scholarly journals Resveratrol Attenuated Low Ambient Temperature-Induced Myocardial Hypertrophy via Inhibiting Cardiomyocyte Apoptosis

2015 ◽  
Vol 35 (6) ◽  
pp. 2451-2462 ◽  
Author(s):  
Kun Yin ◽  
Liang Zhao ◽  
Dan Feng ◽  
Wenya Ma ◽  
Yu Liu ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Ambient Temperature ◽  
Mapk Pathway ◽  
Weight Ratio ◽  
Treated Mouse ◽  
Cardiomyocyte Apoptosis ◽  
Heart Weight ◽  
Control Group ◽  
Resveratrol Treatment ◽  
Low Ambient Temperature

Background/Aims: Low ambient temperature is an important risk factor for cardiovascular diseases, and has been shown to lead to cardiac hypertrophy. In this study, we aim to investigate if Resveratrol may inhibit cold exposure-induced cardiac hypertrophy in mice, and if so to clarify its molecular mechanism. Methods: Adult male mice were randomly assigned to Control group (kept at room temperature), Cold group (kept at low air temperature range from 3°C to 5°C) and Resveratrol treatment group (100mg/kg/day) for eight weeks. HE staining, Masson staining and Transmission electron microscopy were employed to detect cardiac structure, fibrosis and myocardial ultrastructure, respectively. Echocardiogram was used to measure myocardial functions. Western blot was used to detect the expression of MAPK pathway and apoptotic proteins. TUENL assay was performed to evaluate cardiomyocyte apoptosis. qRT-PCR was employed to measure the mRNA level. Results: Cold-treated mice showed a higher heart/body weight ratio and heart weight/tibia length ratio compared with control mice, and Resveratrol treatment may suppress these changes in cold-treated mice. Myocardial cross-section area and cardiac collagen volume were larger in cold group than control group, which also can be attenuated by Resveratrol treatment. Also, Resveratrol improved the ultrastructure damage of myocardium such as myofibril disarray in cold group. Echocardiogram measurement showed that EF and FS values in cold group declined apparently as compared to control group, and Resveratrol may improve the reduction of heart functions. The expression of p-JNK, p-p38 and p-ERK relative to total JNK, p38 and ERK in cold group was not altered in cold group and Resveratrol group as compared to control group. Cold-treated mouse hearts also showed the upregulation of hypertrophy-related miRNA-miR-328 but not miR-23a, and Resveratrol treatment can inhibit the increase of miR-328. Finally, Resveratrol treatment also may suppress apoptosis of myocardium in cold-treated mouse hearts via inhibiting Bax and caspase-3 activation. Conclusion: In summary, low ambient temperature can cause enlarged heart, ultrastructure damage of myocardium and weakened functions, and Resveratrol treatment effectively suppressed these changes at least partially via inhibiting cardiomyocyte apoptosis.

scholarly journals PO-148 Effect of Aerobic Exercise on the Expression of CaMKIIδ/MEF2 in Hypertensive and Physiological Cardiac Hypertrophy

2018 ◽  
Vol 1 (4) ◽  
Author(s):  
Man Zhu ◽  
Lijun Shi
Keyword(s):  
Body Weight ◽  
Cardiac Hypertrophy ◽  
Aerobic Exercise ◽  
Weight Ratio ◽  
Exercise Group ◽  
The Body ◽  
Expression Level ◽  
Heart Weight ◽  
Control Group ◽  
Body Weight Ratio

