Physiological Versus Pathological Hypertrophy

1997 ◽  
pp. 145-158 ◽  
Author(s):  
Cesare Cuspidi ◽  
Laura Lonati ◽  
Lorena Sampieri ◽  
Gastone Leonetti ◽  
Alberto Zanchetti
Keyword(s):  
Pathological Hypertrophy

Metabolic impairment in response to early induction of C/EBPβ leads to compromised cardiac function during pathological hypertrophy

2020 ◽  
Vol 139 ◽  
pp. 148-163 ◽  
Author(s):  
Durba Banerjee ◽  
Ratul Datta Chaudhuri ◽  
Sougata Niyogi ◽  
Sumedha Roy Chowdhuri ◽  
Mousumi Poddar Sarkar ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Pathological Hypertrophy

Abstract 151: A Novel Role for DDiT4L in Regulation of mTOR and Autophagy in the Heart

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Bridget Simonson ◽  
Hannabeth Franchino ◽  
Ashley Knight ◽  
Anthony Rosenzweig ◽  
Saumya Das
Keyword(s):  
Heart Failure ◽  
Protein Expression ◽  
Glucose Deprivation ◽  
Mtor Signaling ◽  
Confocal Imaging ◽  
Negative Regulator ◽  
Neonatal Rat ◽  
Pathological Hypertrophy ◽  
Gene And Protein Expression ◽  
Physiological Hypertrophy

Introduction: DDiT4L is a known negative regulator of mTOR signaling in skeletal muscle; however its role in the heart is unknown. We have recently showed increased DDiT4L mRNA in a murine transgenic model of pathological but not physiological hypertrophy. Here we test the hypothesis that DDiT4L is a regulator of mTOR signaling in the heart and may play a role in pathological hypertrophy and heart failure. Methods: We investigated the regulation of DDiT4L in murine models of hypertrophy and in cultured neonatal rat ventricular cardiomyocytes (NRVMs). Loss and gain of function of DDiT4L in mTOR regulation and autophagy was investigated using confocal imaging, immunoblotting, and qRT-PCR in NRVMs. Results: DDiT4L gene and protein expression was increased four-fold in pressure overload hypertrophy (n = 4-6, p<0.001), but not in a swim model of physiological hypertrophy. DDiT4L gene expression also significantly increased in a genetic model of dilated cardiomyopathy model (n = 4, p<0.001). In NRVMs, DDiT4L was induced by cardiac stressors such as pathological stretch, hypoxia, and glucose deprivation (n = 3-5 in duplicate, p<0.05-0.01). Increased DDiT4L expression correlated with inhibition of mTOR signaling, and an increase in autophagy markers. siRNA ablation of DDiT4L revealed that inhibition of mTOR signaling by DDiT4L was necessary for glucose deprivation induced autophagy, as determined by imaging of GFP-LC3 autophagosomes (n = 3 in duplicate, p<0.01), and immunoblotting of autophagy markers. Conversely, adenoviral-driven overexpression of DDiT4L inhibited mTOR signaling and significantly increased basal autophagy (n = 3 in duplicate, p<0.05). In TAC mice, the increase in DDiT4L protein expression correlated to inhibition of mTOR signaling, increases in autophagy markers (p<0.01), and preceded the transition to LV dilation and HF. Conclusion: Our data suggests that DDiT4L expression is altered in diverse models of pathological hypertrophy and precedes the development of LV dilatation and overt heart failure. DDiT4L inhibition of mTOR and modulation of autophagy may play a role in the progression to heart failure. DDiT4L may represent a novel therapeutic target to prevent this transition.

scholarly journals Effect of lithium on ventricular remodelling in infarcted rats via the Akt/mTOR signalling pathways

2017 ◽  
Vol 37 (2) ◽  
Author(s):  
Tsung-Ming Lee ◽  
Shinn-Zong Lin ◽  
Nen-Chung Chang
Keyword(s):  
Interstitial Fibrosis ◽  
Lithium Treatment ◽  
Cardiac Contractility ◽  
Mammalian Target Of Rapamycin ◽  
Left Ventricular ◽  
Initiation Factor ◽  
Gene Expressions ◽  
Activated T Cells ◽  
Pathological Hypertrophy ◽  
Mtor Signalling

