Licorice treatment prevents oxidative stress, restores cardiac function, and salvages myocardium in rat model of myocardial injury

Abstract Objective: A large cohort of studies have addressed the therapeutic importance of microRNA (miR) in the treatment of myocardial infarction (MI). The current paper gives prominence to the role of miR-322-5p in MI by regulating B-cell translocation gene 2 (BTG2).Methods: In a rat model of MI miR-322-5p and BTG2 expression was estimated. Adenovirus that altered miR-322-5p or BTG2 expression was injected into MI rats. After that, cardiac function, inflammation, myocardial injury, pathological condition, apoptosis, and the NF-κB pathway-related genes in the myocardial tissue of MI rats after targeted treatment were evaluated. The targeting relationship between miR-322-5p and BTG2 was assessed.Results: miR-322-5p was lowly expressed and BTG2 was highly expressed in the myocardial tissue of MI rats. Restored miR-322-5p improved cardiac function, relived inflammation and myocardial injury, suppressed pathological condition and apoptosis and inactivated NF-κB pathway in MI rats. BTG2 expression was negatively mediated by miR-322-5p. Overexpressed BTG2 rescued miR-322-5p-induced cardioprotection on MI rats.Conclusion: It is evident that miR-322-5p protects against MI through suppressing BTG2 expression.

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Abstract 036: Mitoprotection Preserves the Cytoskeleton and Alleviates Myocardial Injury in Early Swine Metabolic Syndrome

Hypertension ◽

10.1161/hyp.68.suppl_1.036 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

Fang Yuan ◽

John R Woollard ◽

Kyra L Jordan ◽

Amir Lerman ◽

Lilach O Lerman ◽

...

Keyword(s):

Oxidative Stress ◽

Metabolic Syndrome ◽

Cardiac Function ◽

Myocardial Injury ◽

Therapeutic Potential ◽

Multidetector Ct ◽

Early Stage ◽

Cardiac Injury ◽

Cytoskeletal Proteins ◽

Mitochondrial Structure

Background: The mechanisms responsible for cardiac injury in the early stage of metabolic syndrome (MetS) remain unknown. Mitochondria are intimately associated with myofibrils, where the cytoskeleton functions as a linkage coordinator. We hypothesized that early MetS is characterized by cytoskeletal-mitochondrial disorganization, and that mitoprotection with mitochondria-targeted peptides (MTP) would preserve cytoskeletal-mitochondrial structure and attenuate myocardial injury in early swine MetS. Methods: Pigs were studied after 16wks of diet-induced MetS, MetS treated for the last 4wks with the MTP Elamipretide (0.1mg/kg SC q.d), and Lean controls (n=6 each). Cardiac function (multidetector CT) was assessed in-vivo, and mitochondrial structure (electron microscopy), the mitochondrial inner membrane phospholipid cardiolipin (mass spectrometry), cytoskeletal proteins, oxidative stress, and apoptosis ex-vivo. Results: MetS pigs developed hypertension and insulin resistance, yet cardiac function was preserved. MetS induced loss of desmin and tubulin that was paralleled by mitochondrial disorganization, decreased 18:2 cardiolipin, and increased oxidative stress and apoptosis. MTP slightly improved cardiolipin species profile, restored mitochondrial organization, and upregulated cytoskeletal proteins, attenuating apoptosis and oxidative stress. Conclusion: Early MetS leads to disorganization of the cardiomyocyte cytoskeletal- mitochondrial architecture and cardiac injury. MTP may provide a novel therapeutic potential for improving cardiac injury in early MetS, and potentially preventing future deterioration in cardiac function.

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Selective inhibition of p38α MAPK improves cardiac function and reduces myocardial apoptosis in rat model of myocardial injury

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00043.2006 ◽

2006 ◽

Vol 291 (4) ◽

pp. H1972-H1977 ◽

Cited By ~ 46

Author(s):

Zhihe Li ◽

Jing Ying Ma ◽

Irene Kerr ◽

Sarvajit Chakravarty ◽

Sundeep Dugar ◽

...

