Huoxue Wentong Formula ameliorates myocardial infarction in rats through inhibiting CaMKII oxidation and phosphorylation

Abstract Background The Chinese medicine Huoxue Wentong Formula (HXWTF) was used to treat thoracic obstruction and angina pectoris in clinic, which has not been investigated in myocardial ischemia-induced apoptosis and angiogenic function. Here we aimed to investigate the roles of HXWTF in rats with myocardial ischemia-induced apoptosis and angiogenesis disorders, as well as to reveal the potential mechanisms. Methods Male SD rats were subjected to coronary artery ligation followed by HXWTF (420, 840 and 1680 mg/kg/day, p.o.) or isosorbide mononitrate (6.3 mg/kg/day, p.o.) treatment for 4 weeks. Electrocardiogram (ECG) and Echocardiography (ECHO) were used to measure cardiac function. Hematoxylin and eosin (H&E) staining and CD34/α-SMA immunohistochemical staining were performed to observe the ischemic heart sections pathological changes and angiogenesis. Then, the effects on cardiomyocyte apoptosis of H9c2 and tube formation of HCMECs were observed, as well as the changes in the levels of total calmodulin dependent protein kinase II (t-CaMKII), phosphorylated CaMKII (p-CaMKII), oxidized CaMKII (ox-CaMKII), CD34, and Bcl-2/Bax ratio were detected. Results Rats with coronary artery ligation exhibited abnormal cardiac function, enlarged myocardial space, disorderly arranged myocardial fibers, inflammatory cells infiltrated, and aggravated myocardial cell apoptosis, along with angiogenesis dysfunction. The expressions of CD34, p-CaMKII, and ox-CaMKII were elevated and Bcl-2/Bax ratio was diminished in ischemic hearts and H/SD-treated H9c2 or HCMECs, while HXWTF treatment completely rescued angiogenic dysfunction, inhibited cardiomyocyte apoptosis, and down-regulated cardiac CaMKII oxidation and phosphorylation activities. Conclusion Our study demonstrates that HXWTF improves myocardial infarction possibly through inhibiting CaMKII oxidation and phosphorylation levels, facilitating angiogenic function and alleviating cardiomyocyte apoptosis. Thus, therapeutics targeting CaMKII activities may be a promising strategy for rescuing ischemic cardiomyopathy.

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iASPP protects the heart from ischemia injury by inhibiting p53 expression and cardiomyocyte apoptosis

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmaa104 ◽

2020 ◽

Author(s):

Timur Yagudin ◽

Yue Zhao ◽

Haiyu Gao ◽

Yang Zhang ◽

Ying Yang ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Cardiac Function ◽

Infarct Size ◽

Cardiomyocyte Apoptosis ◽

Coronary Artery Ligation ◽

Novel Therapy ◽

Artery Ligation ◽

P53 Expression

Abstract Currently, there remains a great need to elucidate the molecular mechanism of acute myocardial infarction in order to facilitate the development of novel therapy. Inhibitor of apoptosis-stimulating protein of p53 (iASPP) is a member of the ASPP family proteins and an evolutionarily preserved inhibitor of p53 that is involved in many cellular processes, including apoptosis of cancer cells. The purpose of this study was to investigate the possible role of iASPP in acute myocardial infarction. The protein level of iASPP was markedly reduced in the ischemic hearts in vivo and hydrogen peroxide-exposed cardiomyocytes in vitro. Overexpression of iASPP reduced the infarct size and cardiomyocyte apoptosis of mice subjected to 24 h of coronary artery ligation. Echocardiography showed that cardiac function was improved as indicated by the increase in ejection fraction and fractional shortening. In contrast, knockdown of iASPP exacerbated cardiac injury as manifested by impaired cardiac function, increased infarct size, and apoptosis rate. Mechanistically, overexpression of iASPP inhibited, while knockdown of iASPP increased the expressions of p53 and Bax, the key regulators of apoptosis. Taken together, our results suggested that iASPP is an important regulator of cardiomyocyte apoptosis, which represents a potential target in the therapy of myocardial infarction.

