Abstract:
:Impaired nitric oxide (NO)-soluble guanylate cyclase (sGC)-cGMP signaling is involved in the pathogenesis of ischemic heart diseases, yet the impact of long-term sGC activation on progressive cardiac remodeling and heart failure after myocardial infarction (MI) has not been explored. Moreover, it is unknown whether stimulating the NO/heme-independent sGC provides additional benefits to ACE inhibition in chronic ischemic heart failure. Starting 10 days after MI, rats were treated with placebo, the sGC activator ataciguat (10 mg/kg/twice daily), ramipril (1 mg/kg/day), or a combination of both for 9 weeks. Long-term ataciguat therapy reduced left ventricular (LV) diastolic filling pressure and pulmonary edema, improved the rightward shift of the pressure-volume curve, LV contractile function and diastolic stiffness, without lowering blood pressure. NO/heme-independent sGC activation provided protection over ACE inhibition against mitochondrial superoxide production and progressive fibrotic remodeling, ultimately leading to a further improvement of cardiac performance, hypertrophic growth and heart failure. We found that ataciguat stimulating sGC activity was potentiated in (myo)fibroblasts during hypoxia-induced oxidative stress and that NO/heme-independent sGC activation modulated fibroblast-cardiomyocyte crosstalk in the context of heart failure and hypoxia. In addition, ataciguat inhibited human cardiac fibroblast differentiation and extracellular matrix protein production in response to TGF-β1. Overall, long-term sGC activation targeting extracellular matrix homeostasis conferred cardioprotection against progressive cardiac dysfunction, pathological remodeling and heart failure after myocardial infarction. NO/heme-independent sGC activation may prove to be a useful therapeutic target in patients with chronic heart failure and ongoing fibrotic remodeling.
journal_name
Basic Res Cardioljournal_title
Basic research in cardiologyauthors
Fraccarollo D,Galuppo P,Motschenbacher S,Ruetten H,Schäfer A,Bauersachs Jdoi
10.1007/s00395-014-0421-1subject
Has Abstractpub_date
2014-07-01 00:00:00pages
421issue
4eissn
0300-8428issn
1435-1803journal_volume
109pub_type
杂志文章abstract::There is no doubt that major advances have been made in cardiac electrophysiology using single heart cells. Accurate analysis of rapid inward sodium current and the second inward current carried by calcium has resulted in a major re-examination of the steps involved in excitation-contraction coupling in the heart. Fut...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/978-3-662-11041-6_17
更新日期:1985-01-01 00:00:00
abstract::In the isometrically contracting rat trabecular muscle strip preparation, contracture tension was induced either by 10 min of hypoxia (low contracture tension) or by 30 min of joint oxygen and glucose withdrawal (severe contracture tension) at optimum length. Using stepwise 0.1 mm releases, length-tension relationship...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01908059
更新日期:1981-11-01 00:00:00
abstract::Two-weekly echocardiographic examinations were conducted in nine SHHF-Mc-fa(cp) rats in comparison with eight age-matched Wistar rats. In the SHHF-rats, characterized by progressive LV-dilation and decreasing contractile function between 77-87 weeks of age, left ventricular (LV) hypertrophy was most sensitively demons...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-003-0401-3
更新日期:2003-09-01 00:00:00
abstract::Elevation of cardiac troponin I (cTnI) is a well-known complication after percutaneous coronary interventions (PCI). The aims of this study were to quantify the extent of coronary microembolization during elective PCI, to identify predisposing anatomical and procedural factors, and to evaluate its impact on long-term ...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-012-0289-x
更新日期:2012-09-01 00:00:00
abstract::Hearts preconditioned by brief ischemia are characterized by a reduced rate of cellular purine metabolite production during subsequent prolonged ischemia; the purpose of this study was to determine if transient exogenous adenosine pretreatment can mimic this phenomenon. The accumulation of interstitial fluid (ISF) pur...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF00796210
更新日期:1997-12-01 00:00:00
abstract::Total global ischaemia of the normothermic working rat heart caused an initial positive inotropic response characterized by vigorous contractions. After +/- 15 s this response reached a peak whereafter the isotonic contraction amplitude started to decline. After +/- 3.5 min the heart ceased to beat. The low level of h...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01906862
更新日期:1987-05-01 00:00:00
abstract::Our understanding of what constitutes "normal" collagen organization in wound healing after myocardial injury and how such organization is achieved is still in its infancy. However, once this knowledge has been obtained, it may suggest methods of enhancing or even optimizing healing, and thus provide us with the possi...
