THE EFFICACY AND RELATIVE FIBRIN SELECTIVITY OF PROUROKINASE IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION

1987 ◽  
Author(s):  
J Loscalzo
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Degradation Products ◽  
Coronary Thrombosis ◽  
Therapeutic Option ◽  
Human Kidney ◽  
Thrombolytic Agents ◽  
Hemorrhagic Complications

The use of thrombolytic agents in acute myocardial infarction has gained widespread acceptance as an important early therapeutic option. Acute coronary thrombosis has been found in approximately 80% of patients with acute infarction and the use of standard thrombolytic agents opens these occluded vessels in most cases. Unfortunately, in many individuals standard agents also produce a systemic lytic state with its attendant hemorrhagic complications. Prourokinase (PUK) has been shown to be a relatively fibrin selective thrombolytic agent in vitro owing to its localized conversion to urokinase at the clot surface. Because of this desirable property, we studied the efficacy and selectivity of PUK in vivo in 19 patients with acute myocardial infarction. Each of these patients was documented by angiography to have a totally occluded infarct-related artery. Each patient was treated within six hours (range: 2 to 5.8 hours) of the onset of symptoms with 62.5 mg of PUK derived from the human kidney cell line, TCL598, infused intravenously over 90 minutes. Complete vessel patency was achieved in nine patients within 61 ± 19 minutes of the start of the infusion without apparent hemorrhagic complications. We evaluated the effect of PUK on fibrinogen, on nonspecific fibrinogen degradation products (FDP) the the fibrinogen/fibrin I peptide, Bβ 1-42, as well as on the specific fibrin degradation products, D-dimer (XDP) and the fibrin II peptide, Bβ 15-42. Values for these parameters measured before and at the end of the 90-minute infusion of PUK are given as the mean ± S.E.M.We conclude that PUK is an effective agent with which to achieve coronary thrombolysis and that at the doses used in this study, it aDDears to be relatively fibrin selective.

scholarly journals Cardioprotective Effects of Puerarin-V on Isoproterenol-Induced Myocardial Infarction Mice Is Associated with Regulation of PPAR-Υ/NF-κB Pathway

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3322 ◽  
Author(s):  
Xuguang Li ◽  
Tianyi Yuan ◽  
Di Chen ◽  
Yucai Chen ◽  
Shuchan Sun ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Inflammatory Responses ◽  
Therapeutic Option ◽  
Crystal Form ◽  
Human Coronary Artery ◽  
Beneficial Effects ◽  
Ppar Γ ◽  
Cardioprotective Effects

Puerarin is a well-known traditional Chinese medicine which has been used for the treatment of cardiovascular diseases. Recently, a new advantageous crystal form of puerarin, puerarin-V, has been developed. However, the cardioprotective effects of puerarin-V on myocardial infarction (MI) heart failure are still unclear. In this research, we aim to evaluate the cardioprotective effects of puerarin-V on the isoproterenol (ISO)-induced MI mice and elucidate the underlying mechanisms. To induce MI in C57BL/6 mice, ISO was administered at 40 mg/kg subcutaneously every 12 h for three times in total. The mice were randomly divided into nine groups: (1) control; (2) ISO; (3) ISO + puerarin injection; (4–9) ISO + puerarin-V at different doses and timings. After treatment, cardiac function was evaluated by electrocardiogram (ECG), biochemical and histochemical analysis. In vitro inflammatory responses and apoptosis were evaluated in human coronary artery endothelial cells (HCAECs) challenged by lipopolysaccharide (LPS). LPS-induced PPAR-Υ/NF-κB and subsequently activation of cytokines were assessed by the western blot and real-time polymerase chain reaction (PCR). Administration of puerarin-V significantly inhibits the typical ST segment depression compared with that in MI mice. Further, puerarin-V treatment significantly improves ventricular wall infarction, decreases the incidence of mortality, and inhibits the levels of myocardial injury markers. Moreover, puerarin-V treatment reduces the inflammatory milieu in the heart of MI mice, thereby blocking the upregulation of proinflammatory cytokines (TNF-α, IL-1β and IL-6). The beneficial effects of puerarin-V might be associated with the normalization in gene expression of PPAR-Υ and PPAR-Υ/NF-κB /ΙκB-α/ΙΚΚα/β phosphorylation. In the in vitro experiment, treatment with puerarin-V (0.3, 1 and 3 μM) significantly reduces cell death and suppresses the inflammation cytokines expression. Likewise, puerarin-V exhibits similar mechanisms. The cardioprotective effects of puerarin-V treatment on MI mice in the pre + post-ISO group seem to be more prominent compared to those in the post-ISO group. Puerarin-V exerts cardioprotective effects against ISO-induced MI in mice, which may be related to the activation of PPAR-γ and the inhibition of NF-κB signaling in vivo and in vitro. Taken together, our research provides a new therapeutic option for the treatment of MI in clinic.

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

Cytotherapy ◽  
2011 ◽  
Vol 13 (9) ◽  
pp. 1140-1152 ◽  
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

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

2018 ◽  
Vol 38 (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.

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

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.

