Faculty Opinions recommendation of Disruption of coordinated cardiac hypertrophy and angiogenesis contributes to the transition to heart failure.

2006 ◽  
Author(s):  
Fabio Recchia
Keyword(s):  
Heart Failure ◽  
Cardiac Hypertrophy

scholarly journals Betulinic Acid Protects DOX-Triggered Cardiomyocyte Hypertrophy Response through the GATA-4/Calcineurin/NFAT Pathway

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 53
Author(s):  
Jung Joo Yoon ◽  
Chan Ok Son ◽  
Hye Yoom Kim ◽  
Byung Hyuk Han ◽  
Yun Jung Lee ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Natriuretic Peptide ◽  
Betulinic Acid ◽  
Cardiomyocyte Hypertrophy ◽  
Ros Generation ◽  
H9c2 Cells ◽  
Myosin Light Chain 2 ◽  
Cardiovascular Morbidity And Mortality

Cardiac hypertrophy is a major risk factor for heart failure and leads to cardiovascular morbidity and mortality. Doxorubicin (DOX) is regarded as one of the most potent anthracycline antibiotic agents; however, its clinical usage has some limitations because it has serious cardiotoxic side effects such as dilated cardiomyopathy and congestive heart failure. Betulinic acid (BA) is a pentacyclic-cyclic lupane-type triterpene that has been reported to have anti-bacterial, anti-inflammatory, anti-vascular neogenesis, and anti-fibrotic effects. However, there is no study about its direct effect on DOX induced cardiac hypertrophy and apoptosis. The present study aims to investigate the effect of BA on DOX-induced cardiomyocyte hypertrophy and apoptosis in vitro in H9c2 cells. The H9c2 cells were stimulated with DOX (1 µM) in the presence or absence of BA (0.1–1 μM) and incubated for 24 h. The results of the present study indicated that DOX induces the increase cell surface area and the upregulation of hypertrophy markers including atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), beta-myosin heavy chain (β-MHC), and Myosin Light Chain-2 (MLC2) in H9c2 cells. However, the pathological hypertrophic responses were downregulated after BA treatment. Moreover, phosphorylation of JNK, ERK, and p38 in DOX treated H9c2 cells was blocked by BA. As a result of measuring the change in ROS generation using DCF-DA, BA significantly inhibited DOX-induced the production of intracellular reactive oxygen species (ROS) when BA was treated at a concentration of over 0.1 µM. DOX-induced activation of GATA-4 and calcineurin/NFAT-3 signaling pathway were remarkably improved by pre-treating of BA to H9c2 cells. In addition, BA treatment significantly reduced DOX-induced cell apoptosis and protein expression levels of Bax and cleaved caspase-3/-9, while the expression of Bcl-2 was increased by BA. Therefore, BA can be a potential treatment for cardiomyocyte hypertrophy and apoptosis that lead to sudden heart failure.

scholarly journals Oxidative Stress as A Mechanism for Functional Alterations in Cardiac Hypertrophy and Heart Failure

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 931
Author(s):  
Anureet K. Shah ◽  
Sukhwinder K. Bhullar ◽  
Vijayan Elimban ◽  
Naranjan S. Dhalla
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Cardiac Remodeling ◽  
Cardiac Dysfunction ◽  
Critical Role ◽  
Pressure Overload ◽  
Hypertrophied Heart ◽  
Vasoactive Hormones

Although heart failure due to a wide variety of pathological stimuli including myocardial infarction, pressure overload and volume overload is associated with cardiac hypertrophy, the exact reasons for the transition of cardiac hypertrophy to heart failure are not well defined. Since circulating levels of several vasoactive hormones including catecholamines, angiotensin II, and endothelins are elevated under pathological conditions, it has been suggested that these vasoactive hormones may be involved in the development of both cardiac hypertrophy and heart failure. At initial stages of pathological stimuli, these hormones induce an increase in ventricular wall tension by acting through their respective receptor-mediated signal transduction systems and result in the development of cardiac hypertrophy. Some oxyradicals formed at initial stages are also involved in the redox-dependent activation of the hypertrophic process but these are rapidly removed by increased content of antioxidants in hypertrophied heart. In fact, cardiac hypertrophy is considered to be an adaptive process as it exhibits either normal or augmented cardiac function for maintaining cardiovascular homeostasis. However, exposure of a hypertrophied heart to elevated levels of circulating hormones due to pathological stimuli over a prolonged period results in cardiac dysfunction and development of heart failure involving a complex set of mechanisms. It has been demonstrated that different cardiovascular abnormalities such as functional hypoxia, metabolic derangements, uncoupling of mitochondrial electron transport, and inflammation produce oxidative stress in the hypertrophied failing hearts. In addition, oxidation of catecholamines by monoamine oxidase as well as NADPH oxidase activation by angiotensin II and endothelin promote the generation of oxidative stress during the prolonged period by these pathological stimuli. It is noteworthy that oxidative stress is known to activate metallomatrix proteases and degrade the extracellular matrix proteins for the induction of cardiac remodeling and heart dysfunction. Furthermore, oxidative stress has been shown to induce subcellular remodeling and Ca2+-handling abnormalities as well as loss of cardiomyocytes due to the development of apoptosis, necrosis, and fibrosis. These observations support the view that a low amount of oxyradical formation for a brief period may activate redox-sensitive mechanisms, which are associated with the development of cardiac hypertrophy. On the other hand, high levels of oxyradicals over a prolonged period may induce oxidative stress and cause Ca2+-handling defects as well as protease activation and thus play a critical role in the development of adverse cardiac remodeling and cardiac dysfunction as well as progression of heart failure.

