Inhibition of Matrix Metalloproteinases Prevents Cardiac Hypertrophy Induced by β-Adrenergic Stimulation in Rats

2003 ◽  
Vol 42 (2) ◽  
pp. 174-181 ◽  
Author(s):  
Shoko Miura ◽  
Isao Ohno ◽  
Jun Suzuki ◽  
Ko Suzuki ◽  
Shinji Okada ◽  
...  
Keyword(s):  
Matrix Metalloproteinases ◽  
Cardiac Hypertrophy ◽  
Adrenergic Stimulation

Abstract 20385: Pregnancy-Induced Cardiac Hypertrophy is Accompanied by Unique Contractile Properties Not Seen in Other Forms of Physiological Hypertrophy

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jessica Tyrrell ◽  
Kaitlyn Kennard ◽  
Catherine Makarewich ◽  
Beth A Bailey
Keyword(s):  
Cardiac Hypertrophy ◽  
Late Pregnancy ◽  
Calcium Transient ◽  
Contractile Properties ◽  
Receptor Protein ◽  
Ca Channel ◽  
Adrenergic Stimulation ◽  
Twitch Contraction ◽  
Relaxation Phase ◽  
Near Term

Background: Cardiac hypertrophy accompanying pregnancy has generally been categorized as physiologic hypertrophy similar to that seen with exercise, however a reduction in cardiac function in late pregnancy has been suggested. Furthermore, the hemodynamic stress of pregnancy can induce a maladaptive, pathologic hypertrophy in a small number of women. This study seeks to characterize the contractile properties of late-pregnant myocardium. Methods and Results: Late Pregnancy (LP) Female Swiss-Webster mice were bred then studied at near term (Embryonic day 17-19) and compared to age-matched, non-pregnant (NP) controls. Individual cardiac myocytes were isolated using collagenase-based perfusion technique. Two-dimensional Surface Area measured in quiescent cells was elevated (p<.01) in LP myocytes (LPM) (3609± 132u 2 ) vs NP myocytes (NPM) (2736± 88u 2 ), and this increase was due to increases in both length (8.5%) and width (15.6%). Western Blot analysis showed a reduction in Ryanodine Receptor protein in LP, but no differences in L-type Ca Channel, SERCA or Phospholamban levels. Sarcomere length (light diffraction) and Ca 2+ transients (fluo-3) were measured at pacing rates of 1 Hz and at bath [Ca] of 2mM. Duration of twitch contraction was prolonged (p<.05) in LPM as measured by Time to 75% Recovery (.42 ± .02 vs .37 ±.01 sec in NPM) and Time to 90% recovery (.51 ± .02 vs .45 ± .02 sec in NPM). There were no differences in other contractile parameters measured or in the fluo-3 calcium transient properties. 10 -7 M Isoproterenol (ISO) was used to determine the responsiveness to adrenergic stimulation. ISO induced significantly enhanced contractility in both LPM and NPM, and the response was heightened in LPM such that the presence of ISO normalized the differences in the duration of twitch contraction between LPM and NPM. Conclusions: These results suggest that hypertrophied LPM have characteristics of both physiologic and pathologic hypertrophy including enhanced responsiveness to ISO and a prolonged relaxation phase. The prolongation of relaxation is not seen in physiologic hypertrophy induced by exercise and may contribute to the diastolic dysfunction reported in some pregnancies. Enhanced response to ISO suggests an increased cardiac reserve in LPM.

scholarly journals Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) and Cyclic ADP-Ribose (cADPR) Mediate Ca2+ Signaling in Cardiac Hypertrophy Induced by β-Adrenergic Stimulation

PLoS ONE ◽  
2016 ◽  
Vol 11 (3) ◽  
pp. e0149125 ◽  
Author(s):  
Rukhsana Gul ◽  
Dae-Ryoung Park ◽  
Asif Iqbal Shawl ◽  
Soo-Yeul Im ◽  
Tae-Sik Nam ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Nicotinic Acid ◽  
Adrenergic Stimulation ◽  
Cyclic Adp Ribose

scholarly journals Endogenously produced adiponectin protects cardiomyocytes from hypertrophy by a PPARγ-dependent autocrine mechanism

2010 ◽  
Vol 299 (3) ◽  
pp. H690-H698 ◽  
Author(s):  
Rajesh H. Amin ◽  
Suresh T. Mathews ◽  
Adebisi Alli ◽  
Todd Leff
Keyword(s):  
Gene Expression ◽  
Cardiac Hypertrophy ◽  
Signaling Pathway ◽  
Receptor Gene ◽  
Peroxisome Proliferator ◽  
Adrenergic Stimulation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Beneficial Effects ◽  
Ppar Γ ◽  
Culture Models

