Excess of glucocorticoid induces myocardial remodeling and alteration of calcium signaling in cardiomyocytes

Ventricular dysfunction is one of the important side effects of the anti-inflammatory agent, glucocorticoid (GC). The present study was undertaken to examine whether abnormal calcium signaling is responsible for cardiac dysfunction due to an excess of GC hormone. The synthetic GC drug, dexamethasone (DEX), significantly (P<0.001, n=20) increased heart weight to body weight ratio, left ventricular remodeling, and fibrosis. The microarray analysis showed altered expression of several genes encoding calcium cycling/ion channel proteins in DEX-treated rat heart. The altered expression of some of the genes was validated by real-time PCR and western blotting analyses. The expression of the L-type calcium channels and calsequestrin was increased, whereas sarcoendoplasmic reticulum calcium transport ATPase 2a (SERCA2a) and junctin mRNAs were significantly reduced in DEX-treated rat left ventricular tissues. In neonatal rat ventricular cardiomyocytes, DEX also increased the level of mRNAs of atrial- and brain natriuretic peptides, L-type calcium channels, and calsequestrin after 24 h of treatment, which were mostly restored by mifepristone. The caffeine-induced calcium release was prolonged by DEX compared to the sharp release in control cardiomyocytes. Taken together, these data show that impaired calcium kinetics may be responsible for cardiac malfunction by DEX. The results are important in understanding the pathophysiology of the heart in patients treated with excess GC.

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Resveratrol attenuates left ventricular remodeling in old rats with COPD induced by cigarette smoke exposure and LPS instillation

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2012-0464 ◽

2013 ◽

Vol 91 (12) ◽

pp. 1044-1054 ◽

Cited By ~ 14

Author(s):

Yi Xin Hu ◽

Hua Cui ◽

Li Fan ◽

Xiu Jie Pan ◽

Ji Hua Wu ◽

...

Keyword(s):

Ventricular Remodeling ◽

Left Ventricular Remodeling ◽

Quantitative Polymerase Chain Reaction ◽

Weight Ratio ◽

Left Ventricular ◽

Therapeutic Modality ◽

Heart Weight ◽

Cigarette Smoke Exposure ◽

Chronic Obstructive ◽

Old Rats

The objective of this study was to investigate left cardiac damage and the cardioprotective effects of resveratrol in old rats with COPD. Rats 22 months old were divided into three groups: control (CTL), smoking and lipopolysaccharides (SM/LPS), and SM/LPS plus resveratrol (SM/LPS-Res). Cardiac function, pathology, oxidative stress, and apoptosis index were measured. Expression of myocardial SIRT1 was studied by real-time quantitative polymerase chain reaction (PCR) and Western blot detection. The heart weight – body weight ratio (LVW/BW) increased in the SM/LPS group compared with the CTL group. Both the LVW/BW and the area of fibrosis in the SM/LPS-Res group decreased compared with those in the SM/LPS group. 8-OHdG expression increased in cardiac tissue of rats in the SM/LPS group, which could be inhibited by resveratrol. Resveratrol significantly increased the activity of superoxide dismutase (SOD) and reduced the cardiac malonyldialdehyde (MDA) level in the SM/LPS-Res group. There was a significant decrease in the extent of cardiomyocyte apoptosis in the SM/LPS-Res group compared with the SM/LPS group. SIRT1 mRNA increased in the SM/LPS-Res group compared with the SM/LPS group. In conclusion, resveratrol attenuated cardiac oxidative damage and left ventricular remodeling and enhanced the decreased expression of SIRT1 in hearts of old rats with emphysema and thus might be a therapeutic modality for cardiac injury complicated in chronic obstructive pulmonary disease (COPD).

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Hyperoxia-induced hypertrophy and ion channel remodeling in left ventricle

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00474.2012 ◽

2013 ◽

Vol 304 (12) ◽

pp. H1651-H1661 ◽

Cited By ~ 14

Author(s):

Siva K. Panguluri ◽

Jared Tur ◽

Jutaro Fukumoto ◽

Wei Deng ◽

Kevin B. Sneed ◽

...