journal_title:Basic research in cardiology
pub_type: 杂志文章,评审
doi:10.1007/s003950050201
更新日期:1998-01-01 00:00:00
abstract::Coronary artery disease causes an increase in glutamate uptake and alanine output by the heart. We assessed the effects of acute myocardial ischemia on alanine and glutamate exchange and ammonia production in 10 anesthetized open-chest domestic swine (46.9 +/- 0.7 kg). Coronary blood flow was controlled through an ext...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF00801965
更新日期:1992-03-01 00:00:00
abstract::We compared the effects of linagliptin (Lina, a DPP4 inhibitor) and GLP-1 receptor activation by exenatide followed by exendin-4 in an infusion pump (EX) on infarct size (IS), post-infarction activation of the inflammasome and remodeling in wild-type (WT) and db/db diabetic mice. Mice underwent 30 min ischemia followe...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-019-0743-0
更新日期:2019-08-06 00:00:00
abstract::We have characterized the aerobic blood-perfused isolated heart model evaluating the hemodynamics and metabolism of both the blood donor animal and the isolated organ. Anaesthesia of the blood donor with sodium pentobarbital (30 mg/kg) increases arterial concentration of non esterified fatty acids (NEFA) from 80 +/- 6...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s003950050145
更新日期:1999-06-01 00:00:00
abstract::Ventricular and atrial cardiac muscle cells isolated from the adult rat have been cultured and characterized. Once established in culture these myocytes resemble morphologically their in vivo counterparts except that they are flattened on the surface of the culture flask. These cultured cells possess differentiated ul...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
abstract::A survey was made of vagal afferents whose endings originated in cardiopulmonary areas of the Rhesus monkey. Recordings of action potentials from single fiber preparations of the left cervical vagus were made in both open and closed chest monkeys. A total of 425 receptors were identified in sixteen animals. These cons...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF02023598
更新日期:1977-07-01 00:00:00
abstract::This study was designed to identify mechanisms responsible for coronary vasodilation in response to progressive decreases in hematocrit. Isovolemic hemodilution was produced in open-chest, anesthetized swine via concurrent removal of 500 ml of arterial blood and the addition of 500 ml of 37 °C saline or synthetic plas...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-017-0654-x
更新日期:2017-09-30 00:00:00
abstract::Hemodynamics and myocardial contractility were evaluated in five unanesthetized calves during acute hypocapnic and isocapnic hypoxia and during acute hypocapnic hypoxia with beta-adrenergic blockade. Both hypocapnic and isocapnic hypoxia, with mean PaO2 levels of 33.1 and 39.1 mm Hg respectively, produced a decline in...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01909762
更新日期:1976-09-01 00:00:00
abstract::This study was aimed to assess the relationship among the voltage-dependent processes underlying the excitation-contraction coupling, viz. force restitution (FR), transmembrane Ca fluxes and Ca release. The experiments (n = 22) were performed on voltage-clamped dog trabeculae in which force and slow inward current wer...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF00795054
更新日期:1992-09-01 00:00:00
abstract::Myocytes isolated from guinea pig ventricles were voltage-clamped using patch pipettes in the whole-cell configuration. For proper voltage control fast Na+ current was blocked by TTX or inactivated by an appropriate prepulse. Zero-load cell shortening was monitored by a photoelectric device. The mechanical response to...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01907923
更新日期:1989-03-01 00:00:00
abstract::Although it has long been recognized that thyroid hormone is an effective positive inotrope, its efficacy in supporting hemodynamics in the acute setting of ischaemia and reperfusion (R) without worsening reperfusion injury remains largely unknown. Thus, we investigated the effects of triiodothyronine (T3) on reperfus...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-008-0758-4
更新日期:2009-01-01 00:00:00
abstract::Transient receptor potential melastatin-7 (TRPM7) channels have been recently reported in human atrial fibroblasts and are believed to mediate fibrogenesis in human atrial fibrillation. The present study investigates whether TRPM7 channels are expressed in human atrial myocytes using whole-cell patch voltage-clamp, RT...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-012-0282-4
更新日期:2012-09-01 00:00:00
abstract::Increase of Ca2+ concentration to 7.5 mM in the presence of 10 mM or 20 mM caffeine shifted length-tension relationships of 5 rat trabecular muscles and 5 cat papillary muscles to higher tensions. At 1max diastolic tension was enhanced from (formula: see text), for all measured points of stress-strain relationships af...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01906525
更新日期:1978-09-01 00:00:00
abstract::Short repeated cycles of peripheral ischemia/reperfusion (I/R) can protect distant organs from subsequent prolonged I/R injury; a phenomenon known as remote ischemic preconditioning (RIPC). A RIPC-mediated release of humoral factors might play a key role in this protection and vascular endothelial cells are potential ...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-015-0474-9
更新日期:2015-03-01 00:00:00
abstract::The concept of metabolic coronary flow control provides a rationale for the close relationship of coronary flow and myocardial metabolic rate of oxygen. The concept is based on the presence of an oxygen (metabolic) sensor coupled functionally to effector mechanisms, which control vascular tone. Four modes of metabolic...