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Cardiac protection of germinated brown rice extract in rabbit model of chronic myocardial infarction

Translational Animal Science ◽

10.1093/tas/txaa067 ◽

2020 ◽

Vol 4 (2) ◽

pp. 1031-1037

Author(s):

Soontaree Petchdee ◽

Wanpen Laosripaiboon ◽

Nongpanga Jarussophon

Keyword(s):

Myocardial Infarction ◽

Coronary Artery ◽

Myocardial Ischemia ◽

Rabbit Model ◽

Brown Rice ◽

Coronary Artery Ligation ◽

Chronic Myocardial Infarction ◽

Artery Ligation ◽

Germinated Brown Rice ◽

Cardioprotective Effects

Abstract Ischemic heart disease is a leading cause of mortality in the world. This study aimed to investigate the cardioprotective effects of germinated brown rice (GBR) on a rabbit model of chronic myocardial infarction. Eighteen New Zealand white rabbits were randomly divided into three groups receiving: 1) regular rabbit food; 2) regular rabbit food plus vehicle; and 3) regular rabbit food plus GBR for 120 d. The left circumflex coronary artery was ligated to induce myocardial ischemia 60 d after starting the experiment (baseline). Heart functions were monitored by electrocardiography and echocardiography at 0, 30, and 60 d after coronary artery ligation. The incidences of heart rate (HR) and ventricular arrhythmias have been compared between groups. GBR showed the effects to prevent life-threatening ventricular tachycardia and electrocardiographic signs of myocardial ischemia in a model of arrhythmias. GBR consumption group exhibited significantly improved cardiac function and reduced the HR, along with reduced mean arterial pressure and plasma glucose level. The results demonstrated that GBR exerts cardioprotective effects against chronic myocardial injury in rabbits. These biological actions of GBR may explain the benefits gained from the use of GBR products as a possible prophylactic lifestyle intervention.

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Endothelial β1 Integrin-Mediated Adaptation to Myocardial Ischemia

Thrombosis and Haemostasis ◽

10.1055/s-0040-1721505 ◽

2021 ◽

Author(s):

Carina Henning ◽

Anna Branopolski ◽

Paula Follert ◽

Oksana Lewandowska ◽

Aysel Ayhan ◽

...

Keyword(s):

Myocardial Infarction ◽

Coronary Artery ◽

Myocardial Ischemia ◽

Cardiac Function ◽

Integrin Subunit ◽

Β1 Integrin ◽

Human Coronary Artery ◽

Tetrazolium Chloride ◽

Magnetic Resonance Imaging Mri ◽

Interfering Rna

Abstract Background Short episodes of myocardial ischemia can protect from myocardial infarction. However, the role of endothelial β1 integrin in these cardioprotective ischemic events is largely unknown. Objective In this study we investigated whether endothelial β1 integrin is required for cardiac adaptation to ischemia and protection from myocardial infarction. Methods Here we introduced transient and permanent left anterior descending artery (LAD) occlusions in mice. We inhibited β1 integrin by intravenous injection of function-blocking antibodies and tamoxifen-induced endothelial cell (EC)-specific deletion of Itgb1. Furthermore, human ITGB1 was silenced in primary human coronary artery ECs using small interfering RNA. We analyzed the numbers of proliferating ECs and arterioles by immunohistochemistry, determined infarct size by magnetic resonance imaging (MRI) and triphenyl tetrazolium chloride staining, and analyzed cardiac function by MRI and echocardiography. Results Transient LAD occlusions were found to increase EC proliferation and arteriole formation in the entire myocardium. These effects required β1 integrin on ECs, except for arteriole formation in the ischemic part of the myocardium. Furthermore, this integrin subunit was also relevant for basal and mechanically induced proliferation of human coronary artery ECs. Notably, β1 integrin was needed for cardioprotection induced by transient LAD occlusions, and the absence of endothelial β1 integrin resulted in impaired growth of blood vessels into the infarcted myocardium and reduced cardiac function after permanent LAD occlusion. Conclusion We showed that endothelial β1 integrin is required for adaptation of the heart to cardiac ischemia and protection from myocardial infarction.