Activation of phosphoinositide 3-kinase (PI3K)/Akt signalling is the molecular pathway driving physiological hypertrophy. As lithium, a PI3K agonist, is highly toxic at regular doses, we assessed the effect of lithium at a lower dose on ventricular hypertrophy after myocardial infarction (MI). Male Wistar rats after induction of MI were randomized to either vehicle or lithium (1 mmol/kg per day) for 4 weeks. The dose of lithium led to a mean serum level of 0.39 mM, substantially lower than the therapeutic concentrations (0.8–1.2 mM). Infarction in the vehicle was characterized by pathological hypertrophy in the remote zone; histologically, by increased cardiomyocyte sizes, interstitial fibrosis and left ventricular dilatation; functionally, by impaired cardiac contractility; and molecularly, by an increase of p-extracellular-signal-regulated kinase (ERK) levels, nuclear factor of activated T cells (NFAT) activity, GATA4 expression and foetal gene expressions. Lithium administration mitigated pathological remodelling. Furthermore, lithium caused increased phosphorylation of eukaryotic initiation factor 4E binding protein 1 (p-4E-BP1), the downstream target of mammalian target of rapamycin (mTOR). Blockade of the Akt and mTOR signalling pathway with deguelin and rapamycin resulted in markedly diminished levels of p-4E-BP1, but not ERK. The present study demonstrated that chronic lithium treatment at low doses mitigates pathological hypertrophy through an Akt/mTOR dependent pathway.

scholarly journals Physiological activation of Akt by PHLPP1 deletion protects against pathological hypertrophy

2014 ◽  
Vol 105 (2) ◽  
pp. 160-170 ◽  
Author(s):  
Courtney Moc ◽  
Amy E. Taylor ◽  
Gino P. Chesini ◽  
Cristina M. Zambrano ◽  
Melissa S. Barlow ◽  
...  
Keyword(s):  
Pathological Hypertrophy

Endogenous intoxication in chronic pathology of pharynx in children

2021 ◽  
Vol 20 (3) ◽  
pp. 94-101
Author(s):  
T. A. Mashkova ◽  
◽  
I. I. Chirkova ◽  
O. N. Yamshchikov ◽  
I. Yu. Revyakin ◽  
...  
Keyword(s):  
Biological Fluids ◽  
The Body ◽  
Chronic Tonsillitis ◽  
Palatine Tonsils ◽  
Immunological Markers ◽  
Decay Products ◽  
Endogenous Intoxication ◽  
Pathological Hypertrophy ◽  
Chronic Adenoiditis ◽  
Pharyngeal Tonsil

A review of scientific Russian and foreign articles devoted to the development of endogenous intoxication in chronic inflammatory pathology of the lymphoepithelial pharyngeal ring is carried out. Chronic tonsillitis and adenoiditis in children are one of the unsolved issues in otorhinolaryngology. Chronic tonsillitis is a chronic inflammation of the palatine tonsils characterized by recurrent exacerbations in the form of tonsillitis and a general toxic-allergic reaction. Adenoid vegetation is a pathological hypertrophy of the pharyngeal tonsil. Chronic adenoiditis is a chronic polyetiologic disease, which is based on a violation of the physiological immune processes of the pharyngeal tonsil. In children, one cannot talk about an isolated inflammation of the pharyngeal tonsil, since as a result of exposure to antigens, an immune response arises, which involves all structures of the lymphoepithelial pharyngeal ring in the process, therefore some authors distinguish the term «adenotonsillitis». With pronounced activation of microflora in the nasopharynx and oropharynx, the body’s resistance to pathogenic microorganisms decreases, as a result of which decay products and toxins damage the vascular endothelium, disrupt their permeability and, penetrating through the epithelial barrier, contribute to the development of chronic intoxication and sensitization of the body. Endogenous intoxication is a polyetiologic and polypathogenetic syndrome characterized by the accumulation of endogenous toxins in tissues and biological fluids. Diagnostics of the endogenous intoxication severity includes a number of clinical and laboratory indicators and immunological markers. But, despite the constant improvement of the research methods, the issue of endotoxicosis diagnosis in chronic tonsillitis and adenoiditis remains insufficiently studied. As a result of the inadequate diagnosis, there is often a simultaneous removal of the pharyngeal and palatine tonsils, which in turn can lead to irreversible consequences.

