Involvement of mitogen-activated protein kinases in adriamycin-induced cardiomyopathy

2005 ◽  
Vol 288 (4) ◽  
pp. H1925-H1930 ◽  
Author(s):  
H. Lou ◽  
I. Danelisen ◽  
P. K. Singal
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Protein Kinases ◽  
Caspase 3 ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Male Rats ◽  
Steady Increase ◽  
Mitogen Activated Protein Kinases ◽  
Mitogen Activated Protein

The current study investigated the phosphorylation of mitogen-activated protein kinases (MAPKs) as well as pro- and anti-apoptotic proteins in adriamycin (ADR)-induced cardiomyopathy (AIC) and heart failure in rats. Modulatory effects of antioxidant probucol on the activation of MAPKs were also examined. Male rats were administered with ADR (15 mg/kg body wt ip, over 2 wk) with and without probucol (120 mg/kg body wt for 4 wk ip). Hearts from these animals were studied at 1- to 24-h as well as at 3-wk posttreatment durations. In the 3-wk group, ADR depressed cardiac function, increased left ventricular end-diastolic pressure (LVEDP), and caused dyspnea and mortality. These changes were prevented by probucol. Phosphorylation of extracellular signal-regulated kinase (ERK)1/2, in the early stage of AIC, showed a biphasic response, with a maximum increase to 513% seen at 4 h, followed by a decrease to 66.8% at 3 wk after the last injection of ADR. Phosphorylation of p38 and c-Jun NH2-terminal kinases (JNKs) showed a steady increase through 2, 4, and 24 h and 3 wk (116% to 148%). In gene microarray analysis at 3 wk (heart failure stage), mRNA expression for both ERK1/2 and p38 kinases was decreased, whereas JNK mRNA was undetectable. Probucol completely prevented these MAPK changes. Activation of caspase-3 as well as the increase in the ratio of Bax to Bcl-xl were seen at early time points (1–24 h) as well as in the heart failure stage (3 wk). It is suggested that a transient increase in ERK1/2 at a shorter interval indicate an early adaptive response, and failure of this response corresponded with heart failure. In contrast, a gradual and persistent increase in p38 and JNK MAPKs as well as in caspase-3 and the Bax-to-Bcl-xl ratio may contribute in the initiation of apoptosis and progression of heart failure. Because probucol modulated changes in cellular signaling pathways and cardiac function, it is likely that oxidative stress plays a key role in AIC and heart failure.

scholarly journals Mitogen-Activated Protein Kinases Mediate Upregulation of Hypothalamic Angiotensin II Type 1 Receptors in Heart Failure Rats

Hypertension ◽  
2008 ◽  
Vol 52 (4) ◽  
pp. 679-686 ◽  
Author(s):  
Shun-Guang Wei ◽  
Yang Yu ◽  
Zhi-Hua Zhang ◽  
Robert M. Weiss ◽  
Robert B. Felder
Keyword(s):  
Heart Failure ◽  
Angiotensin Ii ◽  
Protein Kinases ◽  
Mitogen Activated Protein Kinases ◽  
Mitogen Activated Protein

scholarly journals Nano-Curcumin Protects Against Sodium Nitrite–Induced Lung Hypoxia Through Modulation of Mitogen-Activated Protein Kinases/c-Jun NH2-Terminal Kinase Signaling Pathway

Dose-Response ◽  
2021 ◽  
Vol 19 (3) ◽  
pp. 155932582110331
Author(s):  
Ahlam Alhusaini ◽  
Sara Alhumaidan ◽  
Renad Almogren ◽  
Shaikha Alsaif ◽  
Ebtesam Alsultan ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Protein Kinases ◽  
Sodium Nitrite ◽  
Caspase 3 ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Control Group ◽  
Mitogen Activated Protein Kinases ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
Hypoxic Group

