Canine Acute Myocardial Infarction In Vivo Detection by MRI with Gradient Echo Technique and Contribution of Gd-DOTA

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.

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Intramyocardial injection of hypoxia-preconditioned adipose-derived stromal cells treats acute myocardial infarction: an in vivo study in swine

Cell and Tissue Research ◽

10.1007/s00441-014-1975-9 ◽

2014 ◽

Vol 358 (2) ◽

pp. 417-432 ◽

Cited By ~ 6

Author(s):

Yiyao Jiang ◽

Pengyu Chang ◽

Yu Pei ◽

Baojiang Li ◽

Yongjun Liu ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Stromal Cells ◽

In Vivo Study ◽

Intramyocardial Injection ◽

Adipose Derived Stromal Cells

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Imaging and characterization of acute myocardial infarction in vivo by gated nuclear magnetic resonance.

Circulation ◽

10.1161/01.cir.69.1.125 ◽

1984 ◽

Vol 69 (1) ◽

pp. 125-130 ◽

Cited By ~ 106

Author(s):

G Wesbey ◽

C B Higgins ◽

P Lanzer ◽

E Botvinick ◽

M J Lipton

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Nuclear Magnetic Resonance ◽

Magnetic Resonance ◽

Nuclear Magnetic

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Ex vivo-expanded bone marrow CD34+ for acute myocardial infarction treatment: in vitro and in vivo studies

Cytotherapy ◽

10.3109/14653249.2011.597559 ◽

2011 ◽

Vol 13 (9) ◽

pp. 1140-1152 ◽

Cited By ~ 7

Author(s):

Monica Gunetti ◽

Alessio Noghero ◽

Fabiola Molla ◽

Lidia Irene Staszewsky ◽

Noeleen de Angelis ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Bone Marrow ◽

Ex Vivo ◽

In Vivo Studies

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Network pharmacology-based identification of major component of Angelica sinensis and its action mechanism for the treatment of acute myocardial infarction

Bioscience Reports ◽

10.1042/bsr20180519 ◽

2018 ◽

Vol 38 (6) ◽

Cited By ~ 6

Author(s):

Xiaowei Niu ◽

Jingjing Zhang ◽

Jinrong Ni ◽

Runqing Wang ◽

Weiqiang Zhang ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Er Stress ◽

Heart Function ◽

Network Pharmacology ◽

Angelica Sinensis ◽

Peroxisome Proliferator ◽

Multiple Targets

Background: To decipher the mechanisms of Angelica sinensis for the treatment of acute myocardial infarction (AMI) using network pharmacology analysis. Methods: Databases were searched for the information on constituents, targets, and diseases. Cytoscape software was used to construct the constituent–target–disease network and screen the major targets, which were annotated with the DAVID (Database for Annotation, Visualization and Integrated Discovery) tool. The cardioprotective effects of Angelica sinensis polysaccharide (ASP), a major component of A. sinensis, were validated both in H9c2 cells subjected to simulated ischemia by oxygen and glucose deprivation and in rats with AMI by ligation of the left anterior coronary artery. Results: We identified 228 major targets against AMI injury for A. sinensis, which regulated multiple pathways and hit multiple targets involved in several biological processes. ASP significantly decreased endoplasmic reticulum (ER) stress-induced cell death both in vitro and in vivo. In ischemia injury rats, ASP treatment reduced infarct size and preserved heart function. ASP enhanced activating transcription factor 6 (ATF6) activity, which improved ER-protein folding capacity. ASP activated the expression of p-AMP-activated protein kinase (p-AMPK) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α). Additionally, ASP attenuated levels of proinflammatory cytokines and maintained a balance in the oxidant/antioxidant levels after AMI. Conclusion:In silico analysis revealed the associations between A. sinensis and AMI through multiple targets and several key signaling pathways. Experimental data indicate that ASP protects the heart against ischemic injury by activating ATF6 to ameliorate the detrimental ER stress. ASP’s effects could be mediated via the activation of AMPK-PGC1α pathway.

