• 한국식품영양과학회지
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• 제32권5호
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• pp.700-705
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• 2003

배에서 추출된 pectin과 사과에서 추출된 pectin의 3주간 투여가 2K1C 고혈압 흰쥐의 일간 혈압 변화, 혈장 renin, ANP 변화 및 cardiac hypertrophy 변화를 관찰한 결과 다음과 같은 결론을 얻었다. 일간 혈압변화에서 대조군에 비하여 AP-A군의 15일째에 유의한 감소를 보였고, 19일째에 한계적으로 유의한 감소를 나타내었으며, AP-B군의 8일째와 15일째에 유의한 감소를 나타내었으며, AP-C군의 15일째에 한계적으로 유의한 감소를 나타내었다. 또한 대조군에 비하여 PP-A군은 모든 기간 동안 유의성을 나타내지 않았으며, PP-B군의 8일째와 15일째에 유의한 감소를 나타내었으며, PP-C군의 15일째에 유의한 감소를 나타내었다. 혈장 renin변화에 있어서 대조군에 비하여 apple pectin이 투여된 군에서는 모두 유의한 변화가 없었으며, pear pectin이 투여 된 PP-B군에서 한계적으로 유의한 감소를 나타내었다. 혈장 ANP 변화에 있어서 대조군에 비하여 apple pectin이 투여된 군에서는 모두 유의한 변화가 없었으며, pear pectin이 투여된 PP-B군에서 유의한 증가를 나타내었다. Cardiac hypertrophy 변화에 있어서 대조군에 비하여 apple pectin이 투여된 군에서는 모두 유의한 변화가 없었으며, pear pectin이 투여된 PP-C군에서 유의한 감소를 나타내었다.

• BMB Reports
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• 제50권4호
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• pp.208-213
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• 2017

Vascular endothelial growth factor (VEGF) is an essential cytokine that has functions in the formation of new blood vessels and regression of cardiac hypertrophy. VEGF/VEGF-receptor-1 (VEGFR1) signaling plays a key role in the regression of cardiac hypertrophy, whereas VEGF/VEGFR2 signaling leads to cardiac hypertrophy. In this study, we identified the prohypertrophic role of miR-374 using neonatal rat ventricular myocytes (NRVMs). Our results showed that overexpression of miR-374 activated G protein-coupled receptor-mediated prohypertrophic pathways by the inhibition of VEGFR1-dependent regression pathways. Luciferase assays revealed that miR-374 could directly target the 3'-untranslated regions of VEGFR1 and cGMP-dependent protein kinase-1. Collectively, these findings demonstrated that miR-374 was a novel pro-hypertrophic microRNA functioning to suppress the VEGFR1-mediated regression pathway.

• 대한수의학회지
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• 제44권1호
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• pp.7-13
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• 2004

Severe hypertension (>180 mmHg) develops in spontaneously hypertensive rats (SHR) after 12 wk-old; however, it is not clear whether what kinds of molecular mechanism leads to altered cardiac performance following developmental stages in SHR. Also, although the effect of calcineurin (Cn) to promote cardiomyocyte hypertrophy in vivo and in vitro is established, its overall necessity as a hypertrophic mediator is currently an area of ongoing debate. Thus, we have examined i) body weight and blood pressure, ii) differences of expression and distribution of signaling molecules such as Cn, protein kinase B/Akt (PKB/Akt), and extracellular signal-regulated kinase (ERK) between SHR and their age-matched control Wistar-Kyoto (WKY) rats following developmental stages. In 16 wk-old SHR compared with WKY, 2-dimentional echocardiography showed cardiac enlargement and hypertrophy of left ventricle, significantly. Taken together, we suggest that Cn is associated with hereditary cardiac hypertrophy, the process being related to the molecular signaling mechanisms involving PKB/Akt and ERK.

• Molecules and Cells
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• 제44권7호
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• pp.500-516
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• 2021

