ),( Jin Seon Park ),( Woo Chan Jeon ),( Joon Han Shin ),( Sang Cheon Choi ) 대한응급의학회 2013 대한응급의학회 학술대회초록집 Vol.2013 No.2

Background: Some patients with acute carbon monoxide (CO) poisoning will experience cardiac failure. Although many previous reports demonstrated mechanisms of cardiac toxicity in acute CO poisoning, reports on epidemiology and clinical characteristics of CO induced cardiomyopathy have been limited and not elucidated. The aim of study was to investigate epidemiology, clinical characteristics, and prognosis of CO induced cardiomyopathy in patients with acute CO poisoning. Methods: A retrospective chart review was conducted on consecutive patients who visited to an emergency medical center, diagnosed as acute CO poisoning during a period of 62 months. A standardized extraction using medical records such as demographic, clinical, laboratory, and radiological data was performed on selected patients. The definition of CO induced CMP was as follows in the present study: 1) Transient hypokinesis, akinesia, or dyskinesis of the left ventricular midsegments with or without apical involvement after acute CO poisoning 2) the regional wall motion abnormalities extending beyond the geographic territory of a single epicardial artery, 3) absence of obstructive atherosclerotic coronary artery stenosis (<50% luminal narrowing of the epicardial artery), 4) New ECG abnormalities or modest elvevation in cardiac troponin. 5) complete recovery of regional wall motion abnormalities. Results: Among of 626 patients diagnosed as acute CO poisoning from July 2008 and August 2013, Echocardiography was performed on 84 patients: 65 patients were normal, and 19 patients were abnormal - global hypokinesia in 14 patients and any regional wall akinesia in 5 patients. In terms of ejection fraction, > EF 45% in 70 patients, < EF 45% in 14 patients. CO induced cardiomyopathy was identified in 19 patients. The gender ratio was 1: 0.73 (male: female), mean age was 42.6±21.1. At initial echocardiography, EF was 36.3± 13.5 (range 15% to 55%). Eleven patients underwent follow-up echocardiography had return to normal EF (≥ 50%), which was performed within 12 days from the time of initial echocardiography. Conclusion: CO induced cardiomyopathy was identified in 3.04% (n=19) of total patients (n=626) in the present study. When complete recovery from CO induced cardiomyopathy considered, the prognosis of CO induced cardiomyopathy was good. Therefore, the importance of CO induced cardiomyopathy was not significant by itself in clinical course of acute CO poisoning. Considering also the common denominators between Takotsubo cardiomyopathy and CO induced cardiomyopathy, we speculated that the injury mechanism of both diseases was seemed to be same as stunned myocardium due to catecholamine surge in myocardial synapses.

Effects of aerobic exercise on antioxidant in rat models with cardiomyopathy

김은정,황수진 물리치료재활과학회 2015 Physical therapy rehabilitation science Vol.4 No.1

Objective: In this study, we aimed to test the hypothesis that aerobic exercise might exert its cardio protective effect by preventing oxidative stress and improving cardiac function in a rat model of doxorubicin-induced cardiomyopathy. Design: Randomized controlled trial. Methods: We randomly divided experimental rats into four groups: the normal group was used as a non-cardiomyopathy normal control (n=10); the control group included non-aerobic exercise after doxorubicin-induced cardiomyopathy (n=10); the experimental group I included aerobic exercise (3 m/min) after doxorubicin-induced cardiomyopathy (n=10); and experimental group II included aerobic exercise (8 m/min) after doxorubicin-induced cardiomyopathy. Rats in the treadmill training groups underwent treadmill training, which began at 2 weeks after first intraperitoneal injection. At the end of the exercise period, we determined the heart weight change for each rat. Changes in the levels pf oxidative stress enzymes (SOD, TBARS, and catalase) in the cardiac tissue of rats from all four groups were examined at the end of the experiment. Results: Significant cardiac myocyte injury and increase in myocardial TBARS concomitant with a reduction in myocardial SOD and catalase were observed following cardiomyopathy. Oxidative parameters were significantly improved in the aerobic exercise groups compared with the control group. Conclusions: These findings indicate that aerobic exercise effectively prevents oxidative stress in a rat model of cardiomyopathy.

Effects of aerobic exercise on antioxidants in rat models with cardiomyopathy

Kim, Eun-Jung,Hwang, Sujin korean Academy of Physical Therapy Rehabilitation 2015 Physical therapy rehabilitation science Vol.4 No.1