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Abstract 365: Targeted Delivery of IGF-1 Following Acute Myocardial Infarction

Circulation Research ◽

10.1161/res.111.suppl_1.a365 ◽

2012 ◽

Vol 111 (suppl_1) ◽

Author(s):

Raffay S Khan ◽

Jay C Sy ◽

Milton Brown ◽

Mario D Martinez ◽

Niren Murthy ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Targeted Delivery ◽

Coronary Artery Ligation ◽

Nuclear Staining ◽

Post Injection ◽

Artery Ligation ◽

Intact Cells ◽

Double Stranded Dna

During acute myocardial infarction (MI) there is excessive necrosis of myocardial cells, leading to the release of large amounts of DNA, representing a potential target for drug delivery. Hoechst, a commonly used molecule for staining nuclei, binds to the minor groove of double-stranded DNA and can be functionalized to contain reactive groups such as free amines, sulfhydryls, and biotin moieties. Insulin-like growth factor-1 (IGF-1), a small molecule with a short half-life is protective immediately following MI, though there is potential for long-term toxicity and off-target effects. Therefore, we hypothesized that conjugating IGF-1 to Hoechst would increase targeting of IGF-1 to the injured myocardium. Hoechst-IGF1 (H-IGF1) was synthesized by binding Hoechst-biotin to biotinylated IGF-1 via a fluorescent streptavidin linker. Intact cells did not show nuclear staining with H-IGF1, while permeabilized cells had a significant increase in blue fluorescent Hoechst staining, indicating H-IGF1 was cell impermeable but could still bind DNA. Activity of H-IGF1 was demonstrated by Akt phosphorylation in cultured cardiac progenitor cells and was similar to native IGF-1. To determine in-vivo targeting of H-IGF1 to MI, mice underwent 30 minutes of coronary artery ligation followed by reperfusion (I/R). Six hours following MI, mice were injected intravenously with 70ng of H-IGF1, S-IGF1 (streptavidin bound IGF-1 only) or PBS followed by in vivo imaging at 30 and 120 minutes post-injection. At 30 minutes post-injection, we found 3.2% (2.2 of 70ng) of the injected dose of H-IGF1 in infarcted hearts compared with 1.8% (1.3 of 70ng) of S-IGF1 (n=5-7; p<0.05). To confirm that targeting of H-IGF1 was dependent on binding DNA, H-IGF1 pre-bound to double-stranded DNA was injected intravenously after I/R. This led to a significant (p<0.05) decrease in targeted IGF-1 levels. IGF-1 levels determined by ELISA 2 hours post-injection demonstrated a similar trend with increased targeting of H-IGF1 compared with S-IGF1 treated mice (4.2±0.6 ng vs. 2.4±0.2 ng; p<0.05). In conclusion, our data demonstrate that intravenous delivery of Hoechst-conjugated IGF-1 increases myocardial targeting. This provides a novel strategy for delivery of growth factors for the treatment of MI.

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Effects of Sodium Nitroprusside on Platelet Adhesion, Subsequent Aggregation and Vasoconstriction

10.1055/s-0039-1682743 ◽

1977 ◽

Author(s):

H.R. Baumgartner

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Sodium Nitroprusside ◽

Platelet Adhesion ◽

Ex Vivo ◽

Balloon Catheter ◽

Strong Inhibitor ◽

Induced Aggregation

Sodium nitroprusside (SNP), a potent vasodilator, has shown beneficial effects in acute myocardial infarction. Since platelets may play an important role in the pathogenesis of myocardial infarction, the effect of SNP on their interaction with rabbit aorta subendothelium was investigated in vivo and under controlled blood flow conditions ex vivo and in vitro.One iliac artery and the abdominal aorta were denuded of endothelium by balloon catheter injury during infusion of glucose, SNP at 6 or 12 μg/kg/min in groups of 12, 6 and 7 rabbits respectively. The aorta and their branches were perfuse-fixed under controlled pressure 10 min after denudation. Morphometric evaluation showed dose-dependent and significant (2p < 0.01 or 0.001) inhibition of platelet spreading, adhesion and aggregation. The latter was abolished at the higher dose of SNP. Denudation and subsequent platelet adhesion caused strong vasoconstriction (2p < 0.001) which was inhibited by SNP (2p < 0.01).By exposure of subendothelium to either citrated blood or native blood in a flow chamber (2000 sec-1 shear rate) strong inhibition of spreading and adhesion-induced aggregation was again demonstrated at 6 and 12 μg/kg/min SNP. In vitro, adhesion-induced aggregation was completely abolished after the addition of SNP to rabbit (at 20 μg/ml) or human blood (2 μg/ml). 1 μg/ml PGE1 was needed to induce a similar inhibitory effect.Thus SNP is a strong inhibitor of platelet function and of injury + platelet induced vasoconstriction. These findings may explain its beneficial effect in acute myocardial infarction.

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