Effect of metoprolol on myocardial apoptosis after coronary microembolization in rats

Su, Qiang; Li, Lang; Liu, Yangchun; Zhou, You; Wen, Wang

doi:10.5847/wjem.j.issn.1920-8642.2013.02.010

Cited by 15 publications

(21 citation statements)

References 22 publications

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“…All β-blockers are known to inhibit cardiomyocyte apoptosis [ 7 – 10 ]. However, changes in CI over time in response to treatment with different β-blockers were not similar.…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies have shown that β-blockers are effective in mitigating cardiomyocyte apoptosis and they are the standard of care to reduce infarct size after cardiac ischemia. Aten and Met are 2 nd generation cardioselective β-blockers that reduce cardiomyocyte apoptosis caused by conditions such as coronary microembolization and exposure to lipopolysaccharides (LPS) [ 7 , 8 ]. Car and Neb are 3 rd generation β-blockers with additional vasodilative effects [ 9 , 10 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

“…Cardiomyocyte death via necrosis, apoptosis and impaired autophagy are hallmarks of cardiac pathology associated with heart failure, myocardial infarction and ischemia/reperfusion injury [ 3 – 6 ]. Anti-hypertensive drugs such as β-adrenergic receptor blockers (β-blockers) and inhibitors of angiotensin II type 1 receptor (AT1R) are reported to exert cardioprotective effects by reducing cardiomyocyte death [ 7 – 11 ].…”

Section: Introductionmentioning

confidence: 99%

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Differential Effects of β-Blockers, Angiotensin II Receptor Blockers, and a Novel AT2R Agonist NP-6A4 on Stress Response of Nutrient-Starved Cardiovascular Cells

Mahmood

Pulakat

2015

PLoS ONE

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In order to determine differences in cardiovascular cell response during nutrient stress to different cardiovascular protective drugs, we investigated cell responses of serum starved mouse cardiomyocyte HL-1 cells and primary cultures of human coronary artery vascular smooth muscles (hCAVSMCs) to treatment with β-blockers (atenolol, metoprolol, carvedilol, nebivolol, 3μM each), AT1R blocker losartan (1μM) and AT2R agonists (CGP42112A and novel agonist NP-6A4, 300nM each). Treatment with nebivolol, carvedilol, metoprolol and atenolol suppressed Cell Index (CI) of serum-starved HL-1 cells (≤17%, ≤8%, ≤15% and ≤15% respectively) as measured by the Xcelligence Real-Time Cell Analyzer (RTCA). Conversely, CI was increased by Ang II (≥9.6%), CGP42112A (≥14%), and NP-6A4 (≥25%) respectively and this effect was blocked by AT2R antagonist PD123319, but not by AT1R antagonist losartan. Thus, the CI signature for each drug could be unique. MTS cell proliferation assay showed that NP-6A4, but not other drugs, increased viability (≥20%) of HL-1 and hCAVSMCs. Wheat Germ Agglutinin (WGA) staining showed that nebivolol was most effective in reducing cell sizes of HL-1 and hCAVSMCs. Myeloid Cell Leukemia 1 (MCL-1) is a protein critical for cardiovascular cell survival and implicated in cell adhesion. β-blockers significantly suppressed and NP-6A4 increased MCL-1 expression in HL-1 and hCAVSMCs as determined by immunofluorescence. Thus, reduction in cell size and/or MCL-1 expression might underlie β-blocker-induced reduction in CI of HL-1. Conversely, increase in cell viability and MCL-1 expression by NP-6A4 through AT2R could have resulted in NP-6A4 mediated increase in CI of HL-1. These data show for the first time that activation of the AT2R-MCL-1 axis by NP-6A4 in nutrient-stressed mouse and human cardiovascular cells (mouse HL-1 cells and primary cultures of hCAVSMCs) might underlie improved survival of cells treated by NP-6A4 compared to other drugs tested in this study.

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“…All β-blockers are known to inhibit cardiomyocyte apoptosis [ 7 – 10 ]. However, changes in CI over time in response to treatment with different β-blockers were not similar.…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Differential Effects of β-Blockers, Angiotensin II Receptor Blockers, and a Novel AT2R Agonist NP-6A4 on Stress Response of Nutrient-Starved Cardiovascular Cells

Mahmood

Pulakat

2015

PLoS ONE

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“…Five fields were randomly selected in each HBFP staining (×100), and infarction area was quantified by 2D deconvolution algorithm using the Leica QWin imaging software (Leica Company) and demonstrated as the average percentage of the total area of the section analyzed. 24 The relative ischemic area was calculated as follows: ischemic area/total area × 100%.…”

Section: Tissue Collection and Sample Processingmentioning

confidence: 99%

Ultrasound-targeted microbubble destruction-mediated microRNA-21 transfection regulated PDCD4/NF-κB/TNF-α pathway to prevent coronary microembolization-induced cardiac dysfunction