scholarly journals Inhibition of the canonical Wnt signaling pathway by a β-catenin/CBP inhibitor prevents heart failure by ameliorating cardiac hypertrophy and fibrosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thanachai Methatham ◽  
Shota Tomida ◽  
Natsuka Kimura ◽  
Yasushi Imai ◽  
Kenichi Aizawa
Keyword(s):  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Left Ventricular ◽  
Cardiac Wall ◽  
Macrophage Marker ◽  
Glycolysis Pathway ◽  
Canonical Wnt ◽  
Macrophage Accumulation

AbstractIn heart failure (HF) caused by hypertension, the myocyte size increases, and the cardiac wall thickens. A low-molecular-weight compound called ICG001 impedes β-catenin-mediated gene transcription, thereby protecting both the heart and kidney. However, the HF-preventive mechanisms of ICG001 remain unclear. Hence, we investigated how ICG001 can prevent cardiac hypertrophy and fibrosis induced by transverse aortic constriction (TAC). Four weeks after TAC, ICG001 attenuated cardiac hypertrophy and fibrosis in the left ventricular wall. The TAC mice treated with ICG001 showed a decrease in the following: mRNA expression of brain natriuretic peptide (Bnp), Klf5, fibronectin, β-MHC, and β-catenin, number of cells expressing the macrophage marker CD68 shown in immunohistochemistry, and macrophage accumulation shown in flow cytometry. Moreover, ICG001 may mediate the substrates in the glycolysis pathway and the distinct alteration of oxidative stress during cardiac hypertrophy and HF. In conclusion, ICG001 is a potential drug that may prevent cardiac hypertrophy and fibrosis by regulating KLF5, immune activation, and the Wnt/β-catenin signaling pathway and inhibiting the inflammatory response involving macrophages.

scholarly journals Impairment of ultrastructure and cytoskeleton during progression of cardiac hypertrophy to heart failure

2010 ◽  
Vol 90 (4) ◽  
pp. 520-530 ◽  
Author(s):  
Anasuya Gupta ◽  
Sudhiranjan Gupta ◽  
David Young ◽  
Biswajit Das ◽  
James McMahon ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Hypertrophy

Abstract 037: Transient Cardiac Expression Of Constitutively Active G alpha Q Activates Renin-angiotensin System, Leading To Progressive Heart Failure And Ventricular Arrhythmias In Transgenic Mice

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Naoko Matsushita ◽  
Masamichi hirose ◽  
Yasuchika Taeishi ◽  
Satoshi Suzuki ◽  
Toshihide Kashihara ◽  
...  
Keyword(s):  
Heart Failure ◽  
Transgenic Mice ◽  
Cardiac Hypertrophy ◽  
Ventricular Arrhythmias ◽  
Renin Angiotensin System ◽  
Gene Expressions ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Progressive Heart Failure ◽  
Constitutively Active

