Abstract:
:The purpose of this study was to determine if decreased heart function after hypoxia followed by reoxygenation (H-R) is associated with increased degradation of cardiac myosin light chain 1 (MLC1) by matrix metalloproteinase-2 (MMP-2), and to investigate the effects of the increased level of peroxynitrite in the hearts of H-R animals on MLC1 degradation by MMP-2. Total of 12 newborn piglets were acutely instrumented to monitor cardiac function as assessed by stroke volume. Anesthetized piglets were block randomized to the normoxic group (n = 6), which received ventilation with room air for 6 h, or to the H-R group (n = 6), which received ventilation with 10-15% oxygen for 2 h, followed by reoxygenation with 100% oxygen for 1 h and then with 21% oxygen for 3 h. Hearts were removed and snap frozen for subsequent biochemical analyses. At the end of the 2-h hypoxia period, cardiac output, mean arterial pressure and stroke volume were significantly decreased in the H-R group. After 1 h of 100% oxygen, these parameters had increased slightly, but remained significantly lower than the normoxic controls throughout the reoxygenation period. Compared to normoxic animals, cardiac MLC1 levels were decreased and MMP-2 activity was increased in H-R animals. MMP-2 was co-localized with MLC1, and the amount of MLC1 associated with MMP-2 was higher in the hearts of H-R animals. In normoxic animals, cardiac MLC1 level was negatively, and cardiac MMP-2 activity was positively, strongly correlated with stroke volume index. This relationship was not seen in the H-R group. However, in both the normoxic group and the H-R group, the activity of cardiac MMP-2 was negatively correlated with the level of cardiac MLC1. There was a more than twofold increase in the level of nitrates, a marker for peroxynitrite formation, in the hearts of H-R animals. Mass spectrometric analyses detected peroxynitrite-induced nitration and S-nitrosylation of MLC1 protein in the hearts of H-R animals. These peroxynitrite-induced modifications of MLC1 were localized directly adjacent to the site at which MMP-2 cleaves MLC1. Peroxynitrite, formed during cardiac reoxygenation following a period of hypoxia, modifies the structure of cardiac MLC1 by nitrating and nitrosylating amino acids adjacent to the site where MMP-2 cleaves MLC1. This facilitates the degradation of MLC1 by MMP-2 and may contribute to cardiac dysfunction induced by H-R and other forms of oxidative stress. The high correlation between MMP-2 activity and MLC1 level in control animals suggests that MMP-2 may play an important role in regulating MLC1 turnover under normal physiological conditions. Determining the optimal parameters for controlled reoxygenation after hypoxia, together with pharmacological treatment with MMP-2 inhibitors and/or inhibitors of nitration/nitrosylation of MLC1, could reduce heart injury during the resuscitation of asphyxiated newborns and improve their long-term prognosis by reducing MLC1 degradation. Since the degradation of MLC1 by MMP-2 appears to be a common feature of oxidative stress, these pharmacological interventions may be useful in reducing tissue damage in other oxidative stress-related disorders as well.
journal_name
Basic Res Cardioljournal_title
Basic research in cardiologyauthors
Doroszko A,Polewicz D,Sawicka J,Richardson JS,Cheung PY,Sawicki Gdoi
10.1007/s00395-009-0035-1subject
Has Abstractpub_date
2009-11-01 00:00:00pages
669-79issue
6eissn
0300-8428issn
1435-1803journal_volume
104pub_type
杂志文章abstract::In order to clarify the genesis of the characteristic pressure and flow pulse contours of the common carotid artery of man, at first transcutaneous pulse recordings were carried out on healthy resting subjects during breathing of room air and of a mixture of 95% O2 and 5% CO2 (Carbogen). The latter was used to cause v...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01907041
更新日期:1977-11-01 00:00:00
abstract:OBJECTIVE:Ischemic or hypoxic preconditioning has been shown, in multicellular preparations, to reduce post-ischemic injury. In the present study, we attempted to develop a model of preconditioning in isolated rat myocytes in order to facilitate investigation into the mechanism of preconditioning. METHODS:The protecti...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF00788907