journal_title:Basic research in cardiology
pub_type: 杂志文章,评审
doi:10.1007/s00395-006-0621-4
更新日期:2006-11-01 00:00:00
abstract::We chronically implanted hygroscopic occluders around the left circumflex coronary artery in 49 anesthetized young male domestic pigs and we studied the development of a collateral circulation at 4, 8, 12, and 26 weeks after implantation. At these time intervals groups of animals were again anesthetized, the hearts we...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01908204
更新日期:1989-09-01 00:00:00
abstract::Local photodynamic therapy was used to prevent neointimal hyperplasia after stenting. Slotted tube stents were placed with 16 atmospheres in porcine femoral arteries with the external diameter to match the diameter at 10 atmospheres. Animals were randomly allocated to Group 1 (stenting only); or Group 2 with stenting,...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s003950200003
更新日期:2002-03-01 00:00:00
abstract::Carotid baroreceptor stimulation (CBS) has been shown to improve cardiac dysfunction and pathological structure remodelling. This study aimed to investigate the effects of CBS on the ventricular electrophysiological properties in canines with chronic heart failure (CHF). Thirty-eight beagles were randomized into contr...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-019-0750-1
更新日期:2019-09-09 00:00:00
abstract::Hypertension and resulting left ventricular hypertrophy was induced in young male Wistar rats (60 to 70 days old) by narrowing of one renal artery (Goldblatt II). 8 and 24 weeks after operation, myocardial oxygen consumption was measured on a modified in situ heart-lung preparation with nearly isovolumetric left ventr...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01908041
更新日期:1982-05-01 00:00:00
abstract::Recent findings on the induction of anti-apoptotic gene expression in ischemic/reperfused hearts encouraged us to investigate whether ischemic/reperfused hearts may be protected against apoptosis induction. To analyze this hypothesis we performed studies on isolated perfused hearts of rat. For apoptosis induction, hea...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s003950200053
更新日期:2002-11-01 00:00:00
abstract::Toxic peroxides result when oxygen radicals react with various peroxidic precursors in tissue or blood. A colorimetric method based on reactions of malondialdehyde (MDA), a key intermediate in the formation of peroxides, has been described in fresh tissues. The present report adapts this assay to measure MDA levels in...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01910480
更新日期:1984-09-01 00:00:00
abstract::PDE3 cyclic nucleotide phosphodiesterase inhibitors raise cAMP and cGMP content in cardiac and vascular myocytes. Their administration to patients with dilated cardiomyopathy leads to improvements in hemodynamic parameters in the short term but reduces survival with chronic administration. The reasons for this 'biphas...
journal_title:Basic research in cardiology
pub_type: 杂志文章,评审
doi:10.1007/s003950200035
更新日期:2002-01-01 00:00:00
abstract::The capillary wall, due to its diffusional resistance, causes concentration differences between the vascular space and the interstitial space for substances which are released or taken up by the heart. Estimation of capillary transfer and interstitial concentration in isolated hearts, however, indicates a variable dif...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
abstract::We measured the amount of 1,2-diacylglycerol (DAG) and its fatty acid composition in hamster hearts of various ages because 1,2-DAG has been recognized to be one of the intracellular second messengers. The highest level in 1,2-DAG was detected in 30-day-old hamster hearts. The heart weight increased about 2.5 times be...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01906969
更新日期:1990-03-01 00:00:00