Myocardial insufficiency is related to reduced subunit 4 content of cytochrome c oxidase
Abstract Background Treatment of heart failure remains one of the most challenging task for intensive care medicine, cardiology and cardiac surgery. New options and better indicators are always required. Understanding the basic mechanisms underlying heart failure promote the development of adjusted...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2018-09-01
|
| Series: | Journal of Cardiothoracic Surgery |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13019-018-0785-7 |
| _version_ | 1818134384574726144 |
|---|---|
| author | Sebastian Vogt Volker Ruppert Sabine Pankuweit Jürgen P. J. Paletta Annika Rhiel Petra Weber Marc Irqsusi Pia Cybulski Rabia Ramzan |
| author_facet | Sebastian Vogt Volker Ruppert Sabine Pankuweit Jürgen P. J. Paletta Annika Rhiel Petra Weber Marc Irqsusi Pia Cybulski Rabia Ramzan |
| author_sort | Sebastian Vogt |
| collection | DOAJ |
| description | Abstract Background Treatment of heart failure remains one of the most challenging task for intensive care medicine, cardiology and cardiac surgery. New options and better indicators are always required. Understanding the basic mechanisms underlying heart failure promote the development of adjusted therapy e.g. assist devices and monitoring of recovery. If cardiac failure is related to compromised cellular respiration of the heart, remains unclear. Myocardial respiration depends on Cytochrome c- Oxidase (CytOx) activity representing the rate limiting step for the mitochondrial respiratory chain. The enzymatic activity as well as mRNA expression of enzyme’s mitochondrial encoded catalytic subunit 2, nuclear encoded regulatory subunit 4 and protein contents were studied in biopsies of cardiac patients suffering from myocardial insufficiency and dilated cardiomyopathy (DCM). Methods Fifty-four patients were enrolled in the study and underwent coronary angiography. Thirty male patients (mean age: 45 +/− 15 yrs.) had a reduced ejection fraction (EF) 35 ± 12% below 45% and a left ventricular end diastolic diameter (LVEDD) of 71 ± 10 mm bigger than 56 mm. They were diagnosed as having idiopathic dilated cardiomyopathy (DCM) without coronary heart disease and NYHA-class 3 and 4. Additionally, 24 male patients (mean age: 52 +/− 11 yrs.) after exclusion of secondary cardiomyopathies, coronary artery or valve disease, served as control (EF: 68 ± 7, LVEDD: 51 ± 7 mm). Total RNA was extracted from two biopsies of each person. Real-time PCR analysis was performed with specific primers followed by a melt curve analysis. Corresponding protein expression in the tissue was studied with immune-histochemistry while enzymatic activity was evaluated by spectroscopy. Results Gene and protein expression analysis of patients showed a significant decrease of subunit 4 (1.1 vs. 0.6, p < 0.001; 7.7 ± 3.1% vs. 2.8 ± 1.4%, p < 0.0001) but no differences in subunit 2. Correlations were found between reduced subunit 2 expression, low EF (r = 0.766, p < 0.00045) and increased LVEDD (r = 0.492, p < 0.0068). In case of DCM less subunit 4 expression and reduced shortening fraction (r = 0.524, p < 0.017) was found, but enzymatic activity was higher (0.08 ± 0.06 vs. 0.26 ± 0.08 U/mg, p < 0.001) although myocardial oxygen consumption continued to the same extent. Conclusion In case of myocardial insufficiency and DCM, decreased expression of COX 4 results in an impaired CytOx activity. Higher enzymatic activity but equal oxygen consumption contribute to the pathophysiology of the myocardial insufficiency and appears as an indicator of oxidative stress. This kind of dysregulation should be in the focus for the development of diagnostic and therapy procedures. |
| first_indexed | 2024-12-11T09:07:46Z |
| format | Article |
| id | doaj.art-79756cc07f974252a9b39c39f3e9ff0a |
| institution | Directory Open Access Journal |
| issn | 1749-8090 |
| language | English |
| last_indexed | 2024-12-11T09:07:46Z |
| publishDate | 2018-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Cardiothoracic Surgery |
| spelling | doaj.art-79756cc07f974252a9b39c39f3e9ff0a2022-12-22T01:13:34ZengBMCJournal of Cardiothoracic Surgery1749-80902018-09-011311910.1186/s13019-018-0785-7Myocardial insufficiency is related to reduced subunit 4 content of cytochrome c oxidaseSebastian Vogt0Volker Ruppert1Sabine Pankuweit2Jürgen P. J. Paletta3Annika Rhiel4Petra Weber5Marc Irqsusi6Pia Cybulski7Rabia Ramzan8Cardiovascular Research Laboratories at the Biochemical Pharmacological Center, Philipps-University Marburg and Universitätsklinikum Gießen and Marburg GmbHDepartment for Internal Medicine- Cardiology, Philipps-University Marburg and Universitätsklinikum Gießen and Marburg GmbHDepartment for Internal Medicine- Cardiology, Philipps-University Marburg and Universitätsklinikum Gießen and Marburg GmbHClinic for Orthopedics and Rheumatology, Philipps-University Marburg and Universitätsklinikum Gießen and Marburg GmbHCardiovascular Research Laboratories at the Biochemical Pharmacological Center, Philipps-University Marburg and Universitätsklinikum Gießen and Marburg GmbHCardiovascular Research Laboratories at the Biochemical Pharmacological Center, Philipps-University Marburg and Universitätsklinikum Gießen and Marburg GmbHHeart