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Comparison of Myocardial Infarction with Sequential Ligation of the Left Anterior Descending Artery and Its Diagonal Branch in Dogs and Sheep

The International Journal of Artificial Organs ◽

10.1177/039139880302600411 ◽

2003 ◽

Vol 26 (4) ◽

pp. 351-357 ◽

Cited By ~ 10

Author(s):

W.G. Kim ◽

Y.C. Shin ◽

S.W. Hwang ◽

C. Lee ◽

C.Y. Na

Keyword(s):

Myocardial Infarction ◽

Coronary Artery ◽

Pulmonary Artery ◽

Left Ventricular ◽

Coronary Artery Ligation ◽

Suitable Model ◽

Artery Ligation ◽

Diagonal Branch ◽

Left Anterior Descending Artery ◽

Arterial Blood

We report a comparison of the effects of myocardial infarction in dogs and sheep using sequential ligation of the left anterior descending artery (LAD) and its diagonal branch (DA), with hemodynamic, ultrasonographic and pathological evaluations. Five animals were used in each group. After surgical preparation, the LAD was ligated at a point approximately 40% of the distance from the apex to the base of the heart, and after one hour, the DA was ligated at the same level. Hemodynamic and ultrasonographic measurements were performed preligation, 30 minutes after LAD ligation, and 1 hour after DA ligation. As a control, two animals in each group were used for the simultaneous ligation of the LAD and the DA. Two months after the coronary ligation, the animals were evaluated as previously, and killed for postmortem examination of their hearts. All seven animals in the dog group survived the experimental procedures, while in the sheep group only animals with sequential ligation of the LAD and DA survived. Statistically significant decreases in systemic arterial blood pressure and cardiac output, and an increase in the pulmonary artery capillary wedge pressure (PACWP) were observed one hour after sequential ligation of the LAD and its DA in the sheep, while only systemic arterial pressures decreased in the dog. Ultrasonographic analyses demonstrated variable degrees of anteroseptal dyskinesia and akinesia in all sheep, but in no dogs. Data two months after coronary artery ligation showed significant increases in central venous pressure, pulmonary artery pressure, and PACWP in the sheep, but not in the dog. Left ventricular end-diastolic dimension and left ventricular end-systolic dimension in ultrasonographic studies were also increased only in the sheep. Pathologically, the well-demarcated thin-walled transmural anteroseptal infarcts with chamber enlargement were clearly seen in all specimens of sheep, and only-mild-to-moderate chamber enlargements with endocardial fibrosis were observed in the dog hearts. In conclusion, this study confirms that the dog is not a suitable model for myocardial infarction with failure by coronary artery ligation despite negligent operative mortality, when compared directly with an ovine model.

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A new technique of coronary artery ligation: Experimental myocardial infarction in rats in vivo with reduced mortality

The Cellular Basis of Cardiovascular Function in Health and Disease ◽

10.1007/978-1-4615-5765-4_29 ◽

1997 ◽

pp. 227-233

Author(s):

Jian Ye ◽

Luojia Yang ◽

Rajat Sethi ◽

John Copps ◽

Bram Ramjiawan ◽

...