Keyword(s):

Cardiac Function ◽

P38 Mapk ◽

Rat Model ◽

Myocardial Injury ◽

Myocardial Damage ◽

Cardiomyocyte Apoptosis ◽

Ang Ii ◽

P38α Mapk ◽

Cardioprotective Effects ◽

Mapk Inhibitor

p38 MAPK is activated during heart diseases that might associate with myocardial damage and deterioration of cardiac function. In a rat model of myocardial injury, we have investigated cardioprotective effects of the inhibition of p38 MAPK using a novel, orally available p38α MAPK inhibitor. Rats were treated with Nω-nitro-l-arginine methyl ester (l-NAME, 40 mg·kg−1·day−1) in drinking water plus 1% salt for 14 days and ANG II (0.5 mg·kg−1·day−1) for 3 days. A selective p38α MAPK inhibitor, SD-282 (60 mg/kg), was administrated orally, twice a day for 4 days, starting 1 day before ANG II administration. The cardioprotective effects of p38α MAPK inhibition were evaluated by improvement of cardiac function, reduction of inflammatory cell infiltration, and cardiomyocyte apoptosis. SD-282 significantly improved cardiac function indicated by increasing stroke volume, cardiac output, ejection fraction, and stroke work and significantly decreasing arterial elastance. SD-282 also significantly reduced macrophage infiltration as judged by reduction of a specific marker, ED-1-positive staining cells ( P < 0.05) in the myocardium. Furthermore, cardiomyocyte apoptosis as indicated by caspase-3 immunohistochemical staining was abolished by SD-282, and this effect may contribute to the reduction of myocardial damage evaluated by imaging analysis ( P < 0.05 in both cases). Data suggest that p38α MAPK may play a critical role in the pathogenesis of cardiac dysfunction. Inhibition of p38α MAPK may be used as a novel cardioprotective strategy in attenuation of inflammatory response and deterioration of cardiac function that occurs in acute cardiovascular disease such as myocardial infarction.

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Potential Involvement of MiR-30e-3p in Myocardial Injury Induced by Coronary Microembolization via Autophagy Activation

Cellular Physiology and Biochemistry ◽

10.1159/000485905 ◽

2017 ◽

Vol 44 (5) ◽

pp. 1995-2004 ◽

Cited By ~ 13

Author(s):

Xian-tao Wang ◽

Xiao-dan Wu ◽

Yuan-xi Lu ◽

Yu-han Sun ◽

Han-hua Zhu ◽

...

Keyword(s):

Cardiac Function ◽

Rat Model ◽

Myocardial Injury ◽

Sham Group ◽

Troponin I ◽

Related Protein ◽

Tissue Samples ◽

Autophagic Vacuoles ◽

Coronary Microembolization ◽

Ctni Level

Background/Aims: Coronary microembolization (CME) can lead to no-reflow or slow reflow, which is one of the important reasons for loss of clinical benefit from myocardial reperfusion therapy. MicroRNAs and autophagy are heavily implicated in the occurrence and development of almost all cardiovascular diseases. Therefore, the present study was designed to investigate the role of miR-30e-3p and autophagy in CME-induced myocardial injury rat model. Methods: Sixty rats were randomly divided into six groups: sham, CME 1h,3h,6h,9h, and 12h (n = 10 per group). Our CME rat model was created by injecting polyethylene microspheres (42mm) into the left ventricle of the heart; the sham group was injected with same volume of normal saline. The cardiac function and serum cardiac troponin I (cTnI) level of each group was measured. HE staining and HBFP staining were used to evaluate the myocardial micro-infarction area of myocardium tissue samples. Then RT-qPCR and western blot were used to detect the expression of miR-30e-3p and, autophagy related protein LC3-II and p62, respectively. Transmission electron microscope (TEM) was used to identify autophagic vacuoles in tissue samples. Results: The cardiac function of the CME 6h,9h, and 12h groups were significantly decreased compared to the sham group (P < 0.05) and the cTnI level in each group were also significantly increased (P < 0.05). The expression of miR-30e-3p in the CME 6h, 9h and 12h group were decreased significantly compared with the sham group (P < 0.05). Meanwhile, the expression of autophagy related protein LC3-II decreased significantly and p62 increased significantly in the CME 9h and 12h group (P < 0.05). TEM images showed typical autophagic vacuoles for each of the CME groups. Conclusions: Myocardial miR-30e-3p is down regulated after CME and is accompanied by inhibited autophagy and decreased cardiac function. Therefore, miR-30e-3p may be involved in CME-induced cardiac dysfunction by regulating myocardial autophagy.

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