Transcriptome analysis of the ischemia-reperfused remodeling myocardium: temporal changes in inflammation and extracellular matrix

2006 ◽  
Vol 25 (3) ◽  
pp. 364-374 ◽  
Author(s):  
Sashwati Roy ◽  
Savita Khanna ◽  
Donald E. Kuhn ◽  
Cameron Rink ◽  
Willis T. Williams ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Extracellular Matrix ◽  
Candidate Genes ◽  
Dna Microarrays ◽  
Molecular Mechanisms ◽  
Acute Infarction ◽  
Genes Encoding ◽  
Apoptosis And Inflammation ◽  
Microarray Studies

cDNA microarray analysis was performed to screen 15,000 genes and expressed sequence tags (ESTs) to identify changes in the ischemia-reperfused (I-R) rat myocardial transcriptome in the early ( day 2) and late ( day 7) inflammatory phases of acute myocardial infarction. Lists of candidate genes that were affected by I-R transiently (2 or 7 days only) or on a more sustained basis (2 and 7 days) were derived. The candidate genes represented three major functional categories: extracellular matrix, apoptosis, and inflammation. To expand on the findings from microarray studies that dealt with the two above-mentioned time points, tissues collected from days 0, 0.25, 2, 3, 5, and 7 after reperfusion were examined. Acute myocardial infarction resulted in upregulation of IL-6 and IL-18. Genes encoding extracellular matrix proteins such as types I and III collagen were upregulated in day 2, and that response progressively grew stronger until day 7 after I-R. Comparable response kinetics was exhibited by the candidate genes of the apoptosis category. Caspases-2, -3, and -8 were induced in response to acute infarction. Compared with the myocardial tissue from the sham-operated rats, tissue collected from the infarct region stained heavily positive for the presence of active caspase-3. Laser microdissection and pressure catapulting technology was applied to harvest infarct and adjacent noninfarct control tissue from a microscopically defined region in the rat myocardium. Taken together, this work presents the first evidence gained from the use of DNA microarrays to understand the molecular mechanisms implicated in the early and late inflammatory phases of the I-R heart.

Abstract 12: EMMPRIN-Targeted Magnetic Nanoparticles for in vivo Visualization and Regression of Acute Myocardial Infarction in a Model of Acute Coronary Artery Occlusion

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Irene Cuadrado ◽  
Maria Jose Garcia Miguel ◽  
Irene Herruzo ◽  
Mari Carmen Turpin ◽  
Ana Martin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Extracellular Matrix ◽  
Coronary Artery ◽  
Left Ventricle ◽  
Infarct Size ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Gadolinium Enhancement

Extracellular matrix metalloproteinase inducer EMMPRIN, is highly expressed in patients with acute myocardial infarction (AMI), and induces activation of several matrix metalloproteinases (MMPs), including MMP-9 and MMP-13. To prevent Extracellular matrix degradation and cardiac cell death we targeted EMMPRIN with paramagnetic/fluorescent micellar nanoparticles with an EMMPRIN binding peptide AP9 conjugated (NAP9), or an AP9 scramble peptide as a negative control (NAPSC). NAP9 binds to endogenous EMMPRIN as detected by confocal microscopy of cardiac myocytes and macrophages incubated with NAP and NAPSC in vitro, and in vivo in mouse hearts subjected to left anterior descending coronary artery occlusion (IV injection 50mγ/Kg NAP9 or NAP9SC). Administration of NAP9 at the same time or 1 hour after AMI reduced infarct size over a 20% respect to untreated and NAPSC injected mice, recovered left ventricle ejection fraction (LVEF) similar to healthy controls, and reduced EMMPRIN downstream MMP9 expression. In magnetic resonance scans of mouse hearts 2 days after AMI and injected with NAP9, we detected a significant gadolinium enhancement in the left ventricle respect to non-injected mice and to mice injected with NAPSC. Late gadolinium enhancement assays exhibited NAP9-mediated left ventricle signal enhancement as early as 30 minutes after nanoprobe injection, in which a close correlation between the MRI signal enhancement and left ventricle infarct size was detected. Taken together, these results point EMMPRIN targeted nanoprobes as a new tool for the treatment of AMI.

scholarly journals An Exploratory Factor Analysis of Circulating Extracellular Matrix Biomarkers in Acute Myocardial Infarction

