CI Insight: Slow release of two drugs to protect the heart from heart disease!

, June 29, 2020 /PRNewswire/
Bio Valley --In two animal models, a new treatment reduces heart damage after a serious heart attackInjection of two chemicals in the form of slow release significantly reduced the size of the dead heart tissue, the infarction, and improved the function of the left ventricle, compared to the subjects who were not treatedthe risk of death in patients after an acute heart attack is directly related to the size of the infarction, it is valuable to reduce the size of the infarctionPatients with heart attacks form scar tissue instead of dead and dead heart muscle tissue, and over time, as the damaged heart struggles to maintain its ability to pump blood, it usually occursThe study of the new treatment at the University of Alabama at Birmingham (UAB) was published in JCI Insight, led by DrGianyi "Jay" Zhang and M.DWuqiang ZhuProfessor Zhang is a professor and dean of the Department of Biomedical Engineering at UAB Medical School and EngineeringPicture Source:JCI Insightthese two chemicals are FGF1 and CHIR99021 (CHIR)FGF1 is a fibroblast growth factor, CHIR is the activator of the Wnt signaling pathway, which is a set of signal transduction pathways that begin with the transmission of signals to proteins in cells through cell surface receptorsBoth drugs each showed some benefits, but have never been tested in a coordinated wayshortly after an experimental heart attack in mice and pigs, Zhang and his colleagues encapsulated FGF1 and CHIR in polylactic acid-ethanol acidnano-
particles and injected nano-
particles into the edge of the infarction The pig's heart is closer in size and biology to the human heart They found that nanoparticles slowly released both chemicals over a four-week period in both models, compared to the untreated control group, the therapy improved heart function, reduced the size of fibrosis scars, strongly stimulated the growth of blood vessels in the left ventricle, and prevented apoptosis (i.e procedural cell death) near the infarction zone UAB researchers also found that the therapy promotes the cell cycles of endothelial and smooth muscle cells, both in animals and in cultures "As far as we know, these data are the first to demonstrate that combining CHIR and FGF1 in the body can protect the heart, which can be demonstrated by significantly reducing the area of infarction and improving left ventricle function," Zhang said Saving doomed heart muscle cells remains the most important goal in cardiovascular science, given the low rate of myocardial cell regeneration in the heart of adult mammals UAB's team began screening chemicals that enhance the cycle of myocardial cells induced by human pluripotent stem cells They found that the combination of CHIR99021 and FGF1 at a certain concentration was the most effective treatment for inducing cell cycles They encapsulated two chemicals in nanoparticles, showing their release dynamics and showing that four different types of cells absorbed the nanoparticles at similar rates Picture Source: JCI Insight When researchers tested the results of injecting nanoparticles into the heart in a model of heart disease in pigs and mice, they were surprised by the results: the cell cycles of myocardial cells in the blank control group were negligible compared to the drugs screened to explore the potential mechanisms of heart protection in animal models, they found that CHIR-FGF1 nanoparticles enhance dating out the cell cycles of cell petri endothelial and smooth myovascular cells The researchers found that after the nanoparticles were processed, the transcription of genes involved in angiogenesis, cell proliferation, cell aging, and death in human umbilical venous endothelial cells changed They also found that in the cells they treated, the cell cycle regulates the increased level of proteins Professor Zhang said: "It is important to note that it is reported that apoptosis peak sefarction early after infarction, which may help prove the efficacy of these two chemicals, as they are used in acute injury, but it remains to be determined whether similar improvements can be achieved by delaying treatment until a slower stage." " (Bioon.com)
:
Slow release of two chemicals protects the heart after experimental heart attacks
Chengming Fan et al,
Myocardial protection by nanomaterials formulated with CHIR99021 and FGF1
, JCI Insight (2020) DOI: 10.1172/jci.insight.132796