Keyword(s):

Ventricular Remodeling ◽

Left Ventricular Remodeling ◽

Left Ventricular ◽

Heart Weight ◽

Cardiac Complications ◽

Cross Sectional ◽

Junction Protein ◽

Mrna And Protein Expression ◽

Microrna Processing ◽

And Control

Ventricular arrhythmias account for high mortality in cardiopulmonary patients in intensive care units. Cardiovascular alterations and molecular-level changes in response to the commonly used oxygen treatment remains unknown. In the present study we investigated cardiac hypertrophy and cardiac complications in mice subjected to hyperoxia. Results demonstrate that there is a significant increase in average heart weight to tibia length (22%) in mice subjected to hyperoxia treatment vs. normoxia. Functional assessment was performed in mice subjected to hyperoxic treatment, and results demonstrate impaired cardiac function with decreased cardiac output and heart rate. Staining of transverse cardiac sections clearly demonstrates an increase in the cross-sectional area from hyperoxic hearts compared with control hearts. Quantitative real-time RT-PCR and Western blot analysis indicated differential mRNA and protein expression levels between hyperoxia-treated and control left ventricles for ion channels including Kv4.2 (−2 ± 0.08), Kv2.1 (2.54 ± 0.48), and Scn5a (1.4 ± 0.07); chaperone KChIP2 (−1.7 ± 0.06); transcriptional factors such as GATA4 (−1.5 ± 0.05), Irx5 (5.6 ± 1.74), NFκB1 (4.17 ± 0.43); hypertrophy markers including MHC-6 (2.17 ± 0.36) and MHC-7 (4.62 ± 0.76); gap junction protein Gja1 (4.4 ± 0.8); and microRNA processing enzyme Drosha (4.6 ± 0.58). Taken together, the data presented here clearly indicate that hyperoxia induces left ventricular remodeling and hypertrophy and alters the expression of Kv4.2 and MHC6/7 in the heart.

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Lansoprazole alleviates pressure overload-induced cardiac hypertrophy and heart failure in mice by blocking the activation of β-catenin

Cardiovascular Research ◽

10.1093/cvr/cvz016 ◽

2019 ◽

Vol 116 (1) ◽

pp. 101-113 ◽

Cited By ~ 4

Author(s):

Hairuo Lin ◽

Yang Li ◽

Hailin Zhu ◽

Qiancheng Wang ◽

Zhenhuan Chen ◽

...

Keyword(s):

Heart Failure ◽

Body Weight ◽

Angiotensin Ii ◽

Cardiac Hypertrophy ◽

Weight Ratio ◽

Left Ventricular ◽

Neonatal Rat ◽

Cardiac Remodelling ◽

Heart Weight ◽

Body Weight Ratio

Abstract Aims Proton pump inhibitors (PPIs) are widely used in patients receiving percutaneous coronary intervention to prevent gastric bleeding, but whether PPIs are beneficial for the heart is controversial. Here, we investigated the effects of lansoprazole on cardiac hypertrophy and heart failure, as well as the underlying mechanisms. Methods and results Adult male C57 mice were subjected to transverse aortic constriction (TAC) or sham surgery and then were treated with lansoprazole or vehicle for 5 weeks. In addition, cultured neonatal rat ventricular cardiomyocytes and fibroblasts were exposed to angiotensin II in the presence or absence of lansoprazole. At 5 weeks after TAC, the heart weight/body weight ratio was lower in lansoprazole-treated mice than in untreated mice, as was the lung weight/body weight ratio, while left ventricular (LV) fractional shortening and the maximum and minimum rates of change of the LV pressure were higher in lansoprazole-treated mice, along with less cardiac fibrosis. In cultured cardiomyocytes, lansoprazole inhibited angiotensin II-induced protein synthesis and hypertrophy, as well as inhibiting proliferation of fibroblasts. Lansoprazole decreased myocardial levels of phosphorylated Akt, phosphorylated glycogen synthase kinase 3β, and active β-catenin in TAC mice and in angiotensin II-stimulated cardiomyocytes. After overexpression of active β-catenin or knockdown of H+/K+-ATPase α-subunit, lansoprazole still significantly attenuated myocyte hypertrophy. Conclusion Lansoprazole inhibits cardiac remodelling by suppressing activation of the Akt/GSK3β/β-catenin pathway independent of H+/K+-ATPase inhibition, and these findings may provide a novel insight into the pharmacological effects of PPIs with regard to alleviation of cardiac remodelling.