Introduction: Transgenic mice with transient cardiac expression of constitutively active Galpha q (Gαq-TG) caused progressive heart failure and ventricular arrhythmias after the initiating stimulus becomes undetectable. However, the mechanisms are still unknown. Renin-angiotensin system plays a critical role in the development of cardiac hypertrophy and heart failure. We examined the effects of chronic administration of olmesartan on ventricular function, the number of premature ventricular contractions (PVC), and ventricular remodeling in Gαq-TG mice. Methods and Results: Olmesartan (1 mg/kg/day) or vehicle was chronically administered to Gαq-TG from 6 to 32 weeks of age, and all experiments were performed in mice at the age of 32 weeks. Chronic olmesartan treatment prevented the severe reduction of left ventricular fractional shortening and inhibited ventricular interstitial fibrosis and ventricular myocyte hypertrophy in Gαq-TG. Electrocardiogram demonstrated that premature ventricular contraction (PVC) was frequently (more than 20 beats/min) observed in 9 of 10 vehicle-treated Gαq-TG but in none of 10 olmesartan -treated Gαq-TG. The QT interval was significantly shorter in olmesartan-treated Gαq-TG than vehicle-treated Gαq-TG. CTGF, collagen type 1, ANP, BNP, and β-MHC gene expression was increased in vehicle-treated Gαq-TG. Olmesartan significantly decreased these gene expressions in Gαq-TG. Moreover, protein expressions of canonical transient receptor potential (TRPC) channels 3 and 6 increased in vehicle-treated Gαq-TG hearts. Olmesartan significantly decreased TRPC6 expressions in Gαq-TG. Angiotensin converting enzyme (ACE) 1 and 2 gene expressions were also increased in vehicle-treated Gαq-TG and was not decreased to the control level in olmesartan-treated Gαq-TG. Conclusions: These findings suggest that renin-angiotensin system has an important role in the development of cardiac hypertrophy and heart failure even if the initiating stimulus is different from the activation of renin-angiotensin system.

Abstract P320: The Gut Microbial Metabolite Butyrate Suppresses Cardiac Hypertrophy Via An Epigenetic Mechanism

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Masahiko Umei ◽  
Hiroshi Akazawa ◽  
Akiko Saga-Kamo ◽  
Hiroki Yagi ◽  
Qing Liu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Fatty Acid ◽  
Cardiac Hypertrophy ◽  
Short Chain Fatty Acid ◽  
Chain Fatty Acid ◽  
Epigenetic Mechanism ◽  
Neonatal Rat ◽  
Short Chain ◽  
Rat Cardiomyocytes ◽  
Hypertrophic Growth

Introduction: Short-chain fatty acids (SCFA) are one of the gut microbial metabolites that can influence host health and disease. We previously reported that gut dysbiosis is associated with heart failure, and that the proportion of butyrate-producing bacteria is decreased in the gut of patients with heart failure. Purpose: We investigated the molecular mechanism of butyrate in the development of cardiac hypertrophy. Methods and Results: Single-cell transcriptome analysis and co-expression network analysis revealed that G protein-coupled receptors for short-chain fatty acid receptors were not expressed in cardiomyocytes and that Olfr78 was expressed in vascular smooth muscle cells in the heart. On the other hand, treatment with butyrate inhibited ET1-induced and isoproterenol (ISO)-induced hypertrophic growth in cultured neonatal rat cardiomyocytes. Moreover, butyrate increased the acetylation levels of histone H3, suggesting the inhibitory effect of butyrate on HDAC. In addition, butyrate caused the degradation of HDAC2 and up-regulation of Inpp5f, encoding inositol polyphosphate-5-phosphatase f, leading to a significant decrease in the phosphorylation levels of Akt and glycogen synthase kinase 3β (GSK3β). Finally, intraperitoneal injection of butyrate inhibited ISO-induced cardiac hypertrophy in mice. These results suggest that butyrate protects against hypertrophic responses via suppression of the Akt-GSK3β pathway through HDAC inhibition. Conclusion: In the heart, there were no known short-chain fatty acid receptors in cardiomyocytes. However, butyrate was shown to have an epigenetic mechanism in suppressing effect on cardiomyocyte hypertrophy via suppression of HDAC2-Akt-GSK3β axis. Our results uncover a potential link between dysbiosis of intestinal microbiota and the development of cardiac hypertrophy.

MULTIPLE HEMANGIOMAS IN AN INFANT WITH CARDIAC HYPERTROPHY

PEDIATRICS ◽  
1965 ◽  
Vol 35 (1) ◽  
pp. 27-35
Author(s):  
Amiel G. Cooper ◽  
Robert P. Bolande
Keyword(s):  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Unknown Etiology ◽  
Developmental Abnormality ◽  
Tissue Destruction ◽  
Negro Female ◽  
Arteriovenous Shunts ◽  
Infantile Hemangioendothelioma ◽  
Cardiac Enlargement

A case of multiple benign hemangiomas in a 10-week-old Negro female is presented. At autopsy, numerous cutaneous and visceral sites of involvement were found. The hemangiomas are believed to arise from a multicentric developmental abnormality but appear capable of limited independent growth and tissue destruction. Postmortem angiograms demonstrate the existence of numerous arteriovenous shunts, which are believed responsible for the marked cardiac enlargement and early congestive heart failure in this case, as well as in previously reported cases of infantile hemangioendothelioma of the liver. Visceral hemangiomatosis should be considered as a possible extra-cardiac cause of infantile cardiac hypertrophy or failure of unknown etiology, especially in the infant with cutaneous hemangiomas. Angiographic techniques may be of help in the diagnosis and determination of extent of visceral hemangiomas.