Cathepsin L mediates intracellular ileal digestion of gastric intrinsic factor

1995 ◽  
Vol 268 (1) ◽  
pp. G33-G40 ◽  
Author(s):  
M. M. Gordon ◽  
T. Howard ◽  
M. J. Becich ◽  
D. H. Alpers
Keyword(s):  
Degradation Products ◽  
Cathepsin L ◽  
Intrinsic Factor ◽  
Recombinant Baculovirus ◽  
Human Kidney ◽  
Intracellular Degradation ◽  
Basolateral Side ◽  
Renal Tubule Cell

Although acidic proteases of lysosomal origin are implicated in the degradation of intrinsic factor (IF) during cobalamin (cbl) transport across enterocytes and proximal renal tubule cell lines, the enzyme(s) involved in this process is not known. Recombinant (baculovirus-produced) rat 125I-labeled IF (125I-rIF), 43 kDa, added in vivo to the lumen of rat ileum was converted intracellularly to peptides of 33 and 26 kDa. In vitro rat 125I-rIF was degraded to peptides of 33 and 31 kDa by addition of cathepsin L; this conversion was fully inhibited by leupeptin. Western blot analysis using antiserum against denatured native rat IF identified additional cathepsin L degradation products in the 17- to 23-kDa range. In vitro the binding of cobalamin partially inhibited cathepsin L degradation of IF. Rat rIF produced from either insect (Sf9) or mammalian (CHO) cells and native rat IF were all degraded by cathepsin L, although the prominence of the various products differed in the recombinant preparations, being 33 and 36 kDa, respectively. Native rat IF was most sensitive to proteolysis, and no degradation products were identified. Rat 125I-rIF was taken up by LLC-PK1 cells, and 125I from degraded IF appeared abundantly on the basolateral side of cell monolayers by 1 h. The intracellular products of rat rIF in LLC-PK1 cells were the same size as those produced in vitro by the action of cathepsin L. Antiserum against a human kidney cDNA cathepsin L fusion protein easily demonstrated the protease in rat intestinal mucosa, as well as in all other tissues tested. These data suggest that cathepsin L is the protease responsible for the leupeptin-sensitive intracellular degradation of IF.

scholarly journals In Vivo and In Vitro Studies Support That a New Splicing Isoform of OLR1 Gene Is Protective Against Acute Myocardial Infarction

2005 ◽  
Vol 97 (2) ◽  
pp. 152-158 ◽  
Author(s):  
Ruggiero Mango ◽  
Silvia Biocca ◽  
Francesca del Vecchio ◽  
Fabrizio Clementi ◽  
Federica Sangiuolo ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
In Vitro Studies

scholarly journals Novel Fabrication of Engineered Nano-Selenium Incorporated Hydrogel for Potential Therapy and Care and of Acute Myocardial Infarction

2021 ◽  
Author(s):  
Jianmei Li ◽  
Pengfei Wang
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Modern Medicine ◽  
Spectroscopic Techniques ◽  
Cell Compatibility ◽  
Human Cardiomyocytes ◽  
Pharmaceutical Therapy ◽  
Long Time

Abstract Recent years, the cardiac vascular disease has arisen owing to acute myocardial infarction (MI) and heart failures leads to death worldwide. Various treatments are available for MI in modern medicine such as implantation of devices, pharmaceutical therapy, and transplantation of organs, nonetheless it has many complications to find an organs donor, devices for stenosis, high intrusiveness and long-time hospitalization. To overcome these problems, we have designed and developed a novel hydrogel material with combination of Se NPs loaded poly(ethylene glycol)/tannic acid (PEG/TA) hydrogel for the treatment of acute MI repair. Herein, Se NPs was characterized by the effective analytical and spectroscopic techniques. In vitro cell compatibility and anti-oxidant analyses were examined on human cardiomyocytes in different concentrations of Se NPs and appropriate Se NPs loaded hydrogel samples to demonstrate its greater suitability into in vivo cardiac applications. In vivo investigations of MI mice models injected with Se hydrogels established that LV wall thickness was conserved significantly from the value of 235.6 µm to 390 µm. Addition that, the relative scar thickness (33.6 %) and infarct size (17.1 %) of the MI model was enormously reduced after injection of Se hydrogel when compared to the Se NPs and control (MI) sample, respectively, which confirmed that Se introduced hydrogel have greatly influenced on the restoration of infarcted heart. Based on the investigated results of the nanoformulated samples, it could be a promising material for future generations treatment of acute myocardial infarction and cardiac repair applications.

scholarly journals LncRNA Chaer Prevents Cardiomyocyte Apoptosis From Acute Myocardial Infarction Through AMPK Activation

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhiyu He ◽  
Xiaojun Zeng ◽  
Deke Zhou ◽  
Peiying Liu ◽  
Dunzheng Han ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Heart Function ◽  
Glucose Deprivation ◽  
Cardiomyocyte Apoptosis ◽  
Oxygen Glucose Deprivation ◽  
Compound C ◽  
Life Threatening

Long non-coding RNA (lncRNA) is widely reported to be involved in cardiac (patho)physiology. Acute myocardial infarction, in which cardiomyocyte apoptosis plays an important role, is a life-threatening disease. Here, we report the lncRNA Chaer that is anti-apoptotic in cardiomyocytes during Acute myocardial infarction. Importantly, lncRNA Chaer is significantly downregulated in both oxygen-glucose deprivation (oxygen-glucose deprivation)-treated cardiomyocytes in vitro and AMI heart. In vitro, overexpression of lncRNA Chaer with adeno virus reduces cardiomyocyte apoptosis induced by OGD-treated while silencing of lncRNA Chaer increases cardiomyocyte apoptosis instead. In vivo, forced expression of lncRNA Chaer with AAV9 attenuates cardiac apoptosis, reduces infarction area and improves mice heart function in AMI. Interestingly, overexpression of lncRNA Chaer promotes the phosphorylation of AMPK, and AMPK inhibitor Compound C reverses the overexpression of lncRNA Chaer effect of reducing cardiomyocyte apoptosis under OGD-treatment. In summary, we identify the novel ability of lncRNA Chaer in regulating cardiomyocyte apoptosis by promoting phosphorylation of AMPK in AMI.

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