Objective The type II calcium/calmodulin-dependent protein kinase IIδ (CaMKIIδ) signal plays a key role in the development of cardiac hypertrophy. This study used CaMKIIδ as an entry point to investigate the mechanism of moderate-intensity aerobic exercise affecting myocardial function. Methods Male spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats (WKYs), 12 weeks age, were randomly divided into aerobic exercise group (SHR-EX/WKY-EX) and sedentary control group (SHR-SED/WKY-SED), with 12 rats in each group. The aerobic exercise group conducted an 8-week treadmill exercise training with a slope of 0°, 20m/min (about 55-65% of maximal aerobic velocity), 60min/day, and 5d/wk. The control group did not exercise. The body weight of each group of rats was measured weekly and the blood pressure of the rats was measured non-invasively. After 8 weeks, the hearts of SHR-EX group, WKY-EX group, SHR-SED group and WKY-SED group were weighed, and then myocardial tissue sections were taken for HE staining to observe the thickness of the ventricular wall and the morphology of myocardial cells. The expression of CaMKIIδ and MEF2 in each group was determined by Western blotting. Results (1) The body weight of SHR-SED group was significantly higher than that of SHR-EX group (p<0.01), and the heart weight of rats in exercise group changed significantly. The WKY-EX group had greater heart weight than the WKY-SED group, and the SHR-SED group was heavier than the SHR-EX group (p<0.05). The heart weight/body weight ratio of the WKY-EX group was significantly higher than that of the WKY-SED group (p<0.01). The heart weight/body weight ratio of SHR-EX group and SHR-SED group was higher than that of WKY-EX group and WKY-SED group (p<0.01). (2) Compared with the WKY-SED group, the SHR-SED group had loose interstitial cells and increased single cell area. The SHR-EX group is more compact than the SHR-SED group, and the cell cross-sectional area is reduced. (3) The expression of CaMKIIδ protein in SHR-EX group was significantly lower than that in SHR-SED group (p<0.01), but the expression level of CaMKIIδ in WKY-EX group was significantly higher than that in WKY-SED group (p<0.01). The expression level of CaMKIIδ was significantly higher in the SHR-SED group than in the WKY-SED group. In addition, the expression of MEF2 protein in SHR-EX group and WKY-SED group was significantly lower than that in SHR-SED group (p<0.01), while the MEF2 expression level in WKY-EX group was higher than WKY-SED group and SHR-EX group (p<0.05). Conclusions There is an interaction between aerobic exercise and hypertension. Aerobic exercise can effectively delay the development of hypertensive cardiac hypertrophy by regulating the expression of CaMKIIδ and MEF2 protein in the myocardium, but it can also cause cardiac hypertrophy in normal heart. It is one of the important mechanisms affecting the myocardial morphology and function.    

Abstract 13798: Ablation of the Hypertension Candidate Gene ATP2B1 Results in Increased Blood Pressure and Cardiac Hypertrophic Remodeling

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Sally K Hammad ◽  
Min Zi ◽  
Sukhpal Prehar ◽  
Robert Little ◽  
Ludwig Neyses ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiac Hypertrophy ◽  
Diastolic Pressure ◽  
Association Studies ◽  
Weight Ratio ◽  
Blood Pressure Regulation ◽  
Heart Weight ◽  
Genome Wide Association Studies ◽  
Pressure Regulation ◽  
The Impact

Introduction: Hypertension is a major risk factor for cardiac hypertrophy and heart failure. Genome wide association studies have recently identified single nucleotide polymorphisms in ATP2B1 , the gene encoding the calcium extrusion pump, plasma membrane calcium ATPase (PMCA1), as having a strong association with hypertension risk. Hypothesis: PMCA1 plays an important role in regulation of blood pressure and protection against hypertension and cardiac hypertrophy. Aims: We aim to examine whether there is a functional link between PMCA1 and blood pressure regulation, and the development of hypertension. And to determine the impact this link may have on cardiac structure and function. Methods and Results: To study the role of PMCA1 we generated a global PMCA1 heterozygous knockout mouse (PMCA1 Ht ). PMCA1 Ht mice had 46% to 52% reduction in PMCA1 protein expression compared to the WT, in aorta, heart, kidney and brain. To study the mice under hypertensive stress conditions, 3 month old PMCA1 Ht and wild type (WT) mice were infused via minipump with angiotensin II (1mg/Kg/daily) or water as a control. Upon angiotensin treatment, PMCA1 Ht mice showed a significantly greater increase in systolic (62.24±3.05 mmHg) and diastolic pressure (52.68±4.67 mmHg), in comparison to the WT (33.37±2.91 mmHg and 23.94±4.56 mmHg, respectively), P<0.001, n=12. Moreover, PMCA1 Ht mice showed a significantly greater hypertrophic response as indicated by a greater heart weight to tibia length ratio, cardiomyocyte cell size (410±18.7 μm 2 ), compared to WT mice (340.4±9.8 μm 2 ), and increased expression of B-type natriuretic peptide (BNP), 2.36 ± 0.25 fold change, n =5-6, P< 0.01. Echocardiography showed no significant changes between PMCA1 Ht and WT mice, in heart rate, and in cardiac function, as indicated by fractional shortening and ejection fraction. In addition, PMCA1 Ht mice showed no sign of lung congestion as indicated by lung weight to body weight ratio. Conclusion: ATP2B1 deletion leads to increased blood pressure and cardiac hypertrophy. This provides functional evidence that PMCA1 is involved in blood pressure regulation and protects against the development of hypertension and cardiac hypertrophy.