HEMANGIOMA OF THE LIVER WITH HEART FAILURE: A CASE REPORT

PEDIATRICS ◽  
1954 ◽  
Vol 14 (2) ◽  
pp. 117-121
Author(s):  
ROBERT W. WINTERS ◽  
SAUL J. ROBINSON ◽  
GEORGE BATES
Keyword(s):  
Heart Failure ◽  
Congenital Heart Disease ◽  
Heart Disease ◽  
Case Report ◽  
Cardiac Hypertrophy ◽  
Cardiac Failure ◽  
Congenital Heart ◽  
Signs And Symptoms ◽  
Post Mortem ◽  
Great Vessels

A case of multiple hemangiomata of the liver is reported in an infant who presented signs and symptoms strongly suggesting congenital heart disease. The post mortem examination revealed no gross anomalies of the heart or great vessels, but did show a heart with cardiac hypertrophy. A mechanism to explain the cardiac failure in this case is discussed.

Abstract 3773: Myotrophin and the p53 Signaling Cascade in Cardiac Hypertrophy/Heart Failure

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Biswajit Das ◽  
David Young ◽  
Amit Vasanji ◽  
Sudhiranjan Gupta ◽  
Zoran Popovic ◽  
...  
Keyword(s):  
Heart Failure ◽  
Transgenic Mice ◽  
Cardiac Hypertrophy ◽  
Expression Profiles ◽  
Gene Array ◽  
Weight Ratio ◽  
Signaling Cascade ◽  
Mobility Shift ◽  
Transgenic Mouse Line ◽  
P53 Signaling

Myotrophin (Myo), a 12-kDa protein, stimulates myocyte growth and is a factor in initiating cardiac hypertrophy (CH). Cardiospecific overexpression of Myo in transgenic mice (Myo-Tg) induces hypertrophy that progresses to heart failure (HF). Oligonucleotide gene array revealed upregulation of a p53 homologue gene (EST- AI843106 ) in Myo-Tg mice during HF, indicating that p53 plays an important role during the transition of hypertrophy to HF. To dissect out the mechanisms of p53-mediated Myo-induced CH/HF, we developed a double-transgenic mouse line (p53 −/− /myo +/+ ) by crossing Myo-Tg mice with p53-null mice. The double transgenic mice showed a significant attenuation of cardiac mass compared to Myo-Tg mice (heart weight:body weight ratio; 5.2 ± 0.21 vs. 7.9 ± 0.58, p < 0.001) associated with improved cardiac function and downregulation of ANF expression, suggesting that hypertrophy induced by Myo overexpression is indeed mediated through p53. To elucidate the relationship between p53 and Myo-induced hypertrophy, we performed a Reverse-Transcription Real-Time PCR pathway array on heart tissues from p53 −/− /myo +/+ vs. Myo-Tg mice. A bioinformatic approach, Ingenuity Pathway Analysis TM (IPA), was used to analyze the selected up-/downregulated genes. The IPA network showed that among the up-/downregulated genes, Bcl2, Brca1, Cdkn1a and Myc occupy the nodal position, whereas E2f1 , Pmaip1 , Gadd45a and Pttg1 function as peripheral candidates. The expression profiles of some genes of the p53 pathway were validated by immunoblot analysis. Functional assignment of these selected candidate genes showed that Bcl2, E2f1 and FasL are related to CH/HF, but the function of Gadd45a, Pmaip1, and Vcan is still unknown. Apart from these p53 cascade members, we also found that other molecules (e.g., Jnk, Ras, NF-kB, Cyclin L, and Mek) may be involved in an intricate interplay to stimulate p53-mediated Myo-induced CH. Suppression of NF-kB activity (by electrophoresis mobility shift assay) in p53 −/− /myo +/+ mice compared to Myo-Tg mice indicated involvement of NF-kB, as predicted by IPA, in Myo/p53 cross-talk. Our data suggest that the p53 signaling cascade actively participates in progression of hypertrophy to HF, triggered by overexpression of myotrophin.

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