更新日期:1996-05-01 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::Pressure-overloaded cardiac hypertrophy was induced by abdominal aortic constriction in 10-week-old male Wistar rats. 24-26 weeks after aortic constriction, the hearts were excised and a myocardial mechanical study was performed using isolated left ventricular papillary muscles. There was no significant difference in ...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01907024
更新日期:1987-07-01 00:00:00
abstract::DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a novel inducer to promote mitochondrial apoptosis and suppress tumor growth in a variety of cells although its role in cardiovascular diseases remains obscure. This study was designed to examine the role of DNA-PKcs in cardiac ischemia reperfusion (IR) inju...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-019-0773-7
更新日期:2020-01-09 00:00:00
abstract::The ability of the rhesus monkey to form coronary collaterals was tested in ten animals. Ameroid constrictors were implanted on the left circumflex coronary artery and allowed to remain for 12 weeks. One animal died of an acute myocardial infarction nine days after surgery; the remaining animals survived without clini...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01906462
更新日期:1983-09-01 00:00:00
abstract::The terminal complement complex C5b-9 is known to participate in inflammatory processes including atherosclerosis. Inflammation appears to be a direct consequence of C5b-9-mediated cell stimulation. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors may exert anti-inflammatory effects on vascular cel...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-003-0437-4
更新日期:2003-11-01 00:00:00
abstract::Intermittent, normobaric hypoxia confers robust cardioprotection against ischemia-induced myocardial infarction and lethal ventricular arrhythmias. δ-Opioid receptor (DOR) signaling and reactive oxygen species (ROS) have been implicated in cardioprotective phenomena, but their roles in intermittent hypoxia are unknown...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-016-0538-5
更新日期:2016-03-01 00:00:00
abstract::Atherosclerotic plaques impair vascular function and can lead to arterial obstruction and tissue ischaemia. Rupture of an atherosclerotic plaque within a coronary artery can result in an acute myocardial infarction, which is responsible for significant morbidity and mortality worldwide. Prompt reperfusion can salvage ...
journal_title:Basic research in cardiology
pub_type: 杂志文章,评审
doi:10.1007/s00395-020-00829-5
更新日期:2020-11-30 00:00:00
abstract::Total cholesterol, phospholipids, and triglycerides in serum were studied during myocardial infarction in a patient group treated with glucose, insulin and potassium (GIK), and a conventionally treated group. There was no difference in the typical changes of cholesterol and phospholipids between the groups, but the GI...
journal_title:Basic research in cardiology
pub_type: 临床试验,杂志文章
doi:10.1007/BF01907206
更新日期:1983-11-01 00:00:00
abstract::Mobilization of triacylglycerol stored in heart cells is accomplished by the combined action of lysosomal (acid) lipase and microsomal monoacylglycerol lipase or carboxylesterase. Non(heparin)-releasable neutral or alkaline lipase is similar to non(readily)-releasable lipoprotein lipase (LPL). The enzyme is mainly loc...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01908026
更新日期:1984-05-01 00:00:00
abstract::Calcium transport functions of mitochondria and sarcoplasmic reticulum (SR) were studied without prior extraction using isolated rat heart myocytes permeabilized with saponin. Calcium uptake by SR was rapid and its affinity was high in comparison to calcium uptake by mitochondria, which had a higher capacity. The sens...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01907975
更新日期:1989-05-01 00:00:00
abstract::The assessment of endothelium-mediated modulation of coronary vasomotor tone in the intact human circulation under physiologic conditions requires very precise determination of both epicardial artery diameters, reflecting effects within the conduit vessels, as well as coronary blood flow, reflecting effects within the...