scholarly journals Regression of gestational diabetes induced cardiomegaly in offspring of diabetic rat

2009 ◽  
Vol 24 (4) ◽  
pp. 251-255 ◽  
Author(s):  
Honório Sampaio Menezes ◽  
Cláudio Galeano Zettler ◽  
Alice Calone ◽  
Jackson Borges Corrêa ◽  
Carla Bartuscheck ◽  
...  
Keyword(s):  
Body Weight ◽  
Wistar Rats ◽  
Weight Ratio ◽  
Diabetic Rats ◽  
Heart Weight ◽  
Diabetic Rat ◽  
Control Group ◽  
Computer Assisted ◽  
Significant Difference ◽  
Levene Test

PURPOSE: To compare body weight and length, heart weight and length, heart-to-body weight ratio, glycemia, and morphometric cellular data of offspring of diabetic rats (ODR) and of normal rats (control). METHODS: Diabetes was induced in 3 pregnant Wistar rats, bearing 30 rats, on the 11th day after conception by intraperitoneal injection of 50 mg/kg of streptozotocin. Six normal pregnant Wistar rats, bearing 50 rats, made up the control group. Morphometric data were obtained using a scale for the weight, length, heart and body measurements. Morphometric cellular data were obtained by a computer assisted method applied to the measurements of myocytes. Statistical analysis utilized Student's t-test, ANOVA and Levene test. RESULTS: Control offspring had greater mean body weight and length than offspring of diabetic rats (p < 0.001). Heart weight and length and heart-to-body ratios of newborn rats differed between groups at birth (p < 0.001), but showed no difference at 21 days. Mean nuclei area and perimetric value of the myocytes decrees throughout the first 21 days of life (p < 0.01) in the diabetic group. CONCLUSIONS: Heart hypertrophy on the offspring of diabetic rats at birth was demonstrated by the significant difference between the groups. After the eleventh day, no difference was found, which confirmed regression of cardiomegaly. The significant difference between the first and the 21th day of life, for nuclei area feature, demonstrate regression of cardiac hypertrophy in the offspring of diabetic rats.

Abstract 182: CTRP9 - A Novel Cardiac Derived Secreted Factor With Anti-hypertrophic Properties

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Astrid H Breitbart ◽  
Florian Brandes ◽  
Oliver Müller ◽  
Natali Froese ◽  
Mortimer Korf-Klingebiel ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Real Time ◽  
Real Time Pcr ◽  
Weight Ratio ◽  
Neonatal Rat ◽  
Heart Weight ◽  
Cardiomyocyte Hypertrophy ◽  
Quantitative Real Time Pcr ◽  
Rat Cardiomyocytes ◽  
Knock Out