2019 ◽  
Vol 28 ◽  
pp. S14
Author(s):  
Morgane Brunton-O'Sullivan ◽  
Ana Holley ◽  
Kathryn Hally ◽  
Scott Harding ◽  
Peter Larsen
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Extracellular Matrix ◽  
Factor Analysis ◽  
Exploratory Factor Analysis

scholarly journals Transcriptomic profiling identifies candidate genes involved in salt tolerance of the xerophyte Pugionium cornutum

2019 ◽  
Author(s):  
Yan-Nong Cui ◽  
Fang-Zhen Wang ◽  
Cheng-Hang Yang ◽  
Jian-Zhen Yuan ◽  
Huan Guo ◽  
...  
Keyword(s):  
Salt Stress ◽  
Salt Tolerance ◽  
Candidate Genes ◽  
Molecular Mechanisms ◽  
Carbon Fixation ◽  
Assimilation Efficiency ◽  
Carbon Assimilation ◽  
Inorganic Ions ◽  
Ros Scavenging ◽  
Genes Encoding

Abstract Background: Pugionium cornutum is a xerophytic plant that primarily adapts to salt stress by accumulating inorganic ions (e.g., Cl-) for osmoregulation, improving its reactive oxygen species (ROS)-scavenging ability and maintaining high photosynthetic carbon assimilation efficiency, but the associated molecular mechanisms still remain unclear. Results: Here, we present an analysis of gene responses to salt stress based on the transcriptome of P. cornutum exposed to 50 mM NaCl treatment. The data revealed that, after NaCl treatment for 6 or 24 h, the transcript levels of multiple genes encoding proteins facilitating Cl- accumulation and NO3- homeostasis such as SLAH1, CLCg, CCC1, and NPF6.4, as well as the transport of other major inorganic osmoticums were significantly upregulated in roots and shoots, which should be favorable to enhancing osmotic adjustment capacity and maintaining the plant uptake and transport of nutrient elements; a large number of genes related to ROS-scavenging pathways were also significantly upregulated, which should be beneficial for mitigating salt-induced oxidative damage to the cell metabolism. Meanwhile, many genes encoding components of the photosynthetic electron transport and carbon fixation enzymes were significantly upregulated in shoots after salt treatment, possibly resulting in a high carbon assimilation efficiency in P. cornutum. Additionally, numerous salt-inducible transcription factor genes probably regulating the abovementioned processes were found. Conclusion: Candidate genes involved in salt tolerance of P. cornutum were identified, which lays a preliminary foundation for clarifying the molecular mechanism of the xerophytes adapting to harsh environments.

scholarly journals RELATIONSHIPS BETWEEN MARKERS OF EXTRACELLULAR MATRIX DEGRADATION AND SYSTEMIC INFLAMMATORY RESPONSE AMONG PATIENTS WITH ACUTE MYOCARDIAL INFARCTION

2020 ◽  
Vol 44 (1) ◽  
pp. 25-31
Author(s):  
E. V. Sid ◽  
V. V. Litvinenko
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Extracellular Matrix ◽  
Inflammatory Response ◽  
Matrix Metalloproteinase ◽  
Systemic Inflammatory Response ◽  
Matrix Metalloproteinase 2 ◽  
Control Group ◽  
Matrix Degradation ◽  
Extracellular Matrix Degradation