Background and objective This study was designed to compare the efficacy of curcumin (CRN) with that of nano-curcumin (N-CRN) in the mitigation of various biochemical indices in hypoxic lung induced by sodium nitrite (SN) in rats. Methods Twenty-four adult male albino rats were divided into 4 groups. Group 1: control group received carboxy methyl cellulose; Group 2: hypoxic group injected with single dose of SN (60 mg/kg, s.c.); Group 3: SN-intoxicated rats pre-injected with CRN (100 mg/kg, i.p.); and Group 4: SN-intoxicated rats pre-injected with N-CRN (100 mg/kg, i.p.). Curcumin and N-CRN were administered intraperitoneally 2 hour prior to SN intoxication. Hemoglobin concentration, serum tumor necrosis factor-alpha (TNF-α), and caspase-3 were analyzed. Gene expression of hypoxia inducible factor-1 (HIF-1α), matrix metallo-proteinases (MMP)-2, and tissue inhibitors of metalloproteinases (TIMPs)-2, as well as the protein expression of mitogen-activated protein kinases (MAPKs) and c-Jun NH2-terminal kinase (JNK) were examined in lung tissues. Results Hemoglobin level was markedly reduced, and serum TNF-α and caspase-3 were significantly elevated post SN intoxication. The lung MMP-2 and HIF-1α mRNA were overexpressed in the hypoxic group; while TIMP-2 mRNA was downregulated. Sodium nitrite administration increased proteins’ expressions of MAPK and JNK. Pretreatment with CRN or N-CRN markedly mitigated those alterations. These results were supported by histopathological examinations of lung tissue. Conclusion Interestingly, N-CRN exhibited a pronounced protective effect via suppression of inflammatory and apoptotic biomarkers and modulation of MAPK/JNK signaling pathway.

scholarly journals Central and peripheral factors mechanistically linked to exercise intolerance in heart failure with reduced ejection fraction

2019 ◽  
Vol 317 (2) ◽  
pp. H434-H444 ◽  
Author(s):  
Jesse C. Craig ◽  
Trenton D. Colburn ◽  
Jacob T. Caldwell ◽  
Daniel M. Hirai ◽  
Ayaka Tabuchi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Exercise Tolerance ◽  
Critical Speed ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Exercise Intolerance ◽  
Time To Exhaustion ◽  
Central Function ◽  
White Gastrocnemius

Exercise intolerance is a primary symptom of heart failure (HF); however, the specific contribution of central and peripheral factors to this intolerance is not well described. The hyperbolic relationship between exercise intensity and time to exhaustion (speed-duration relationship) defines exercise tolerance but is underused in HF. We tested the hypotheses that critical speed (CS) would be reduced in HF, resting central functional measurements would correlate with CS, and the greatest HF-induced peripheral dysfunction would occur in more oxidative muscle. Multiple treadmill-constant speed runs to exhaustion were used to quantify CS and D′ (distance coverable above CS) in healthy control (Con) and HF rats. Central function was determined via left ventricular (LV) Doppler echocardiography [fractional shortening (FS)] and a micromanometer-tipped catheter [LV end-diastolic pressure (LVEDP)]. Peripheral O2 delivery-to-utilization matching was determined via phosphorescence quenching (interstitial Po2, Po2 is) in the soleus and white gastrocnemius during electrically induced twitch contractions (1 Hz, 8V). CS was lower in HF compared with Con (37 ± 1 vs. 44 ± 1 m/min, P < 0.001), but D′ was not different (77 ± 8 vs. 69 ± 13 m, P = 0.6). HF reduced FS (23 ± 2 vs. 47 ± 2%, P < 0.001) and increased LVEDP (15 ± 1 vs. 7 ± 1 mmHg, P < 0.001). CS was related to FS ( r = 0.72, P = 0.045) and LVEDP ( r = −0.75, P = 0.02) only in HF. HF reduced soleus Po2 is at rest and during contractions (both P < 0.01) but had no effect on white gastrocnemius Po2 is ( P > 0.05). We show in HF rats that decrements in central cardiac function relate directly with impaired exercise tolerance (i.e., CS) and that this compromised exercise tolerance is likely due to reduced perfusive and diffusive O2 delivery to oxidative muscles. NEW & NOTEWORTHY We show that critical speed (CS), which defines the upper boundary of sustainable activity, can be resolved in heart failure (HF) animals and is diminished compared with controls. Central cardiac function is strongly related with CS in the HF animals, but not controls. Skeletal muscle O2 delivery-to-utilization dysfunction is evident in the more oxidative, but not glycolytic, muscles of HF rats and is explained, in part, by reduced nitric oxide bioavailability.

scholarly journals Renal denervation improves cardiac function in rats with chronic heart failure: Effects on expression of β-adrenoceptors

2016 ◽  
Vol 311 (2) ◽  
pp. H337-H346 ◽  
Author(s):  
Hong Zheng ◽  
Xuefei Liu ◽  
Neeru M. Sharma ◽  
Kaushik P. Patel
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Left Ventricle ◽  
Cardiac Function ◽  
Renal Denervation ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Sprague Dawley ◽  
Cardiac Damage ◽  
Sprague Dawley Rats