Background: CTRP9 (also called C1qtnf9) is a newly discovered secreted protein and a paralog of adiponectin. The biological functions of CTRP9, however, are still largely unknown. Results: Although previous data from a semi-quantitative real-time PCR had suggested that CTRP9 is mainly secreted by adipose tissue, we found its mRNA to be predominantly expressed in the heart by quantitative real-time PCR. Interestingly, we identified CTRP9 mRNA as significantly upregulated in hypertrophied mouse hearts (after 2 weeks of aortic constriction, TAC) as well as in hypertrophied human hearts (24±4-fold versus healthy human myocardium; p<0.01). LacZ staining in myocardial sections of C1qtnf9 tm1(KOMP)Vlcg mice (knock-out for CTRP9, containing a lacZ cassette to replace exon 1-3 of the gene) revealed exclusive expression of CTRP9 in capillary and venous endothelial cells. Adenoviral overexpression of CTRP9 or recombinant CTRP9 strongly inhibited cardiomyocyte hypertrophy (assessed as cell size, protein/DNA-ratio, expression of skeletal α-actin) after stimulation with phenylephrine (PE). Accordingly, myocardial overexpression of CTRP9 via a cardioselective adeno-associated virus (AAV9-CTRP9) in mice dramatically reduced cardiac hypertrophy after two weeks of pressure overload (heart weight/body weight ratio, HW/BW in mg/g: AAV9-control 6.5±0.2 versus AAV9-CTRP9 5.6±0.2; p<0.01). In turn, downregulation of CTRP9 by a specific siRNA aggravated cardiomyocyte growth in response to PE in vitro and CTRP9 knock-out (KO) mice exerted an enhanced hypertrophic response after two weeks of TAC in vivo (% increase in HW/BW versus sham: wild-type 77±13, KO 106±9; p<0.05). Mechanistically, we found that CTRP9 binds to the adiponectin receptor 1 (AdipoR1) and inhibits prohypertrophic mTOR signalling in cardiac myocytes. SiRNA mediated downregulation of AdipoR1 or mTOR in neonatal rat cardiomyocytes abolished the anti-hypertrophic effect of CTRP9. Conclusion: Endothelial cell derived CTRP9 inhibits cardiac hypertrophy through binding to AdipoR1 and inhibition of the mTOR pathway in cardiomyocytes. Therefore, myocardial application of CTRP9 could be a novel strategy to combat pathological cardiac hypertrophy.

Antihyperlipidemic and Antiobesity potential of Aquilaria agallocha & Borago officinalis in Fixed Dose Combination; A Contingent Probe with Atorvastatin & Orlistat

2021 ◽  
Vol 17 ◽  
Author(s):  
Rohima Oraon ◽  
Tarique Mahmood ◽  
Arshiya Shamim ◽  
Farogh Ahsan ◽  
Mohammad Shariq ◽  
...  
Keyword(s):  
Weight Ratio ◽  
Good Control ◽  
Fixed Dose Combination ◽  
Atherogenic Index ◽  
Heart Weight ◽  
Fixed Dose ◽  
Control Group ◽  
High Dose ◽  
Borago Officinalis ◽  
Dose Combination

: Hyperlipidemia and Obesity have been an alarmingly rising health disorders for the past few decades worldwide. They eventually pave way for cardiovascular and other metabolic health risks that are manifested with elevated blood lipid levels. Atherosclerosis, Coronary artery disease and Cerebrovascular diseases, are some major complications of hyperlipidemia. The current clinically available drugs like, Statins & HMG-Co-A inhibitors have a good control on hyperlipidemia but present many insalubrious effects like myopathy & hepatotoxicity that questions their risk-benefit ratio. The current study was designed to develop a fixed-dose combination (FDC) of extracts of Aquilaria agallocha and Borago officinalis, to delve into therapeutic resources that have synergistic benefits and could overpower the adverse effects of modern therapy. These plants are well reported for cardioprotective, immunomodulatory and hepatoprotective potentials. The FDC developed with these plants was examined for its antihyperlipidemic and antiobesity potential in HFD fed animal model (Vijaya et al) for Hyperlipidemia. The extracts from leaves of Borago officinalis and Aquilaria agallocha were administered perorally for 28 days in a fixed dose combination (FDC) in HFD fed rats. The physical and the biochemical parameters; viz, the gross examination of liver, heart, heart weight/body weight ratio, atherogenic index, various hepatic & cardiac biomarker enzymes and serum lipid markers were scrutinized. The result of the study suggested that both the low and high dose of the FDC of Aquilaria agallocha & Borago officinalis has significant Anti-Hyperlipidemic and Anti-Obesity potential against High-fat diet-induced Hyperlipidemia and Obesity when compared to disease control group (at p<0.01 & p<0.001) and their effects were at par with clinically established drugs Atorvastatin & Orlistat.