In experimental animal and cell culture models, activation of peroxisome proliferator-activated receptor (PPAR) γ in heart has been shown to have beneficial effects on cardiac function and cardiomyocyte physiology. The goal of this study was to identify the signaling pathway by which PPARγ activation protects cardiomyocytes from the deleterious effects of hypertrophic stimuli. In primary cardiomyocyte cultures, we found that genetic or pharmacological activation of PPARγ protected cells from cardiac hypertrophy induced by α-adrenergic stimulation. Examination of gene expression in these cells revealed a surprising increase in the expression of adiponectin in cardiomyocytes and secretion of the high-molecular-weight form of the hormone into media. Using RNAi to block PPARγ-induced adiponectin production or adiponectin receptor gene expression, we found that the PPARγ-mediated anti-hypertrophic effect required cardiomyocyte-produced adiponectin, as well as an intact adiponectin signaling pathway. Furthermore, mice expressing constitutive-active PPARγ and cardiomyocyte specific adiponectin expression were protected from high-fat diet-induced cardiac hypertrophy and remodeling. These findings demonstrate that functional adiponectin hormone can be produced from the heart and raise the possibility that beneficial effects of PPARγ activation in heart could be due in part to local production of adiponectin that acts on cardiomyocytes in an autocrine manner.

Abstract 411: Absence of Sexual Dimorphism in Isoproterenol-induced Cardiac Dysfunction in C57BL/6 Mice

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Marianne K Grant ◽  
Davis Seelig ◽  
Ibrahim Abdelgawad ◽  
Beshay Zordoky
Keyword(s):  
Cardiac Hypertrophy ◽  
Sex Hormones ◽  
Cardiac Dysfunction ◽  
Cardiovascular Effects ◽  
Current Work ◽  
Similar Degree ◽  
Adrenergic Stimulation ◽  
Male And Female ◽  
Female Mice ◽  
Significant Difference

Sex-related differences in cardiovascular diseases are complex and highly context-dependent. The objective of this work was to comprehensively determine key sex differences in the response to acute and chronic adrenergic stimulation in C57Bl/6 mice. In the current work, there was no statistically significant difference in key echocardiographic parameters between male and female C57Bl/6 mice in response to acute adrenergic stimulation (a single sub-cutaneous dose of isoproterenol 10 mg/kg). After chronic adrenergic administration (sub-cutaneous injections of isoproterenol 10 mg/kg/day for 14 days), there was similar degree of cardiac dysfunction, cardiac hypertrophy, and myocardial fibrosis in male and female mice. Similarly, chronic isoproterenol administration induced hypertrophic and fibrotic genes in hearts of male and female mice to the same extent. Intriguingly, gonadectomy of male and female mice did not have a significant impact on isoproterenol-induced cardiac dysfunction as compared to sham-operated animals. In conclusion, the current work demonstrated lack of sex-related differences in isoproterenol-induced cardiac hypertrophy, dysfunction, and fibrosis in C57Bl/6 mice. This study challenges the conventional dogma of the detrimental cardiovascular effects of male sex hormones and the beneficial effects of female sex hormones.

scholarly journals Orphan Nuclear Receptor Nur77 Inhibits Cardiac Hypertrophic Response to Beta-Adrenergic Stimulation

2015 ◽  
Vol 35 (19) ◽  
pp. 3312-3323 ◽  
Author(s):  
Guijun Yan ◽  
Ni Zhu ◽  
Shengdong Huang ◽  
Bing Yi ◽  
Xiying Shang ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Nuclear Receptor ◽  
Nuclear Translocation ◽  
Negative Regulator ◽  
Immunofluorescent Staining ◽  
Dependent Manner ◽  
Orphan Nuclear Receptor ◽  
Adrenergic Stimulation ◽  
Beta Adrenergic ◽  
Intramyocardial Injection