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Left ventricular remodeling with exercise in hypertension

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01253.2008 ◽

2009 ◽

Vol 297 (4) ◽

pp. H1361-H1368 ◽

Cited By ~ 28

Author(s):

Stephen C. Kolwicz ◽

Scott M. MacDonnell ◽

Brian F. Renna ◽

Patricia O. Reger ◽

Rachid Seqqat ◽

...

Keyword(s):

Exercise Training ◽

Progenitor Cells ◽

Ventricular Remodeling ◽

Left Ventricular Remodeling ◽

Left Ventricular ◽

Treadmill Running ◽

Heart Weight ◽

Cardiomyocyte Hypertrophy ◽

Chronic Hypertension ◽

Cardiac Progenitor Cells

We investigated how exercise training superimposed on chronic hypertension impacted left ventricular remodeling. Cardiomyocyte hypertrophy, apoptosis, and proliferation in hearts from female spontaneously hypertensive rats (SHRs) were examined. Four-month-old SHR animals were placed into a sedentary group (SHR-SED; n = 18) or a treadmill running group (SHR-TRD, 20 m/min, 1 h/day, 5 days/wk, 12 wk; n = 18). Age-matched, sedentary Wistar Kyoto (WKY) rats were controls ( n = 18). Heart weight was greater in SHR-TRD vs. both WKY ( P < 0.01) and SHR-SED ( P < 0.05). Morphometric-derived left ventricular anterior, posterior, and septal wall thickness were increased in SHR-SED relative to WKY and augmented in SHR-TRD. Cardiomyocyte surface area, length, and width were increased in SHR-SED relative to WKY and further increased in SHR-TRD. Calcineurin abundance was increased in SHR-SED vs. WKY ( P < 0.001) and attenuated in SHR-TRD relative to SHR-SED ( P < 0.05). Protein abundance and mRNA of Akt was not different among groups. The rate of apoptosis was increased in SHR-SED relative to WKY and mitigated in SHR-TRD. The abundance of Ki-67+ cells across groups was not statistically different across groups. The abundance of cardiac progenitor cells (c-Kit+ cells) was increased in SHR-TRD relative to WKY. These data suggest that exercise training superimposed on hypertension augmented cardiomyocyte hypertrophy, despite attenuating calcineurin abundance. Exercise training also mitigated apoptosis in hypertension and showed a tendency to enhance the abundance of cardiac progenitor cells, resulting in a more favorable cardiomyocyte number in the exercise-trained hypertensive heart.

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WAS THE CLASSIFICATION ABLE TO DIVIDE DOGS WITH MYXOMATOUS MITRAL VALVE DISEASE ACCORDING TO THE SEVERITY OF THE DISEASE?

BULGARIAN JOURNAL OF VETERINARY MEDICINE ◽

10.15547/tjs.2020.01.008 ◽

2020 ◽

Vol 23 (1) ◽

pp. 41-45

Author(s):

A. Pankov

Keyword(s):

Mitral Valve ◽

Pulmonary Edema ◽

Mitral Valve Disease ◽

Ventricular Remodeling ◽

Left Ventricular Remodeling ◽

Weight Ratio ◽

Left Ventricular ◽

Valve Disease ◽

Severity Of The Disease ◽

Chronic Course

Using the simultaneous readings of the left ventricular remodeling model and the left ventricular weight to body weight ratio, the Gaasch and Zile classification was able to distinguish almost completely (95%) the dogs without pulmonary edema from those with pulmonary edema in cases of MMVD (myxomatous mitral valve disease) with an established limit for the left ventricular mass of 7.478 g/kg between the two groups. In one of the twenty animals surveyed, the classification failed. We assume that this is related to the exacerbation of the disease and the change of its chronic course due to an additional cause.

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