Abstract Despite all the preventive, diagnostic and therapeutic possibilities of our time, diseases of the circulatory system are the leading causes of death among adult population both in the world and in Ukraine. Modern consensuses of the European society of Cardiology have recommendations with many years of based-on-evidence experience in the diagnosis of acute myocardial infarction. They note that biomarkers of myocardial necrosis must meet modern requirements of accuracy, reproducibility, and especially sensitivity and specificity. Now, together with classical markers of heart muscle damage, markers reflecting various pathogenetic directions of acute myocardial infarction are increasingly used in clinical practice; they include markers of myocardial dysfunction and markers of inflammatory process activation. Purpose of the study. Identify relationships between markers of the extracellular matrix degradation and systemic inflammatory response among patients with acute myocardial infarction. Materials and methods. Results of the study are based on data from a comprehensive survey of 305 IHD patients: 162 patients with STEMI, 81 individuals with NSTEMI, and the control group consisted of 62 patients with angina pectoris (functional class II and III for 31 people). The sample of patients was carried out in the period from 2015 to January 2018 on the basis of MI «Regional medical center of cardiovascular diseases» of the Zaporizhzhia regional Council. All 305 surveyed people were comparable in age, social status, and gender (with the ratio of men to women was 4 to 1). Results and discussion. The highest level of HS-CRP was in the group of STEMI patients and amounted to 10,91 (9,40–13,43) mg/l and significantly exceeded by 24% the level of this indicator in the group of NSTEMI patients – 8,80 (7,05–10,91) mg/l, (p < 0,05). The level of TNF-αwas significantly higher in the STEMI group of 2,10 (1,53–2,86) pg/ml versus 1,67 (1,09–2,20) pg/ml in the NSTEMI group of patients, (p < 0,05) and the leap rate was 2,4 times higher than the level of 0,89 (0,67–1,55) pg/ml in the group of patients with stable IHD (p <0,05). In both groups of AMI patients with both STEMI and NSTEMI, there was a significant increase in IL-6 levels compared to the group of patients with stable IHD, where this indicator was 2,26 (1,22–3,66) pg/ml, 5 and 3,2 times, respectively (p < 0,05). The IL-6/IL-10 ratio in the STEMI and NSTEMI groups was 2,78 (1,72–4,68) versus 1,82 (1,49–2,36), respectively, and was significantly 50,8% higher (p < 0,05). Reliable direct links were found between: the levels of MPP-9 and HF-CRP (R = +0,61, p = 0,001), the levels of MPP-9 and TNF-α (R = +0,62, p = 0,001), the level of MPP-9 and the IL-6/IL-10 ratio, the levels of TIMP-2 and CRP (R = +0,50, p = 0,001). Keywords: matrix metalloproteinase-9, tissue inhibitor of matrix metalloproteinase-2, acute myocardial infarction.

Ischemia, reperfusion and preconditioning: traditional and new approaches for treatment of myocardial infarction

2016 ◽  
Vol 14 (3) ◽  
pp. 3-11
Author(s):  
Abdrei V. Lyubimov ◽  
Petr D. Shabanov
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Clinical Trials ◽  
Animal Models ◽  
Clinical Efficacy ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Katp Channels ◽  
Instrumental Control ◽  
Pharmacological Preconditioning

The review is devoted to the questions of improvement of the efficacy of myocardial infarction treatment by means of pharmacological drugs possessing pre- or postconditioning effect. The proofs of clinical efficacy of reperfusional therapy of the myocardial infarction are observed using examples of adenosine, activators of KATP channels (diazoxide and nicorandil), opiates (fentanyl, morphine) and some other drugs. The data are analyzed from the point of modern view of molecular mechanisms of hypoxia, the findings of objective laboratory and instrumental control in therapy of myocardial infarction in differend known clinical trials. It is concluded that pharmacological preconditioning is perspective approach in therapy of the acute myocardial infarction both in animal models and in humans.

scholarly journals Genome-Wide Profiling of the Microrna Transcriptome Regulatory Network to Identify Putative Candidate Genes Associated with Backfat Deposition in Pigs

Animals ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. 313 ◽  
Author(s):  
Xin Liu ◽  
Jianfei Gong ◽  
Ligang Wang ◽  
Xinhua Hou ◽  
Hongmei Gao ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Regulatory Networks ◽  
Molecular Mechanisms ◽  
Molecular Genetic ◽  
Subcutaneous Fat ◽  
Fat Deposition ◽  
Backfat Thickness ◽  
Feed Conversion ◽  
Protein Coding ◽  
Genes Encoding

Backfat deposition is strongly related to carcass traits, growth rate, feed conversion rate, and reproductive performance in pig production. To understand the molecular mechanisms underlying porcine backfat thickness phenotypes, transcriptome and miRNA profiling of backfat from high-backfat thickness and low-backfat thickness pigs were performed by RNA sequencing. Twenty genes encoding for miRNAs and 126 genes encoding for protein-coding genes were found to be differentially expressed between the two libraries. After integrative analysis of DEMs targets and DEGs, a total of 33 mRNA‒miRNA interaction pairs were identified, and the regulatory networks of these pairs were determined. Among these genes, five (AQP9, DKK3, GLYCTK, GLIPR1, and DUSP2) related to fat deposition were found to be strong candidate genes, and mir-31-5p/AQP9 and mir-31-5p/GLIPR1 may play important roles in fat deposition. Additionally, potential adipogenesis-related genes and miRNAs were identified. These findings improve the current understanding of the molecular genetic mechanisms of subcutaneous fat deposition in pigs and provide a foundation for further studies.

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