ABSTRACT
Background and Objectives@#Large clinical studies of sodium/glucose cotransporter 2 (SGLT2) inhibitors have shown a significant beneficial effect on heart failure-associated hospitalization and cardiovascular events. As SGLT2 is known to be absent in heart cells, improved cardiovascular outcomes are thought to be accounted for by the indirect effects of the drug. We sought to confirm whether such benefits were mediated through SGLT2 expressed in the heart using myocardial infarction (MI) model. @*Methods@#Mice pre-treated with empagliflozin (EMPA), an SGLT2 inhibitor, showed a significantly reduced infarct size compared with the vehicle group three days post-MI.Interestingly, we confirmed SGLT2 localized in the infarct zone. The sequential changes of SGLT2 expression after MI were also evaluated. @*Results@#One day after MI, SGLT2 transiently appeared in the ischemic areas in the vehicle group and increased until 72 hours. The appearance of SGLT2 was delayed and less in amount compared with the vehicle group. Additionally, there was a significant difference in metabolites, including glucose and amino acids in the 1 H nuclear magnetic resonance analysis between groups. @*Conclusions@#Our work demonstrates that SGLT2 is transiently expressed in heart tissue early after MI and EMPA may directly operate on SGLT2 to facilitate metabolic substrates shifts.
ABSTRACT
Background and Objectives@#Large clinical studies of sodium/glucose cotransporter 2 (SGLT2) inhibitors have shown a significant beneficial effect on heart failure-associated hospitalization and cardiovascular events. As SGLT2 is known to be absent in heart cells, improved cardiovascular outcomes are thought to be accounted for by the indirect effects of the drug. We sought to confirm whether such benefits were mediated through SGLT2 expressed in the heart using myocardial infarction (MI) model. @*Methods@#Mice pre-treated with empagliflozin (EMPA), an SGLT2 inhibitor, showed a significantly reduced infarct size compared with the vehicle group three days post-MI.Interestingly, we confirmed SGLT2 localized in the infarct zone. The sequential changes of SGLT2 expression after MI were also evaluated. @*Results@#One day after MI, SGLT2 transiently appeared in the ischemic areas in the vehicle group and increased until 72 hours. The appearance of SGLT2 was delayed and less in amount compared with the vehicle group. Additionally, there was a significant difference in metabolites, including glucose and amino acids in the 1 H nuclear magnetic resonance analysis between groups. @*Conclusions@#Our work demonstrates that SGLT2 is transiently expressed in heart tissue early after MI and EMPA may directly operate on SGLT2 to facilitate metabolic substrates shifts.
ABSTRACT
BACKGROUND AND OBJECTIVES: Poor homing efficiency is one of the major limitations of current stem cell therapy. Magnetic bionanoparticles (MPs) obtained from Magnetospirillum sp. AMB-1 have a lipid bilayer membrane and ferromagnetic properties. We evaluated a novel priming strategy using MPs to enhance the homing of transplanted progenitor cells to target tissue. MATERIALS AND METHODS: Effects of MP on proliferation, viability, and migration of late human endothelial progenitor cells (EPCs) were examined in vitro. Additionally, effects of MP on gene and protein expression related to survival and adhesion were evaluated. Homing and angiogenic efficiency of MP transferred late EPCs was evaluated in nude mouse hindlimb ischemia model. RESULTS: Below threshold concentration, MP transfer did not influence proliferation or survival of late EPCs, but enhanced migration and trans-endothelial migration of late EPCs toward magnet. Below threshold concentration, MP transfer did not influence gene and protein expression related to survival. In the mouse hindlimb ischemia model, late EPCs treated with high dose MP (5 ug/mL) showed enhanced homing of injected late EPCs in the ischemic limb by magnet, compared to low dose MP (1 ug/mL) treated late EPCs. In addition, high dose MP transferred EPC showed significantly better improvement of perfusion in ischemic limb compared to untreated EPC. CONCLUSION: MP transfer with magnet application can be a promising novel strategy to enhance homing efficacy and outcomes of current stem cell therapy.
Subject(s)
Animals , Humans , Mice , Extremities , Hindlimb , Ischemia , Lipid Bilayers , Magnetics , Magnetospirillum , Magnets , Membranes , Mice, Nude , Nanoparticles , Perfusion , Phosphorylcholine , Stem Cells , TransplantsABSTRACT
The surgical outcome of excimer laser photorefractive keratectomy(PRK) depends on the accuracy of ablation and the smoothness of the surface ablated. The purpose of this study was to investigate the clinical usefulness of a new eyeball fixation device(EK fixation device). First, the PRK was done on the cornea of New Zealand white rabbit (-8 D, 5.5 mm). The surface with the device was smoother compared to that without. Second, The PRK (-4 D, 6 mm)was done on the surface of the contact lens over the cornea of human volunteers. The ablation surface with the device was smoother than that without(0.20+/-0.04 micrometer vs. 0.34 +/-0.14 micrometer, p=0.028). The epithelial healing experiment in New Zealand white rabbit after myopic PRK (-8 D, 5.5 mm)showed more rapid wound healing in the fixation group (66.49+/-0.03 micrometer/hr vs 47.93+/-1.80 micrometer/hr, p=0.0001). In conclusion, the EK fixation device during the PRK procedures creates a smoother ablation surface and enhances corneal epithelial healing, thus may be a useful clinical device.
Subject(s)
Cornea , Healthy Volunteers , Lasers, Excimer , New Zealand , Wound HealingABSTRACT
PURPOSE: The purpose of this study is to clarify the degree of corneal neovascularization and its expression of MMP-2. 9(matrix metalloproteinase) and TIMP-1, 2(tissue inhibitor of metalloproteinases) according to the different concentrations of VEGF(vascular endothelial growth factor). METHODS: After the pellets with different amounts of VEGF(VEGF 125, 250 ng) were inserted into the corneal stroma of rat model, their degree of corneal neovascularization and the expression of MMP-2, 9 and TIMP-1, 2 were compared with those of control group where pellets were filled with phosphate-buffered saline. RESULTS: At the 7th day after the pellet insertion, degree of neovascularization was most highly scored in the group with pellet which contained the largest amount of VEGF, 250 ng, and there was statistically noticeable increase of eovascularization with the increase of VEGF amount(P<0.05). On immunohistochemical staining, as the amount of VEGF increases, not only MMP-2, 9 and flk-1, but also TIMP-1, 2 were expressed more. CONCLUSIONS: In conclusion, when it comes to neovascularization, MMP-2, 9, which induces angiogenesis, as well as its inhibitor TIMP-1, 2 are increased to maintain the homeostasis of the cornea.