Pathological vs. physiological cardiac hypertrophy

Kavazis, Andreas N.

doi:10.1113/jp271161

Cited by 14 publications

(11 citation statements)

References 4 publications

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“…Indeed, pathological cardiac hypertrophy usually progresses into heart failure and is a major cause of death in young adults in developed countries. In contrast, physiological hypertrophy, as caused by pregnancy or exercise, is beneficial ( 1 – 4 ).…”

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confidence: 99%

Quantitative Non-canonical Amino Acid Tagging (QuaNCAT) Proteomics Identifies Distinct Patterns of Protein Synthesis Rapidly Induced by Hypertrophic Agents in Cardiomyocytes, Revealing New Aspects of Metabolic Remodeling

Kenney

Manousopoulou

et al. 2016

Molecular & Cellular Proteomics

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Cardiomyocytes undergo growth and remodeling in response to specific pathological or physiological conditions. In the former, myocardial growth is a risk factor for cardiac failure and faster protein synthesis is a major factor driving cardiomyocyte growth. Our goal was to quantify the rapid effects of different pro-hypertrophic stimuli on the synthesis of specific proteins in ARVC and to determine whether such effects are caused by alterations on mRNA abundance or the translation of specific mRNAs. Cardiomyocytes have very low rates of protein synthesis, posing a challenging problem in terms of studying changes in the synthesis of specific proteins, which also applies to other nondividing primary cells. To study the rates of accumulation of specific proteins in these cells, we developed an optimized version of the Quantitative Noncanonical Amino acid Tagging LC/MS proteomic method to label and selectively enrich newly synthesized proteins in these primary cells while eliminating the suppressive effects of pre-existing and highly abundant nonisotope-tagged polypeptides. Our data revealed that a classical pathologic (phenylephrine; PE) and the recently identified insulin stimulus that also contributes to the development of pathological cardiac hypertrophy (insulin), both increased the synthesis of proteins involved in, e.g. glycolysis, the Krebs cycle and beta-oxidation, and sarcomeric components. However, insulin increased synthesis of many metabolic enzymes to a greater extent than PE. Using a novel validation method, we confirmed that synthesis of selected candidates is indeed up-regulated by PE and insulin. Synthesis of all proteins studied was up-regulated by signaling through mammalian target of rapamycin complex 1 without changes in their mRNA levels, showing the key importance of translational control in the rapid effects of hypertrophic stimuli. Expression of PKM2 was up-regulated in rat hearts following TAC. This isoform possesses specific regulatory properties, so this finding indicates it may be involved in metabolic remodeling and also serve as a novel candidate biomarker. Levels of translation factor eEF1 also increased during TAC, likely contributing to faster cell mass accumulation. Interestingly those two candidates were not up-regulated in pregnancy or exercise induced CH, indicating PKM2 and eEF1 were pathological CH specific markers. We anticipate that the methodologies described here will be valuable for other researchers studying protein synthesis in primary cells.

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confidence: 99%

Quantitative Non-canonical Amino Acid Tagging (QuaNCAT) Proteomics Identifies Distinct Patterns of Protein Synthesis Rapidly Induced by Hypertrophic Agents in Cardiomyocytes, Revealing New Aspects of Metabolic Remodeling

Kenney

Manousopoulou

et al. 2016

Molecular & Cellular Proteomics

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“…The changes that occur are in the form of hypertrophy in the heart muscle. In general, pathological cardiac hypertrophy characterized by the thickening of the heart muscle, a decrease in the size of the chambers of the heart, and a reduced capacity of the heart to pump blood to the tissues and organs around the body [16].…”

Section: Resultsmentioning

confidence: 99%

Effect of Simvastatin on Histopathology of the Heart After 5/6 Subtotal Nephrectomy