Liu

et al. 2015

Gene Ther

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The programmed cell death 4/nuclear factor-κB/tumor necrosis factor α (PDCD4/NF-κB/TNF-α) signaling pathway has an important role in coronary microembolization (CME)-induced inflammation. microRNA-21 protects myocardium mainly via regulation of its target gene PDCD4. Therefore, in this study we investigated the effect of ultrasound-guided microbubble-mediated microRNA-21 transfection on cardiac function in CME pig model and determined the potential mechanisms involved. The pig CME model was established by microcatheter-mediated injection of microembolization beads into the left anterior descending artery. The CME with microRNA transfection group was injected with plasmid-microbubble mixture through the marginal ear vein 4 days before CME treatment, along with ultrasound to the myocardium. Cardiac function indices were examined by cardiac ultrasound; infarct area was measured by hematoxylin-eosin and hematoxylin-basic Fuchsin-picric acid staining of tissue pathological sections; green fluorescent protein-labeled gene expression levels were evaluated by fluorescent microscopy in frozen sections; myocardial PDCD4 and TNF-α mRNA levels were measured by fluorescent quantitative PCR and protein levels were measured by western blotting; and NF-κB activity was tested by electrophoretic mobility shift assay. Compared with the CME group, the CME with ultrasound-mediated microRNA transfection group demonstrated improved CME-induced cardiac dysfunction (P<0.05). Compared with the CME group, the CME with ultrasound-mediated microRNA transfection group showed significantly lower PDCD4 expression and NF-κB activity (P<0.05). Ultrasound microbubble-mediated microRNA-21 transfection effectively improved CME-induced cardiac dysfunction via inhibition of PDCD4/NF-κB/TNF-α signal transduction pathway.

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“…All three measurements represented the averages of three cardiac cycles. 10 Echocardiographic examination was performed by an experienced echocardiography specialist.…”

Section: Cardiac Function Evaluationmentioning

confidence: 99%

Mechanism of programmed cell death factor 4/nuclear factor-κB signaling pathway in porcine coronary micro-embolization-induced cardiac dysfunction

Wang

et al. 2015

Exp Biol Med (Maywood)

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The aim of this study was to investigate the role of the programmed cell death factor 4 (PDCD4)/nuclear factor-kB (NF-kB) signaling pathway in coronary micro-embolism (CME)-induced inflammatory responses and cardiac dysfunction in a porcine model. Bama miniature pigs were randomly divided into four groups (n ¼ 5 per group). Micro-embolization balls or saline were infused through a microcatheter in the left anterior descending (LAD) artery in the CME and Sham groups, respectively. PDCD4 siRNA or control siRNA mixed with transfection reagent was infused via the LAD artery 72 h before CME induction in the CME þ siRNA-PDCD4 and siRNA-control groups, respectively. Cardiac function was evaluated with ultrasound. Tissue biopsy was stained with hematoxylin-eosin (HE) and hematoxylin basic fuchsin picric acid (HBFP) to measure infarction area. Myocardial PDCD4 and tumor necrosis factor-a (TNF-a) mRNA and protein expression were analyzed by quantitative PCR and Western blotting. NF-kB activity was evaluated in gel electrophoretic mobility shift assay. Echocardiographic parameters showed that compared with the sham group, the CME group had impaired heart function, manifested as systolic dysfunction and left ventricular dilatation (reduced left ventricular ejection fraction [LVEF], left ventricular fractional shortening [FS], and cardiac output [CO] [P < 0.05] and increased left ventricular end-diastolic diameter [LVEDd] [P < 0.05]). Compared with the CME group, the CME þ siRNA-PDCD4 group had attenuated CME-induced cardiac function damage (increased LVEF, FS and CO [P < 0.05] and reduced LVEDd [P < 0.05]). Compared with the sham group, the CME group had significantly increased PDCD4 and TNF-a mRNA and protein expression and increased NF-kB activity (P < 0.05). These effects were significantly inhibited in the CME þ siRNA-PDCD4 group (P < 0.05). In conclusion, PDCD4/NF-kB signaling pathway activation is an important mechanism for CME-induced cardiac dysfunction, suggesting that inhibition of PDCD4/NF-kB signaling pathway may be a potential target for the prevention and treatment of CME.

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Effect of metoprolol on myocardial apoptosis after coronary microembolization in rats

Cited by 15 publications

References 22 publications

Differential Effects of β-Blockers, Angiotensin II Receptor Blockers, and a Novel AT2R Agonist NP-6A4 on Stress Response of Nutrient-Starved Cardiovascular Cells

Differential Effects of β-Blockers, Angiotensin II Receptor Blockers, and a Novel AT2R Agonist NP-6A4 on Stress Response of Nutrient-Starved Cardiovascular Cells

Ultrasound-targeted microbubble destruction-mediated microRNA-21 transfection regulated PDCD4/NF-κB/TNF-α pathway to prevent coronary microembolization-induced cardiac dysfunction

Mechanism of programmed cell death factor 4/nuclear factor-κB signaling pathway in porcine coronary micro-embolization-induced cardiac dysfunction

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