Objective: In this study, we aimed to test the hypothesis that aerobic exercise might exert its cardio-protective effect by preventing oxidative stress and improving cardiac function in rat models with doxorubicin-induced cardiomyopathy. Design: Randomized controlled trial. Methods: We randomly divided experimental rats into four groups: the normal group was used as a non-cardiomyopathy normal control (n=10); the control group included non-aerobic exercise after doxorubicin-induced cardiomyopathy (n=10); the experimental group I included aerobic exercise (3 m/min) after doxorubicin-induced cardiomyopathy (n=10); and experimental group II included aerobic exercise (8 m/min) after doxorubicin-induced cardiomyopathy. Rats in the treadmill training groups underwent treadmill training, which began at 2 weeks after the first intraperitoneal injection. At the end of the exercise period, we determined the heart weight change for each rat. Changes in the levels of oxidative stress enzymes (superoxide dismutase [SOD], thiobarbituric acid-reactive substances [TBARS], and catalase) in the cardiac tissue of rats from all four groups were examined at the end of the experiment. Results: Significant cardiac myocyte injury and increase in myocardial TBARS concomitant with a reduction in myocardial SOD and catalase were observed following cardiomyopathy (p<0.05). Significant cardiac tissue and increase in myocardial TBARS along with reduction in myocardial SOD and catalase were observed following cardiomyopathy (p<0.05). Oxidative parameters were significantly improved in the aerobic exercise groups compared with the control group. Conclusions: These findings indicate that aerobic exercise effectively prevents oxidative stress in rat models with cardiomyopathy.

Recurrent Catecholamine-Induced Cardiomyopathy in a Patient With a Pheochromocytoma

장세영,양동헌,이상혁,김재희,박선희,조용근,채성철,전재은,박의현 대한심장학회 2009 Korean Circulation Journal Vol.39 No.6

Pheochromocytomas presents with variable clinical manifestations. Cardiomyopathy caused by a pheochromocytoma is well known. We report the case of a 62-year-old woman with recurrent left ventricular dysfunction, who was subsequently found to have a pheochromocytoma. The patient had two different patterns of cardiomyopathy. Patients with a cardiomyopathy, of non-specific origin, should have a pheochromocytoma ruled out. Pheochromocytomas presents with variable clinical manifestations. Cardiomyopathy caused by a pheochromocytoma is well known. We report the case of a 62-year-old woman with recurrent left ventricular dysfunction, who was subsequently found to have a pheochromocytoma. The patient had two different patterns of cardiomyopathy. Patients with a cardiomyopathy, of non-specific origin, should have a pheochromocytoma ruled out.

Diabetic Cardiomyopathy; Summary of 41 Years

Samet Yilmaz,Ugur Canpolat,Sinan Aydogdu,Hanna Emily Abboud 대한심장학회 2015 Korean Circulation Journal Vol.45 No.4

Patients with diabetes have an increased risk for development of cardiomyopathy, even in the absence of well known risk factors like coronary artery disease and hypertension. Diabetic cardiomyopathy was first recognized approximately four decades ago. To date, several pathophysiological mechanisms thought to be responsible for this new entity have also been recognized. In the presence of hyperglycemia, non-enzymatic glycosylation of several proteins, reactive oxygen species formation, and fibrosis lead to impairment of cardiac contractile functions. Impaired calcium handling, increased fatty acid oxidation, and increased neurohormonal activation also contribute to this process. Demonstration of left ventricular hypertrophy, early diastolic and late systolic dysfunction by sensitive techniques, help us to diagnose diabetic cardiomyopathy. Traditional treatment of heart failure is beneficial in diabetic cardiomyopathy, but specific strategies for prevention or treatment of cardiac dysfunction in diabetic patients has not been clarified yet. In this review we will discuss clinical and experimental studies focused on pathophysiology of diabetic cardiomyopathy, and summarize diagnostic and therapeutic approaches developed towards this entity.

Role of Autophagy in Granulocyte-Colony Stimulating Factor Induced Anti-Apoptotic Effects in Diabetic Cardiomyopathy

SHENGUANGYIN,신정훈,송이선,주현우,박인화,성진희,신나경,이아현,조영종,이용구,임영효,김혁,김경수 대한당뇨병학회 2021 Diabetes and Metabolism Journal Vol.45 No.4

Background We previously, reported that granulocyte-colony stimulating factor (G-CSF) reduces cardiomyocyte apoptosis in diabetic cardiomyopathy. However, the underlying mechanisms are not yet fully understood. Therefore, we investigated whether the mechanisms underlying of the anti-apoptotic effects of G-CSF were associated with autophagy using a rat model of diabetic cardiomyopathy. Methods Diabetic cardiomyopathy was induced in rats through a high-fat diet combined with low-dose streptozotocin and the rats were then treated with G-CSF for 5 days. Rat H9c2 cardiac cells were cultured under high glucose conditions as an in vitro model of diabetic cardiomyopathy. The extent of apoptosis and protein levels related to autophagy (Beclin-1, microtubule-binding protein light chain 3 [LC3]-II/LC3-I ratio, and P62) were determined for both models. Autophagy determination was performed using an Autophagy Detection kit. Results G-CSF significantly reduced cardiomyocyte apoptosis in the diabetic myocardium in vivo and led to an increase in Beclin-1 level and the LC3-II/LC3-I ratio, and decreased P62 level. Similarly, G-CSF suppressed apoptosis, increased Beclin-1 level and LC3-II/LC3-I ratio, and decreased P62 level in high glucose-induced H9c2 cardiac cells in vitro. These effects of G-CSF were abrogated by 3-methyladenine, an autophagy inhibitor. In addition, G-CSF significantly increased autophagic flux in vitro. Conclusion Our results suggest that the anti-apoptotic effect of G-CSF might be significantly associated with the up-regulation of autophagy in diabetic cardiomyopathy.