Cahyawati

2019

Int J App Pharm

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Objective: This study aims to assess the condition of cardiac histopathology through hematoxylin-eosin staining in 5/6 subtotal nephrectomyconditions.Methods: Fifteen male Swiss mice aged 3–5 months will be grouped into 3 treatment groups, namely the nephrectomy group (JSN, n=5), shamoperation (JSO, n=5), and simvastatin 20 mg/kg body weight (JSIM, n=5). The histopathology of the heart will be assessed blindly. Severity is assessedbased on scoring using a scale (−) no damage, (+) mild, (++) medium, and (+++) heavy. Assessment of severity refers to the irregularity of the heartmuscle, increased amount of connective tissue, myofibril hypertrophy, myofibril swelling, sarcoplasmic fragmentation, sarcoplasmic vacuolization,bleeding in a myofibril, myofibril degeneration, cardiomyocyte damage, and the presence of acidophilic cytoplasm.Results: The results showed no morphological changes in heart muscle tissue in the JSO group except for fragmentation and vacuolization in minimalamounts of sarcoplasm (+), whereas in the JSN and JSIM groups, there was moderate damage to sarcoplasm (++) and minimal changes in myofibrils(hypertrophy and bleeding) (+). The JSN group also found severe damage (+++) to the irregularity of the heart muscle, whereas in JSIM, only moderatedamage was found (++) to the irregularity of the heart muscle.Conclusion: Simvastatin seems to be able to correct the irregularity of the heart muscle in the condition of 5/6 subtotal nephrectomy.

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“…Although the enlargement of the heart by pathological and physiological hypertrophy has similar morphological appearances, the outcomes of the two types of hypertrophy are strikingly different. 18,19) Exercise-induced physiological hypertrophy leads to a considerable improvement in the quality of life, whereas pressure overload-induced pathological hypertrophy is associated with the progressive deterioration of heart functions. Pre-vious reports had proved that aerobic exercise training induced physiological cardiac hypertrophy accompanied the differential expression of the miRNAs.…”

Section: Discussionmentioning

confidence: 99%

Screening and Function Analysis of MicroRNAs Involved in Exercise Preconditioning-Attenuating Pathological Cardiac Hypertrophy

Yang

You

et al. 2018

Int. Heart J.

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Exercise preconditioning (EP) attenuates pathological cardiac hypertrophy by increasing the functional capacity of the cardiovascular system; however, the underlying molecular mechanisms remain unclear. MicroRNAs (miRNAs) play important roles in various physiological and pathological processes by regulating the expression of the targeted gene. In this study, we aimed to screen the miRNAs involved in EP-attenuating pathological cardiac hypertrophy. The histological and echocardiographic parameters assessment showed that pathological cardiac hypertrophy induced by transverse aortic constriction (TAC) was significantly alleviated in EP treated rats. The left ventricular tissues (n = 3) from Sham, TAC and EP + TAC groups were subjected to small RNA deep sequencing. A total of 570 known mature miRNAs and 530 putative novel miRNAs were detected. DEGseq analysis showed that there were 37 and 88 differentially expressed miRNAs in the comparisons of TAC versus Sham and EP + TAC versus TAC, respectively. Among them, EP treatment could relieve the expression changes of 32 miRNAs, which were supposed to be involved in EP-attenuating pathological cardiac hypertrophy. After miRNAs target genes prediction by miRDB algorithm, pathway analysis showed that the most frequently represented pathways were involved in Calcium signaling pathway and MAPK signaling pathway. The results would provide valuable clues to finding therapeutic targets for the treatment of pathological cardiac hypertrophy.

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Pathological vs. physiological cardiac hypertrophy

Cited by 14 publications

References 4 publications

Quantitative Non-canonical Amino Acid Tagging (QuaNCAT) Proteomics Identifies Distinct Patterns of Protein Synthesis Rapidly Induced by Hypertrophic Agents in Cardiomyocytes, Revealing New Aspects of Metabolic Remodeling

Quantitative Non-canonical Amino Acid Tagging (QuaNCAT) Proteomics Identifies Distinct Patterns of Protein Synthesis Rapidly Induced by Hypertrophic Agents in Cardiomyocytes, Revealing New Aspects of Metabolic Remodeling

Effect of Simvastatin on Histopathology of the Heart After 5/6 Subtotal Nephrectomy

Screening and Function Analysis of MicroRNAs Involved in Exercise Preconditioning-Attenuating Pathological Cardiac Hypertrophy

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