Surgery, Philipps-University Marburg and Universitätsklinikum Gießen and Marburg GmbHCardiovascular Research Laboratories at the Biochemical Pharmacological Center, Philipps-University Marburg and Universitätsklinikum Gießen and Marburg GmbHCardiovascular Research Laboratories at the Biochemical Pharmacological Center, Philipps-University Marburg and Universitätsklinikum Gießen and Marburg GmbHAbstract Background Treatment of heart failure remains one of the most challenging task for intensive care medicine, cardiology and cardiac surgery. New options and better indicators are always required. Understanding the basic mechanisms underlying heart failure promote the development of adjusted therapy e.g. assist devices and monitoring of recovery. If cardiac failure is related to compromised cellular respiration of the heart, remains unclear. Myocardial respiration depends on Cytochrome c- Oxidase (CytOx) activity representing the rate limiting step for the mitochondrial respiratory chain. The enzymatic activity as well as mRNA expression of enzyme’s mitochondrial encoded catalytic subunit 2, nuclear encoded regulatory subunit 4 and protein contents were studied in biopsies of cardiac patients suffering from myocardial insufficiency and dilated cardiomyopathy (DCM). Methods Fifty-four patients were enrolled in the study and underwent coronary angiography. Thirty male patients (mean age: 45 +/− 15 yrs.) had a reduced ejection fraction (EF) 35 ± 12% below 45% and a left ventricular end diastolic diameter (LVEDD) of 71 ± 10 mm bigger than 56 mm. They were diagnosed as having idiopathic dilated cardiomyopathy (DCM) without coronary heart disease and NYHA-class 3 and 4. Additionally, 24 male patients (mean age: 52 +/− 11 yrs.) after exclusion of secondary cardiomyopathies, coronary artery or valve disease, served as control (EF: 68 ± 7, LVEDD: 51 ± 7 mm). Total RNA was extracted from two biopsies of each person. Real-time PCR analysis was performed with specific primers followed by a melt curve analysis. Corresponding protein expression in the tissue was studied with immune-histochemistry while enzymatic activity was evaluated by spectroscopy. Results Gene and protein expression analysis of patients showed a significant decrease of subunit 4 (1.1 vs. 0.6, p < 0.001; 7.7 ± 3.1% vs. 2.8 ± 1.4%, p < 0.0001) but no differences in subunit 2. Correlations were found between reduced subunit 2 expression, low EF (r = 0.766, p < 0.00045) and increased LVEDD (r = 0.492, p < 0.0068). In case of DCM less subunit 4 expression and reduced shortening fraction (r = 0.524, p < 0.017) was found, but enzymatic activity was higher (0.08 ± 0.06 vs. 0.26 ± 0.08 U/mg, p < 0.001) although myocardial oxygen consumption continued to the same extent. Conclusion In case of myocardial insufficiency and DCM, decreased expression of COX 4 results in an impaired CytOx activity. Higher enzymatic activity but equal oxygen consumption contribute to the pathophysiology of the myocardial insufficiency and appears as an indicator of oxidative stress. This kind of dysregulation should be in the focus for the development of diagnostic and therapy procedures.http://link.springer.com/article/10.1186/s13019-018-0785-7Cytochrome c oxidaseMT –CO2 and COX 4 expressionMyocardial insufficiency |
| spellingShingle | Sebastian Vogt Volker Ruppert Sabine Pankuweit Jürgen P. J. Paletta Annika Rhiel Petra Weber Marc Irqsusi Pia Cybulski Rabia Ramzan Myocardial insufficiency is related to reduced subunit 4 content of cytochrome c oxidase Journal of Cardiothoracic Surgery Cytochrome c oxidase MT –CO2 and COX 4 expression Myocardial insufficiency |
| title | Myocardial insufficiency is related to reduced subunit 4 content of cytochrome c oxidase |
| title_full | Myocardial insufficiency is related to reduced subunit 4 content of cytochrome c oxidase |
| title_fullStr | Myocardial insufficiency is related to reduced subunit 4 content of cytochrome c oxidase |
| title_full_unstemmed | Myocardial insufficiency is related to reduced subunit 4 content of cytochrome c oxidase |
| title_short | Myocardial insufficiency is related to reduced subunit 4 content of cytochrome c oxidase |
| title_sort | myocardial insufficiency is related to reduced subunit 4 content of cytochrome c oxidase |
| topic | Cytochrome c oxidase MT –CO2 and COX 4 expression Myocardial insufficiency |
| url | http://link.springer.com/article/10.1186/s13019-018-0785-7 |
| work_keys_str_mv | AT sebastianvogt myocardialinsufficiencyisrelatedtoreducedsubunit4contentofcytochromecoxidase AT volkerruppert myocardialinsufficiencyisrelatedtoreducedsubunit4contentofcytochromecoxidase AT sabinepankuweit myocardialinsufficiencyisrelatedtoreducedsubunit4contentofcytochromecoxidase AT jurgenpjpaletta myocardialinsufficiencyisrelatedtoreducedsubunit4contentofcytochromecoxidase AT annikarhiel myocardialinsufficiencyisrelatedtoreducedsubunit4contentofcytochromecoxidase AT petraweber myocardialinsufficiencyisrelatedtoreducedsubunit4contentofcytochromecoxidase AT marcirqsusi myocardialinsufficiencyisrelatedtoreducedsubunit4contentofcytochromecoxidase AT piacybulski myocardialinsufficiencyisrelatedtoreducedsubunit4contentofcytochromecoxidase AT rabiaramzan myocardialinsufficiencyisrelatedtoreducedsubunit4contentofcytochromecoxidase |