scholarly journals Vitamin A as a Transcriptional Regulator of Cardiovascular Disease

Hearts ◽  
2020 ◽  
Vol 1 (2) ◽  
pp. 126-145
Author(s):  
Robert S. Leigh ◽  
Bogac L. Kaynak
Keyword(s):  
Cardiovascular Disease ◽  
Vitamin A ◽  
Nutrient Deficiency ◽  
Cardiac Regeneration ◽  
Pathological Hypertrophy ◽  
Hematological Cancers ◽  
Pharmacological Studies ◽  
Hypertrophy Of The Heart ◽  
Exogenous Delivery ◽  
The Relationship

Vitamin A is a micronutrient and signaling molecule that regulates transcription, cellular differentiation, and organ homeostasis. Additionally, metabolites of Vitamin A are utilized as differentiation agents in the treatment of hematological cancers and skin disorders, necessitating further study into the effects of both nutrient deficiency and the exogenous delivery of Vitamin A and its metabolites on cardiovascular phenotypes. Though vitamin A/retinoids are well-known regulators of cardiac formation, recent evidence has emerged that supports their role as regulators of cardiac regeneration, postnatal cardiac function, and cardiovascular disease progression. We here review findings from genetic and pharmacological studies describing the regulation of both myocyte- and vascular-driven cardiac phenotypes by vitamin A signaling. We identify the relationship between retinoids and maladaptive processes during the pathological hypertrophy of the heart, with a focus on the activation of neurohormonal signaling and fetal transcription factors (Gata4, Tbx5). Finally, we assess how this information might be leveraged to develop novel therapeutic avenues.

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.

Expression of lipogenic genes is upregulated in the heart with exercise training-induced but not pressure overload-induced left ventricular hypertrophy

2013 ◽  
Vol 304 (12) ◽  
pp. E1348-E1358 ◽  
Author(s):  
Pawel Dobrzyn ◽  
Aleksandra Pyrkowska ◽  
Monika K. Duda ◽  
Tomasz Bednarski ◽  
Michal Maczewski ◽  
...  
Keyword(s):  
Regulatory Element ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Hormone Sensitive Lipase ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cardiac Lipid ◽  
Protein Levels ◽  
Lipogenic Genes ◽  
Pathological Hypertrophy

Cardiac hypertrophy is accompanied by molecular remodeling that affects different cellular pathways, including fatty acid (FA) utilization. In the present study, we show that cardiac lipid metabolism is differentially regulated in response to physiological (endurance training) and pathological [abdominal aortic banding (AAB)] hypertrophic stimuli. Physiological hypertrophy was accompanied by an increased expression of lipogenic genes and the activation of sterol regulatory element-binding protein-1c and Akt signaling. Additionally, FA oxidation pathways regulated by AMP-activated protein kinase (AMPK) and peroxisome proliferator activated receptor-α (PPARα) were induced in trained hearts. Cardiac lipid content was not changed by physiological stimulation, underlining balanced lipid utilization in the trained heart. Moreover, pathological hypertrophy induced the AMPK-regulated oxidative pathway, whereas PPARα and expression of its downstream targets, i.e., acyl-CoA oxidase and carnitine palmitoyltransferase I, were not affected by AAB. In contrast, pathological hypertrophy leads to cardiac triglyceride (TG) and diacylglycerol (DAG) accumulation, although the expression of lipogenic genes and the levels of FA transport proteins (CD36 and FATP) were not changed or reduced compared with the sham group. A possible explanation for this phenomenon is a decrease in lipolysis, as evidenced by the increased content of adipose triglyceride lipase inhibitor G0S2, the increased phosphorylation of hormone-sensitive lipase at Ser565, and the decreased protein levels of DAG lipase that attenuate TG and DAG contents. The increased TG and DAG accumulation observed in AAB-induced hypertrophy might have lipotoxic effects, thereby predisposing to cardiomyopathy and heart failure in the future.

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