The Significance of Ventricular Volume in the Evaluation of Secondary Cardiomyopathy at Autopsy

나주영,민병우,김영희,정승현,이영직,김형석,박종태 대한병리학회 2011 Journal of Pathology and Translational Medicine Vol.45 No.4

Background: The weight, shape and consistency of the heart, and the thickness of the ventricular wall are used as parameters for evaluating postmortem heart and diagnosing cardiomyopathy at autopsy. Methods: The weight and volume of the ventricles and the thickness of the left ventricular wall of 58 hearts were measured and analyzed. Results: In the group of dilated hearts, the ventricular weight, ventricular volume, ventricular volume/ventricular weight, and left ventricular volume/right ventricular volume increased, whereas ventricular wall thickness decreased. In the group of hypertrophied hearts, the ventricular weight, ventricular volume, and thickness of the ventricular wall increased but ventricular volume/ventricular weight and left ventricular volume/right ventricular volume did not change significantly. In the group of undetermined hearts, it was later found that four of the cases should have been included in the dilated heart group and another two cases in the hypertrophied heart group. Conclusions: In addition to conventional methods, the measuring ventricular volume is useful for evaluating a postmortem heart and may suggest postmortem differential diagnoses of dilated or hypertrophied forms of secondary cardiomyopathies.

Doxorubicin 유발 심근증 백서 모델에서 성체골수줄기세포를 이용한 심근재생 효과

양관모,박찬석,장성원,박훈준,김동빈,김범준,정해억,백상홍,승기배,최규보 대한심장학회 2008 Korean Circulation Journal Vol.38 No.2

Background and Objectives: Bone marrow cells have been shown to differentiate into various cell lineages, including cardiomyocytes, in recent studies. This study evaluates the hypothesis that intravenous injection of bone marrow mononuclear cells (BMNCs) into rats with doxorubicin-induced cardiomyopathy can induce myocardial regeneration and improve myocardial contractility. Materials and Methods: Adult male Sprague-Dawley rats were induced to develop cardiomyopathy by treatment with doxorubicin (2.5 mg/kg, 6 times, 2-week period). Stem cell enriched BMNCs were injected into the tail vein of the rats after cessation of the doxorubicin injections. One week after the injection of PKH-67-labeled BMNCs, the localization of transplanted cells was evaluated. Immunohistochemical studies and Western blots were performed two weeks after BMNCs injection. Results: Cell-treated animals showed significant improvement in left ventricular fractional shortening as compared to untreated (control) rats (cell treated group vs. control group 47.2±4.9% vs. 34.4±3.6%, p<0.01). Histological analyses showed that in the cell-treated animals there was an increase in ventricular interstitial collagen deposition and the cell-treated animals had an improved number of capillary endothelial cells as compared with the control rats. PKH-67- labeled BMNCs and cell proliferation by BrdU was noted in the cell-treated hearts. Cardiac CXCR4 protein expression increased at day 7 and 14 in the cell-treated rats, but only at day 14 in the control animals. Conclusion: These results suggest that intravenous injection of BMNCs effectively induce engraftment of BMNCs into the myocardium and attenuation of fibrosis. Intravenous injection of BMNCs also improved myocardial contractility in doxorubicininduced cardiomyopathy. Background and Objectives: Bone marrow cells have been shown to differentiate into various cell lineages, including cardiomyocytes, in recent studies. This study evaluates the hypothesis that intravenous injection of bone marrow mononuclear cells (BMNCs) into rats with doxorubicin-induced cardiomyopathy can induce myocardial regeneration and improve myocardial contractility. Materials and Methods: Adult male Sprague-Dawley rats were induced to develop cardiomyopathy by treatment with doxorubicin (2.5 mg/kg, 6 times, 2-week period). Stem cell enriched BMNCs were injected into the tail vein of the rats after cessation of the doxorubicin injections. One week after the injection of PKH-67-labeled BMNCs, the localization of transplanted cells was evaluated. Immunohistochemical studies and Western blots were performed two weeks after BMNCs injection. Results: Cell-treated animals showed significant improvement in left ventricular fractional shortening as compared to untreated (control) rats (cell treated group vs. control group 47.2±4.9% vs. 34.4±3.6%, p<0.01). Histological analyses showed that in the cell-treated animals there was an increase in ventricular interstitial collagen deposition and the cell-treated animals had an improved number of capillary endothelial cells as compared with the control rats. PKH-67- labeled BMNCs and cell proliferation by BrdU was noted in the cell-treated hearts. Cardiac CXCR4 protein expression increased at day 7 and 14 in the cell-treated rats, but only at day 14 in the control animals. Conclusion: These results suggest that intravenous injection of BMNCs effectively induce engraftment of BMNCs into the myocardium and attenuation of fibrosis. Intravenous injection of BMNCs also improved myocardial contractility in doxorubicininduced cardiomyopathy.