Cardiac hypertrophic signaling cascades resulting in heart failure diseases are mediated by protein phosphorylation. Recent developments in mass spectrometry-based phosphoproteomics have led to the identification of thousands of differentially phosphorylated proteins and their phosphorylation sites. However, functional studies of these differentially phosphorylated proteins have not been conducted in a large-scale or high-throughput manner due to a lack of methods capable of revealing the functional relevance of each phosphorylation site. In this study, an integrated approach combining quantitative phosphoproteomics and cell-based functional screening using phosphorylation competition peptides was developed. A pathological cardiac hypertrophy model, junctate-1 transgenic mice and control mice, were analyzed using label-free quantitative phosphoproteomics to identify differentially phosphorylated proteins and sites. A cell-based functional assay system measuring hypertrophic cell growth of neonatal rat ventricle cardiomyocytes (NRVMs) following phenylephrine treatment was applied, and changes in phosphorylation of individual differentially phosphorylated sites were induced by incorporation of phosphorylation competition peptides conjugated with cell-penetrating peptides. Cell-based functional screening against 18 selected phosphorylation sites identified three phosphorylation sites (Ser-98, Ser-179 of Ldb3, and Ser-1146 of palladin) displaying near-complete inhibition of cardiac hypertrophic growth of NRVMs. Changes in phosphorylation levels of Ser-98 and Ser-179 in Ldb3 were further confirmed in NRVMs and other pathological/physiological hypertrophy models, including transverse aortic constriction and swimming models, using site-specific phospho-antibodies. Our integrated approach can be used to identify functionally important phosphorylation sites among differentially phosphorylated sites, and unlike conventional approaches, it is easily applicable for large-scale and/or high-throughput analyses.

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 2003년도 정기총회 및 학술발표회
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• pp.52-52
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• 2003

Junctate is a newly identified integral ER/SR membrane $Ca^{2+}$ binding protein, which is an alternative splicing form of the same gene generating aspartyl $\square$-hydroxylase and junctin. To elucidate the functional role of junctate in heart, transgenic (TG) mice overexpressing mouse cardiac junctate-1 under the control of mouse $\square$$^{~}$ myosin heavy chain promoter were generated. Overexpression of junctate in mouse heart resulted in cardiac hypertrophy, increased fibrosis, bradycardia, arrhythmias and impaired contractility. Overexpression of junctate also led to down-regulation of SERCA2, calsequestrin, calreticulin and RyR, but to up-regulation of NCX and PMCA. The SR $Ca^{2+}$ content decreased and the L-type $Ca^{2+}$ current density and the action potential durations increased in TG cardiomyocytes, which could be the cause for the bradycardia in TG heart. The present work has provided an important example of pathogenesis leading to cardiac hypertrophy and arrhythmia, which was caused by impaired $Ca^{2+}$ handling by overexpression of junctate in heart.n heart.

• Clinical and Experimental Pediatrics
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• 제52권7호
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• pp.752-755
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• 2009

It is well known that hemodynamic load is one of the most important determinants of cardiac structure and function. Circadian variations in blood pressure (BP) are usually accompanied by consensual changes in peripheral resistance and/or cardiac output. In recent years, reduction in circadian variations in BP and, in particular, loss of nocturnal decline of BP were observed in hypertensive patients with left ventricular hypertrophy (LVH). The patients with only a slight or no loss of nocturnal decline of BP were considered "non-dippers". Regression of LVH was observed after prolonged antihypertensive therapy. Restoration of the circadian rhythm of BP was also observed. However, the classification of patients into "dippers" and "non-dippers" is arbitrary and poorly standardized and repeatable, and in the recent studies, most hypertensive patients with LVH were "dippers". Therefore, we should be particularly cautious about the conclusions drawn using this index. On the other hand, reduced activity of low-pressure cardiopulmonary baroreceptors and impaired day-to-night modulation of autonomic nervous system activity were observed in patients with only LVH. Therefore, alterations in cardiac structure may impair BP modulation. On the other hand, the reverse can also be trueprimary alterations in BP modulation, through a persistently elevated afterload, can increase cardiac mass. Thus, the interrelationship between cardiac structure and BP modulation is complex. Hence, new and more specific methods of evaluating circadian changes in BP are needed to better clarify the abovementioned reciprocal influences.

• The Korean Journal of Physiology and Pharmacology
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• 제5권5호
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• pp.413-421
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• 2001