journal_title:Basic research in cardiology
pub_type: 杂志文章,评审
doi:10.1007/978-3-642-72461-9_18
更新日期:1991-01-01 00:00:00
abstract::Parathyroid hormone-related peptide (PTHrP) was found to improve contractile function of stunned myocardium in pigs. The peptide is released from coronary endothelial cells during ischemia and significantly improves post-ischemic recovery. The present study was aimed to decide whether such an induction of contractile ...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-005-0532-9
更新日期:2005-07-01 00:00:00
abstract::This study was designed to evaluate whether the decreased early survival rate of diabetic rats submitted to acute experimental myocardial infarction can be improved by pretreatment with lidocaine. Male Wistar rats (+/- 210 g) were rendered diabetic with i.v. injection of streptozotocin (50 mg/kg), and only those prese...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01907132
更新日期:1990-07-01 00:00:00
abstract::1. Studies on three models of cardiac hypertrophy (aortic constriction, application of isoproterenol, daily administrations of 3,3'5-triiodo-L-thyronine, respectively) reveal that the enhancement of de novo synthesis of adenine nucleotides occurs very early during the development of cardiac hypertorphy and always prec...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01906368
更新日期:1977-03-01 00:00:00
abstract::The pathogenesis and progression of hypertensive heart disease are unclear; however, both involve a genetic predisposition and environmental influences. To test the role of exogenous factors, we examined the hearts of spontaneously hypertensive rats (SHR) exposed to noise stress and ethanol intake. Twenty-two SHR and ...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF00794951
更新日期:1994-11-01 00:00:00
abstract:OBJECTIVE:Cardiac stunning is the consequence of a brief cardiac ischemia. The underlying mechanism is not completely understood. METHODS:Here we induced cardiac transient ischemia in conscious instrumented dogs by means of an occluder in the left anterior descending coronary artery (LAD). Contractile performance, mon...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-005-0577-9
更新日期:2006-05-01 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:AIMS:There is a need for better identification of patients at high risk for malignant arrhythmias who would benefit from implantable cardioverter defibrillators (ICD). The purpose of this study was to assess whether the C825T polymorphism in the G-protein beta3 subunit gene, GNB3, might serve as a genetic marker for re...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-006-0600-9
更新日期:2006-09-01 00:00:00
abstract::Receptor for advanced glycation end products (RAGE) and connective tissue growth factor (CTGF) play a key role in diabetic myocardial fibrosis, and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activation has been reported to reduce RAGE and CTGF expression. This study investigated the effects of the P...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-009-0071-x
更新日期:2010-05-01 00:00:00
abstract::It was previously reported that inhibition of carnitine synthesis by 3-(2,2,2-trimethyl-hydrazinium) propionate (MET-88) restores left ventricular (LV) systolic and diastolic function in rats with myocardial infarction (MI). Preservation of the calcium uptake function of sarcoplasmic reticulum Ca2+-ATPase (SERCA2) is ...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s003950070032
更新日期:2000-10-01 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::We hypothesized that nandrolone (ND)-abuse induces cardiac hypertrophy, increases myocardial susceptibility to ischemia/reperfusion (I/R) injury, and reduces responsiveness to postconditioning (PostC) cardioprotection. Wistar-rats were ND treated for 2 weeks (short_ND) or 10 weeks (long_ND). Vehicle-treated rats serve...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-010-0143-y
更新日期:2011-05-01 00:00:00
abstract::The aim of this study was to investigate the mechanism of beta-adrenergic preconditioning (BPC). The roles of adenosine and its receptor subtypes, the generation of oxygen free radicals (ROS) and activation of the K(ATP) channels as well as the phosphoinositide-3-kinase (PI(3)K)/PKB/Akt and extracellular signal-regula...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-012-0281-5
更新日期:2012-09-01 00:00:00
abstract::The role of the cardiac current Ik1 in arrhythmogenesis remains highly controversal. To gain further insights into the mechanisms of IK1 involvement in cardiac excitability, we studied the susceptibility of transgenic mice with altered IK1 to arrhythmia during various pharmacological and physiological challenges. Arrh...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-007-0659-y
更新日期:2007-09-01 00:00:00
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 st...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-014-0421-1
更新日期:2014-07-01 00:00:00
abstract::The available data clearly suggest large alterations in myocardial eicosanoid generation during myocardial ischaemia and demonstrate important actions of eicosanoids on myocardial function during ischaemic conditions. These actions include direct effects on the injured myocardium as well as influences on other target ...
journal_title:Basic research in cardiology
pub_type: 杂志文章,评审
doi:10.1007/978-3-662-08390-1_27
更新日期:1987-01-01 00:00:00
abstract::Because of the close anatomical association between the ventricles, the volume of one ventricle can directly affect the volume and pressure within the other ventricle. To study the mechanical coupling between the ventricles, we modeled the right and left ventricles as a two-compartment model with right wall (Crw), sep...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01907759
更新日期:1986-09-01 00:00:00
abstract::Pentostatin (2-deoxycoformycin) is a potent inhibitor of adenosine deaminase and has been demonstrated to augment endogenous adenosine levels during regional and global myocardial ischemia. Based on the rationale that increasing endogenous adenosine during ischemia may be cardioprotective, the objective of this study ...
journal_title:Basic research in cardiology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00789447
更新日期:1995-03-01 00:00:00