scholarly journals PKC-β is not necessary for cardiac hypertrophy

2001 ◽  
Vol 280 (5) ◽  
pp. H2264-H2270 ◽  
Author(s):  
Brian B. Roman ◽  
David L. Geenen ◽  
Michael Leitges ◽  
Peter M. Buttrick
Keyword(s):  
Cardiac Hypertrophy ◽  
Gene Knockout ◽  
Weight Ratio ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Heart Weight ◽  
Hypertrophic Response ◽  
Pathological Hypertrophy ◽  
Pkc Β ◽  
And Control

Studies in human and rodent models have shown that activation of protein kinase C-β (PKC-β) is associated with the development of pathological hypertrophy, suggesting that ablation of the PKC-β pathway might prevent or reverse cardiac hypertrophy. To explore this, we studied mice with targeted disruption of the PKC-β gene (knockout, KO). There were no detectable differences in expression or distribution of other PKC isoforms between the KO and control hearts as determined by Western blot analysis. Baseline hemodynamics were measured using a closed-chest preparation and there were no differences in heart rate and arterial or left ventricular pressure. Mice were subjected to two independent hypertrophic stimuli: phenylephrine (Phe) at 20 mg · kg−1 · day−1 sq infusion for 3 days, and aortic banding (AoB) for 7 days. KO animals demonstrated an increase in heart weight-to-body weight ratio (Phe, 4.3 ± 0.6 to 6.1 ± 0.4; AoB, 4.0 ± 0.1 to 5.8 ± 0.7) as well as ventricular upregulation of atrial natriuretic factor mRNA analogous to those seen in control animals. These results demonstrate that PKC-β expression is not necessary for the development of cardiac hypertrophy nor does its absence attenuate the hypertrophic response.

Transient outward current in catecholamine-induced cardiac hypertrophy in the rat

1996 ◽  
Vol 271 (6) ◽  
pp. H2360-H2367 ◽  
Author(s):  
J. Meszaros ◽  
K. O. Ryder ◽  
G. Hart
Keyword(s):  
Cardiac Hypertrophy ◽  
Weight Ratio ◽  
Outward Current ◽  
Cell Voltage ◽  
Underlying Mechanism ◽  
Left Ventricular ◽  
Daily Injection ◽  
Heart Weight ◽  
Inactivation Kinetics ◽  
Transient Outward Current

We have demonstrated that a daily injection of isoproterenol (5 mg/kg ip) for 7 days induces a 30% increment in heart weight-to-body weight ratio and prolongs the action potential duration (APD) in male Wistar rats. The underlying mechanism of the prolonged APD was investigated in this model of hypertrophy by measuring the transient outward potassium current (Ito) in left ventricular myocytes of the rat with whole cell voltage-clamp techniques. Cell membrane capacitance was increased by 39%: 122 +/- 3 (n = 23) and 171 +/- 5 (SE) pF (n = 20) in control and hypertrophy, respectively (P < 0.001). Ito was evoked in sodium-free solutions containing 0.5 mM Ca2+ and 2 mM Co2+ by step depolarizations from a holding potential of -80 mV. The amplitude of the 4-aminopyridine-sensitive Ito (at 70 mV) was reduced by 28% in hypertrophy: 3.2 +/- 0.3 (n = 23) and 2.3 +/- 0.4 (SE) nA (n = 20) in control and hypertrophy, respectively (P < 0.05). When normalized for cell capacitance, the reduction was much larger: 26.4 +/- 2.5 and 13.1 +/- 1.8 pA/pF in control and hypertrophy, respectively (P < 0.001). The voltage dependence of Ito was similar in both cell types. No change was observed in the steady-state activation and inactivation kinetics in the two groups, nor was there a change in the time dependence of inactivation. The recovery from inactivation of Ito when fitted with a monoexponential function was not changed significantly in hypertrophy: time constants = 8.2 +/- 0.4 (n = 13) and 8.3 +/- 0.3 ms (n = 12) in control and hypertrophy, respectively. These results show that Ito density is decreased in catecholamine-induced cardiac hypertrophy, but current kinetics are not affected. The reduced Ito density may underlie the prolongation of APD in this model of hypertrophy.