An impaired smooth muscle cell (SMC) relaxation of coronary artery by alteration of $K^+$ channels would be the most potential explanation for reduced coronary reserve in left ventricular hypertrophy (LVH), however, this possibility has not been investigated. We performed morphometrical analysis of the coronary artery under electron microscopy and measured $Ca^{2+}-activated\;K\;(K_{Ca})$ currents and delayed rectifier K $(K_{dr})$ currents by whole-cell and inside-out patch-clamp technique in single coronary arterial SMCs from rabbits subjected to isoprenaline-induced cardiac hypertrophy. Coronary arterial SMCs underwent significant changes in ultrastructure. The unitary current amplitude and the open-state probability of $K_{Ca}$ channel were significantly reduced in hypertrophy without open-time and closed-time kinetic. The concentration-response curve of $K_{Ca}$ channel to $Ca^{2+}$ is shifted to the right in hypertrophy. The reduction in the mean single channel current and increase in the open channel noise of $K_{Ca}$ channel by TEA were more sensitive in hypertrophy. $K_{dr}$ current density is significantly reduced in hypertrophy without activation and inactivation kinetics. The sensitivity of $K_{dr}$ current on 4-AP is significantly increased in hypertrophy. This is the first study to report evidence for alterations of $K_{Ca}$ channels and $K_{dr}$ channels in coronary SMCs with LVH. The findings may provide some insight into mechanism of the reduced coronary reserve in LVH.

• Reproductive and Developmental Biology
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• 제35권2호
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• pp.159-165
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• 2011

To explore the role of histone deactylase (HDAC) activation in an in vivo model of hypertrophy, we studied the effects of Trichostatin A (TSA). TSA subjected to thoracic aortic banding (TAB)-induced pressure stress in mice. In histological observations, TAB in treated mice showed a significant hypertrophic response, whereas the sham operation remained nearly normal structure with partially blunted hypertrophy. TSA treatment had no effect (measured as HW/BW) on sham-operated animals. TAB animals treated with vehicle manifested a robust ~50% hypertrophic response (p<0.05 vs sham). TAB mice treated with 2 mg/kg/day TSA manifested a blunted growth responses, which was significantly diminished (p<0.05) compared with vehicle-treated TAB mice. TAB mice treated with a lower dose of TSA (0.5 mg/kg/day) manifested a similar blunting of hypertrophic growth (~25% increase in heart mass). Furthermore, to determine activity duration of TSA in vitro, 1 nM TSA was added to H9c2 cells. Histone acetylation was initiated at 4 hr after treatment, and it was peak up to 18 hr, then followed by significantly reduced to 30 hr. We also analyzed the expression of p53 following TSA treatment, wherein p53 expression was elevated at 4 hr, and it was maintained to 24 hr after treatment. ERK was activated at 8 hr, and maintained till 30 hr after treatment suggesting an intracellular signaling interaction between TSA and p53 expression Taken together, it is suggested that HDAC activation is required for pressure-overload growth of the heart. Eventually, these data suggest that histone acetylation may be a novel target for therapeutic intervention in pressure-overloaded cardiac hypertrophy.

• 대한수의학회지
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• 제45권4호
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• pp.537-544
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• 2005

We have examined distribution and expression of caveolin-3 (cav-3), one of three caveolin isoforms from 16-wks-old spontaneously hypertensive rats (SHR) compared with age-matched control wistar-kyoto (WKY) rats. The expression of cav-3 was increased, whereas expression of PKB/Akt and calcineurin (Cn) was not changed in cardiac tissues of SHR compared to WKY rats. Interestingly, expression of cav-3, PKB/Akt and Cn were decreased in plasma membrane fraction in SHR compared to WKY rats. In H9c2 cardiomyoblast cells treated with phenylephrine ($50{\mu}M$, 48hr) or isoproterenol ($10{\mu}M$, 48hr), the expression of cav-3 was markedly enhanced compared to nontreated cells. Upon immunofluorescence analysis, cav-3 was localized in plasma membrane of control H9c2 cells. However phenylephrine or isoproterenol treatment caused translocation of cav-3 to perinuclear region. These results suggest that cav-3 plays as positive regulators in the development of hypertrophy in cardiac tissues of SHR rats.

• 동의생리병리학회지
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• 제17권2호
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• pp.363-367
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• 2003

Oriental pear was used as treatment of asthma, control of blood pressure tonic medicine vasoaction, diabetes in oriental medicine. In this study, it was investigated that pear phenolic compound effects on cardiovascular system as blood pressure and renin and atrial natriuretic peptide(ANP) in plasma, Cardiac hypertrophy. The experiments were performed on Sprague Dawley rats, 2K1C hypertension model was prepared by constricting the left renal artery with a sliver clip. Animals were then divided into four groups, 5mg/Kg(PPC-A) 10mg/Kg(PPC-B) 15mg/Kg(PPC-c) and control group. Pear phenolic compound solution were supplied with them for 3weeks, a day's interval. The results are that The blood pressure was significantly decreased at 15days in PPC-A group than control group. The plasma ANP was increased in PPC-A and PPC-C group, and cardiac hypertrophy was significantly decrease in PPC-C group compared with control group.