The orphan nuclear receptor Nur77 plays critical roles in cardiovascular diseases, and its expression is markedly induced in the heart after beta-adrenergic receptor (β-AR) activation. However, the functional significance of Nur77 in β-AR signaling in the heart remains unclear. By using Northern blot, Western blot, and immunofluorescent staining assays, we showed that Nur77 expression was markedly upregulated in cardiomyocytes in response to multiple hypertrophic stimuli, including isoproterenol (ISO), phenylephrine (PE), and endothelin-1 (ET-1). In a time- and dose-dependent manner, ISO increases Nur77 expression in the nuclei of cardiomyocytes. Overexpression of Nur77 markedly inhibited ISO-induced cardiac hypertrophy by inducing nuclear translocation of Nur77 in cardiomyocytes. Furthermore, cardiac overexpression of Nur77 by intramyocardial injection of Ad-Nur77 substantially inhibited cardiac hypertrophy and ameliorated cardiac dysfunction after chronic infusion of ISO in mice. Mechanistically, we demonstrated that Nur77 functionally interacts with NFATc3 and GATA4 and inhibits their transcriptional activities, which are critical for the development of cardiac hypertrophy. These results demonstrate for the first time that Nur77 is a novel negative regulator for the β-AR-induced cardiac hypertrophy through inhibiting the NFATc3 and GATA4 transcriptional pathways. Targeting Nur77 may represent a potentially novel therapeutic strategy for preventing cardiac hypertrophy and heart failure.

Predominant activation of endothelin-dependent cardiac hypertrophy by norepinephrine in rat left ventricle

2002 ◽  
Vol 282 (5) ◽  
pp. R1389-R1394 ◽  
Author(s):  
Lutz Moser ◽  
Jörg Faulhaber ◽  
Rudolf J. Wiesner ◽  
Heimo Ehmke
Keyword(s):  
Gene Expression ◽  
Left Ventricle ◽  
Aortic Stenosis ◽  
Cardiac Hypertrophy ◽  
Left Ventricular ◽  
Receptor Blockade ◽  
Ang Ii ◽  
Adrenergic Stimulation ◽  
Adult Rats ◽  
Primary Stimulus

Locally released endothelin (ET)-1 has been recently identified as an important mediator of cardiac hypertrophy. It is still unclear, however, which primary stimulus specifically activates ET-dependent signaling pathways. We therefore examined in adult rats ( n = 51) the effects of a selective ETA receptor antagonist in experimental models of cardiac hypertrophy, in which myocardial growth is predominantly initiated by a single primary stimulus. Rats were exposed to mechanical overload (ascending aortic stenosis), increased levels of circulating ANG II (ANG II infusion combined with hydralazine), or adrenergic stimulation (infusion of norepinephrine in a subpressor dose) for 7 days. All experimental treatments significantly increased left ventricular weight/body weight ratios compared with untreated rats, whereas systolic left ventricular peak pressure was increased only after ascending aortic stenosis. ETA receptor blockade exclusively reduced norepinephrine-induced cardiac hypertrophy and atrial natriuretic peptide gene expression. Blood pressure levels and heart rates remained unaffected during ETA receptor blockade in all experimental groups. These data indicate that in rat left ventricle, the ET-dependent signaling pathway leading to early development of cardiac hypertrophy and fetal gene expression is primarily activated by norepinephrine.

Abstract 1224: Rock1 Deletion Prevents Cardiac Dilation And Improves Contractile Function In Pathological Cardiac Hypertrophy

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Jianjian Shi ◽  
Yi-Wei Zhang ◽  
Gerald W Dorn ◽  
Lei Wei
Keyword(s):  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Cardiac Fibrosis ◽  
Contractile Function ◽  
Left Ventricular ◽  
Cardiomyocyte Hypertrophy ◽  
Molecular Defect ◽  
Contractile Dysfunction ◽  
Adrenergic Stimulation ◽  
Compensatory Response

The development of left ventricular cardiomyocyte hypertrophy in response to increased hemodynamic load and neurohormonal stress is initially a compensatory response. However, persistent stress eventually leads to dilated heart failure, which is a common cause of heart failure in human hypertensive and valvular heart disease. We have recently reported that ROCK1 homozygous knockout mice exhibited reduced cardiac fibrosis and cardiomyocyte apoptosis, while displayed a preserved compensatory hypertrophic response to pressure overload. Here, we tested effects of ROCK1 deficiency on cardiac hypertrophy, dilation, and dysfunction by using the transgenic Gαq mice which represent a well-characterized and highly relevant genetic mouse model of pathological hypertrophy and heart failure. We have shown that ROCK1 deletion prevented left ventricular dilation and contractile dysfunction in Gαq mice under basal condition. ROCK1 deletion also partially rescued bradycardia and improved contractile response to β-adrenergic stimulation in Gαq mice. Although the development of cardiomyocyte hypertrophy was not affected, ROCK1 deletion in Gαq mice resulted in a concentric hypertrophic phenotype associated with reduced induction of hypertrophic markers. Finally, ROCK1 deletion prevented down-regulation of type V adenylyl cyclase expression, which is a critical molecular defect contributing to the impaired β-adrenergic signaling in Gαq mice. The present study establishes for the first time a role for ROCK1 in cardiac dilation and contractile dysfunction.

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