scholarly journals Allylmethylsulfide, a Sulfur Compound Derived from Garlic, Attenuates Isoproterenol-Induced Cardiac Hypertrophy in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Soheb Anwar Mohammed ◽  
Bugga Paramesha ◽  
Yashwant Kumar ◽  
Ubaid Tariq ◽  
Sudheer Kumar Arava ◽  
...  
Keyword(s):  
Body Weight ◽  
Cardiac Hypertrophy ◽  
Weight Ratio ◽  
Chronic Administration ◽  
The Body ◽  
Heart Weight ◽  
Serum Biochemical ◽  
Enalapril Treatment ◽  
Histopathological Investigation

Allylmethylsulfide (AMS) is a novel sulfur metabolite found in the garlic-fed serum of humans and animals. In the present study, we have observed that AMS is safe on chronic administration and has a potential antihypertrophic effect. Chronic administration of AMS for 30 days did not cause any significant differences in the body weight, electrocardiogram, food intake, serum biochemical parameters, and histopathology of vital organs. Single-dose pharmacokinetics of AMS suggests that AMS is rapidly metabolized into Allylmethylsulfoxide (AMSO) and Allylmethylsulfone (AMSO2). To evaluate the efficacy of AMS, cardiac hypertrophy was induced by subcutaneous implantation of ALZET® osmotic minipump containing isoproterenol (~5 mg/kg/day), cotreated with AMS (25 and 50 mg/kg/day) and enalapril (10 mg/kg/day) for 2 weeks. AMS and enalapril significantly reduced cardiac hypertrophy as studied by the heart weight to body weight ratio and mRNA expression of fetal genes (ANP and β-MHC). We have observed that TBARS, a parameter of lipid peroxidation, was reduced and the antioxidant enzymes (glutathione, catalase, and superoxide dismutase) were improved in the AMS and enalapril-cotreated hypertrophic hearts. The extracellular matrix (ECM) components such as matrix metalloproteinases (MMP2 and MMP9) were significantly upregulated in the diseased hearts; however, with the AMS and enalapril, it was preserved. Similarly, caspases 3, 7, and 9 were upregulated in hypertrophic hearts, and with the AMS and enalapril treatment, they were reduced. Further to corroborate this finding with in vitro data, we have checked the nuclear expression of caspase 3/7 in the H9c2 cells treated with isoproterenol and observed that AMS cotreatment reduced it significantly. Histopathological investigation of myocardium suggests AMS and enalapril treatment reduced fibrosis in hypertrophied hearts. Based on our experimental results, we conclude that AMS, an active metabolite of garlic, could reduce isoproterenol-induced cardiac hypertrophy by reducing oxidative stress, apoptosis, and stabilizing ECM components.

scholarly journals Attenuation of Low Ambient Temperature-Induced Myocardial Hypertrophy by Atorvastatin via Promoting Bcl-2 Expression

2017 ◽  
Vol 41 (1) ◽  
pp. 286-295 ◽  
Author(s):  
Jing Liang ◽  
Kun Yin ◽  
Xuefeng Cao ◽  
Zhenbo Han ◽  
Qi Huang ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Low Temperature ◽  
Ambient Temperature ◽  
Cold Exposure ◽  
Cardiac Fibrosis ◽  
Myocardial Hypertrophy ◽  
Heart Weight ◽  
Electronic Microscopy ◽  
Transmission Electronic Microscopy ◽  
Low Ambient Temperature