Keyword(s):

Myocardial Infarction ◽

Coronary Artery ◽

Experimental Myocardial Infarction ◽

New Technique ◽

Coronary Artery Ligation ◽

Artery Ligation ◽

A New Technique

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Circulating Long Noncoding RNA HOTAIR is an Essential Mediator of Acute Myocardial Infarction

Cellular Physiology and Biochemistry ◽

10.1159/000485588 ◽

2017 ◽

Vol 44 (4) ◽

pp. 1497-1508 ◽

Cited By ~ 29

Author(s):

Lu Gao ◽

Yuan Liu ◽

Sen Guo ◽

Rui Yao ◽

Leiming Wu ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Coronary Artery ◽

Neonatal Rat ◽

Luciferase Reporter ◽

Coronary Artery Ligation ◽

Healthy Controls ◽

Artery Ligation ◽

Cultured Cardiomyocytes

Background/Aims: Acute myocardial infarction (AMI) is one of the leading causes of death in the world. However, specific diagnostic biomarkers have not been fully determined, and candidate regulatory targets for AMI have not been identified to date. Long noncoding RNAs (lncRNAs) are a class of RNA molecules that have diverse regulatory functions during embryonic development, normal life, and disease in higher organisms. However, research on the role of lncRNAs in cardiovascular diseases, particularly AMI, is still in its infancy. HOX antisense intergenic RNA (HOTAIR), a 2.2 kb lncRNA, was initially described as a modulator of HOX gene expression. Recent studies have illustrated the important role of HOTAIR in cancer progression, but few studies have reported its function in cardiac disease, including AMI. In the current study, we aimed to detect the expression of HOTAIR during AMI and to explore its function in hypoxia-induced cardiomyocyte injury in neonatal cardiomyocytes. Methods: In 50 consecutively enrolled AMI patients, we examined the serum expression levels of HOTAIR and analysed its correlation with cardiac troponin I (cTnI) expression. Another 50 age- and sex-matched subjects served as healthy controls. Next, the HOTAIR expression was detected in the serum from C57BL/6J mice subjected to coronary artery ligation and in neonatal rat cardiomyocytes induced by hypoxia. Cultured cardiomyocytes apoptosis were measured by terminal deoxynucleotide transferase dUTP nick end labelling (TUNEL) staining. A search for miRNAs that had complementary base paring with HOTAIR was performed utilizing an online software program, and the interaction between miR-1 and HOTAIR was examined using a luciferase reporter assay. Results: Our study revealed that HOTAIR expression was significantly decreased in the serum of AMI patients compared with that of the healthy controls. Similarly, we observed that HOTAIR was downregulated in the serum of mice subjected to coronary artery ligation and in cultured cardiomyocytes exposed to hypoxia. Furthermore, we observed that the adenovirus vector-driven overexpression of HOTAIR dramatically limited hypoxia-induced myocyte apoptosis, whereas knockdown HOTAIR by AdshHOTAIR (adenoviral short hairpin HOTAIR) exhibited the opposite phenotype. Mechanistically, we discovered that the cardioprotective function of HOTAIR is partly based on the negative regulation of miR-1. Conclusions: Taken together, the results of our study suggest that HOTAIR is a protective factor for cardiomyocytes and that the plasma concentration of HOTAIR may serve as a biomarker for human AMI diagnosis.

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Effects of carbon nanotube-mediated Caspase3 gene silencing on cardiomyocyte apoptosis and cardiac function during early acute myocardial infarction

Nanoscale ◽

10.1039/d0nr05032f ◽

2020 ◽

Vol 12 (42) ◽

pp. 21599-21604

Author(s):

Yi Li ◽

Hong Yu ◽

Liang Zhao ◽

Yuting Zhu ◽

Rui Bai ◽

...

Keyword(s):

Myocardial Infarction ◽

Cardiac Function ◽

Gene Silencing ◽

Ventricular Remodeling ◽

Myocardial Cell ◽

Coronary Artery Ligation ◽

Protective Effects ◽

Sprague Dawley ◽

Artery Ligation ◽

Sd Rats

Caspase3 gene silencing based on the gene transfer carrier F-CNT-siCas3 had obvious protective effects on myocardial cell apoptosis, ventricular remodeling, and cardiac function in Sprague-Dawley (SD) rats after coronary artery ligation.

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