Chronic activation of the sympathetic drive contributes to cardiac remodeling and dysfunction during chronic heart failure (HF). The present study was undertaken to assess whether renal denervation (RDN) would abrogate the sympathoexcitation in HF and ameliorate the adrenergic dysfunction and cardiac damage. Ligation of the left coronary artery was used to induce HF in Sprague-Dawley rats. Four weeks after surgery, RDN was performed, 1 wk before the final measurements. At the end of the protocol, cardiac function was assessed by measuring ventricular hemodynamics. Rats with HF had an average infarct area >30% of the left ventricle and left ventricular end-diastolic pressure (LVEDP) >20 mmHg. β1- and β2-adrenoceptor proteins in the left ventricle were reduced by 37 and 49%, respectively, in the rats with HF. RDN lowered elevated levels of urinary excretion of norepinephrine and brain natriuretic peptide levels in the hearts of rats with HF. RDN also decreased LVEDP to 10 mmHg and improved basal dP/d t to within the normal range in rats with HF. RDN blunted loss of β1-adrenoceptor (by 47%) and β2-adrenoceptor (by 100%) protein expression and improved isoproterenol (0.5 μg/kg)-induced increase in +dP/d t (by 71%) and −dP/d t (by 62%) in rats with HF. RDN also attenuated the increase in collagen 1 expression in the left ventricles of rats with HF. These findings demonstrate that RDN initiated in chronic HF condition improves cardiac function mediated by adrenergic agonist and blunts β-adrenoceptor expression loss, providing mechanistic insights for RDN-induced improvements in cardiac function in the HF condition.

scholarly journals Phenotype and Mitogen Activated Protein Kinases in Pressure and Volume Induced Left Ventricular Hypertrophies

1999 ◽  
Vol 45 (4, Part 2 of 2) ◽  
pp. 18A-18A
Author(s):  
Assad I Alhroob ◽  
Somkiat Sopontammarak ◽  
Paul A Ingram ◽  
Sunthorn Muangmingsuk ◽  
Rene A Arcilla ◽  
...  
Keyword(s):  
Protein Kinases ◽  
Left Ventricular ◽  
Mitogen Activated Protein Kinases ◽  
Mitogen Activated Protein

scholarly journals A new model of congestive heart failure in rats

2011 ◽  
Vol 301 (3) ◽  
pp. H994-H1003 ◽  
Author(s):  
Jiqiu Chen ◽  
Elie R. Chemaly ◽  
Li Fan Liang ◽  
Thomas J. LaRocca ◽  
Elisa Yaniz-Galende ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Cardiac Function ◽  
Systolic Function ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Remote Myocardium ◽  
Male Rats ◽  
Lv Function ◽  
New Model

Current rodent models of ischemia/infarct or pressure-volume overload are not fully representative of human heart failure. We developed a new model of congestive heart failure (CHF) with both ischemic and stress injuries combined with fibrosis in the remote myocardium. Sprague-Dawley male rats were used. Ascending aortic banding (Ab) was performed to induce hypertrophy. Two months post-Ab, ischemia-reperfusion (I/R) injury was induced by ligating the left anterior descending (LAD) artery for 30 min. Permanent LAD ligation served as positive controls. A debanding (DeAb) procedure was performed after Ab or Ab + I/R to restore left ventricular (LV) loading properties. Cardiac function was assessed by echocardiography and in vivo hemodynamic analysis. Myocardial infarction (MI) size and myocardial fibrosis were assessed. LV hypertrophy was observed 4 mo post-Ab; however, systolic function was preserved. LV hypertrophy regressed within 1 mo after DeAb. I/R for 2 mo induced a small to moderate MI with mild impairment of LV function. Permanent LAD ligation for 2 mo induced large MI and significant cardiac dysfunction. Ab for 2 mo followed by I/R for 2 mo (Ab + I/R) resulted in moderate MI with significantly reduced ejection fraction (EF). DeAb post Ab + I/R to reduce afterload could not restore cardiac function. Perivascular fibrosis in remote myocardium after Ab + I/R + DeAb was associated with decreased cardiac function. We conclude that Ab plus I/R injury with aortic DeAb represents a novel model of CHF with increased fibrosis in remote myocardium. This model will allow the investigation of vascular and fibrotic mechanisms in CHF characterized by low EF, dilated LV, moderate infarction, near-normal aortic diameter, and reperfused coronary arteries.

Sign in / Sign up

Export Citation Format

Share Document