Background/Aims: It is well documented that myocardial hypertrophy is associated with low ambient temperature. Atorvastatin (Atv) has been shown to protect against atherosclerosis, cardiac fibrosis, ischemia/reperfusion injury, etc. In this study, we aim to determine whether atorvastatin is effective in the treatment of myocardial hypertrophy induced by cold exposure and to shed light on underlying mechanism. Methods: The mice aged 4-week were randomized to Control (Ctl) group (raised at room temperature), Cold group (raised at 3-5ºC) and Atv treatment group (raised at 3-5ºC followed by 10mg/kg/day Atv infusion). Echocardiography (ECG), HE, TUNEL and Masson’s trichrome staining, and Transmission electronic microscopy were performed to analyze cardiac function, myocardial hypertrophy, cardiac fibrosis, apoptosis and cardiomyocyte ultrastructure, respectively. Western blot was carried out to determine the involvement of MAPK and apoptosis pathways. Results: Exposure of mice to low temperature induced myocardial hypertrophic growth characterized by the elevation of heart/body weight index and heart weight /tibia length index, compared with control mice. Atv treatment attenuated cardiac hypertrophy induced by cold exposure; Atv also attenuated the increase of cross-sectional area of cardiomyocytes and cardiac collagen content fraction in mice exposed to cold. ECG showed that the decline of cardiac functions including the elevated left ventricular systolic/diastolic internal dimension (LVIDs/d) and fractional shortening (FS) in mice with cold exposure was also inhibited by Atv treatment. Transmission electronic microscopy uncovered that Atv attenuated mitochondrial injury induced by cold exposure in mice. In addition, systolic blood pressure was gradually increased in mice exposed to cold temperature, and Atv treatment significantly inhibited the elevation of blood pressure in cold-treated mice. Mechanistically, mitogen-activated protein kinase (MAPK) signal was not altered in mice exposed to cold, and Atv did not affect MAPK signal in cold-treated mice. But Atv mitigated the reduction of Bcl-2/Bax level in heart of cold-treated mice. Conclusion: Atv attenuated myocardial hypertrophy induced by cold exposure through inhibiting the downregulation of Bcl-2 in heart. It may provide a novel strategy for low temperature-induced myocardial hypertrophy treatment.

NF-κB activation is required for the development of cardiac hypertrophy in vivo

2004 ◽  
Vol 287 (4) ◽  
pp. H1712-H1720 ◽  
Author(s):  
Yuehua Li ◽  
Tuanzhu Ha ◽  
Xiang Gao ◽  
Jim Kelley ◽  
David L. Williams ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Natriuretic Peptide ◽  
Weight Ratio ◽  
Dominant Negative ◽  
Heart Weight ◽  
Dominant Negative Mutant ◽  
Body Weight Ratio ◽  
Aortic Banding ◽  
Important Target

In the present study, we examined whether NF-κB activation is required for cardiac hypertrophy in vivo. Cardiac hypertrophy in rats was induced by aortic banding for 1, 3, and 5 days and 1–6 wk, and age-matched sham-operated rats served as controls. In a separate group of rats, an IκB-α dominant negative mutant (IκB-αM), a superrepressor of NF-κB activation, or pyrrolidinedithiocarbamate (PDTC), an antioxidant that can inhibit NF-κB activation, was administered to aortic-banded rats for 3 wk. The heart weight-to-body weight ratio was significantly increased at 5 days after aortic banding, peaked at 4 wk, and remained elevated at 6 wk compared with age-matched sham controls. Atrial natriuretic peptide and brain natriuretic peptide mRNA expressions were significantly increased after 1 wk of aortic banding, reached a maximum between 2 and 3 wk, and remained increased at 6 wk compared with age-matched sham controls. NF-κB activity was significantly increased at 1 day, reached a peak at 3 wk, and remained elevated at 6 wk, and IKK-β activity was significantly increased at 1 day, peaked at 5 days, and then decreased but remained elevated at 6 wk after aortic banding compared with age-matched sham controls. Inhibiting NF-κB activation in vivo by cardiac transfection of IκB-αM or by PDTC treatment significantly attenuated the development of cardiac hypertrophy in vivo with a concomitant decrease in NF-κB activity. Our results suggest that NF-κB activation is required for the development of cardiac hypertrophy in vivo and that NF-κB could be an important target for inhibiting the development of cardiac hypertrophy in vivo.

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