Abstract:We aimed to clarify the different angiogenesis effects of mini-tyrosyl-tRNA synthetase (TyrRS)/minitryptophanyl-tRNA synthetase (TrpRS) in rodent primates with acute myocardial infarction, by delivering small interfering RNAs (siRNAs) systemically in a liposomal formulation. Left coronary artery ligation was used to establish the model of acute myocardial infarction in rats; mini-TyrRS/mini-TrpRS-specific siRNAs were encapsulated in stable nucleic acid lipid particles (SNALP), and administered by intravenous i… Show more
“…Intramyocardial injection of plasmid DNA has the capacity for direct delivery of a gene to precisely defined regions. However, the weak transfection efficiency of nonviral gene transfection is still limiting for in vivo use [1,2].…”
This study presents a novel method that direct intramyocardial injection of low-dose plasmid DNA and microbubbles combined with insonation could further augment gene expression in normal and ischemic canine myocardium. Plasmids encoding enhanced green fluorescent protein (pEGFP) and hepatocyte growth factor (pHGF) (500 μg) were individually mixed with 0.5 ml of microbubble solution (MB) and injected into the normal or acute ischemic canine myocardium. The dogs in the plasmid + MB/US group underwent insonation (US). Other dogs were randomly divided into three treatment groups: plasmid and insonation, plasmid and MB injection, and plasmid injection only. The EGFP and HGF mRNA expressions were assessed in the myocardium at the injection site and at sites 0.5 and 1 cm remote from the injection site. Compared to plasmid transfer alone, a mean 13.4-fold enhancement of gene expression was achieved in the EGFP + MB/US group at 48 h (p < 0.01). HGF mRNA expression in ischemic zones was markedly elevated after 28 days, with a mean 9.0-fold enhancement in the HGF + MB/US group (p < 0.01). EGFP protein expression was detected in the normal myocardium at 1 cm remote from the injection site in the EGFP + MB/US group. Similarly, HGF protein expression was detected in the ischemic myocardium at 0.5 cm remote from the injection site in the HGF + MB/US group. These findings indicate that the radius of gene expression was partly extended in the two plasmid + MB/US groups. The capillary density increased from 20.9 ± 5.3/mm(2) in control myocardial infarction dogs without treatment to 126.7 ± 38.2/mm(2) in the HGF + MB/US group (p < 0.01). Taken together, the present data demonstrate that direct intramyocardial injection of an angiogenic gene and microbubbles combined with insonation can augment gene expression and angiogenesis. Consequently, this strategy may be a useful tool for gene therapy of ischemic heart disease.
“…Intramyocardial injection of plasmid DNA has the capacity for direct delivery of a gene to precisely defined regions. However, the weak transfection efficiency of nonviral gene transfection is still limiting for in vivo use [1,2].…”
This study presents a novel method that direct intramyocardial injection of low-dose plasmid DNA and microbubbles combined with insonation could further augment gene expression in normal and ischemic canine myocardium. Plasmids encoding enhanced green fluorescent protein (pEGFP) and hepatocyte growth factor (pHGF) (500 μg) were individually mixed with 0.5 ml of microbubble solution (MB) and injected into the normal or acute ischemic canine myocardium. The dogs in the plasmid + MB/US group underwent insonation (US). Other dogs were randomly divided into three treatment groups: plasmid and insonation, plasmid and MB injection, and plasmid injection only. The EGFP and HGF mRNA expressions were assessed in the myocardium at the injection site and at sites 0.5 and 1 cm remote from the injection site. Compared to plasmid transfer alone, a mean 13.4-fold enhancement of gene expression was achieved in the EGFP + MB/US group at 48 h (p < 0.01). HGF mRNA expression in ischemic zones was markedly elevated after 28 days, with a mean 9.0-fold enhancement in the HGF + MB/US group (p < 0.01). EGFP protein expression was detected in the normal myocardium at 1 cm remote from the injection site in the EGFP + MB/US group. Similarly, HGF protein expression was detected in the ischemic myocardium at 0.5 cm remote from the injection site in the HGF + MB/US group. These findings indicate that the radius of gene expression was partly extended in the two plasmid + MB/US groups. The capillary density increased from 20.9 ± 5.3/mm(2) in control myocardial infarction dogs without treatment to 126.7 ± 38.2/mm(2) in the HGF + MB/US group (p < 0.01). Taken together, the present data demonstrate that direct intramyocardial injection of an angiogenic gene and microbubbles combined with insonation can augment gene expression and angiogenesis. Consequently, this strategy may be a useful tool for gene therapy of ischemic heart disease.
“…In addition, it is headed to initiate clinical trials for the treatment of wet age-related macular degeneration or acute myocardial infarction [150] (http://www.pacificu.edu/optometry/ce/courses/20591/armdpg4. cfm; http://www.eyecyte.com/clinical.htm).…”
Although aminoacyl-tRNA synthetases (ARSs) and ARS-interacting multi-functional proteins (AIMPs) have long been recognized as housekeeping proteins, evidence indicating that they play a key role in regulating cancer is now accumulating. In this chapter we will review the conventional and non-conventional functions of ARSs and AIMPs with respect to carcinogenesis. First, we will address how ARSs and AIMPs are altered in terms of expression, mutation, splicing, and post-translational modifications. Second, the molecular mechanisms for ARSs' and AIMPs' involvement in the initiation, maintenance, and progress of carcinogenesis will be covered. Finally, we will introduce the development of therapeutic approaches that target ARSs and AIMPs with the goal of treating cancer.
“…Theoretically, the transplantation of BMSCs via the vein is the most safe way, and can promote angiogenesis, increase local myocardial perfusion and strengthen left ventricular function. [19] Some investigators emphasized the safety of intravenous transplantation of BMSCs, the number of transplanted BMSCs and the mechanisms underlying the therapeutic effect of BMSC transplantation on MI. Following intravenous injection, the BMSCs can migrate into multiple organs and systems via the circulation.…”
BACKGROUND:Intravenous transplantation has been regarded as a most safe method in stem cell therapies. There is evidence showing the homing of bone marrow stem cells (BMSCs) into the injured sites, and thus these cells can be used in the treatment of acute myocardial infarction (MI). This study aimed to investigate the effect of intravenous and epicardial transplantion of BMSCs on myocardial infarction size in a rabbit model.
METHODS:A total of 60 New Zealand rabbits were randomly divided into three groups: control group, epicardium group (group I) and ear vein group (group II). The BMSCs were collected from the tibial plateau in group I and group II, cultured and labeled. In the three groups, rabbits underwent thoracotomy and ligation of the middle left anterior descending artery. The elevation of ST segment >0.2 mV lasting for 30 minutes on the lead II and III of electrocardiogram suggested successful introduction of myocardial infarction. Two weeks after myocardial infarction, rabbits in group I were treated with autogenous BMSCs at the infarct region and those in group II received intravenous transplantation of BMSCs. In the control group, rabbits were treated with PBS following thoracotomy. Four weeks after myocardial infarction, the heart was collected from all rabbits and the infarct size was calculated. The heart was cut into sections followed by HE staining and calculation of infarct size with an image system.
RESULTS:In groups I and II, the infarct size was signifi cantly reduced after transplantation with BMSCs when compared with the control group (P<0.05). However, there was no signifi cant difference in the infarct size between groups I and II (P>0.05).CONCLUSION: Transplantation of BMSCs has therapeutic effect on MI. Moreover, epicardial and intravenous transplantation of BMSCs has comparable therapeutic efficacy on myocardial infarction.
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