Heparin Sulfate Proteoglycan Combined With Basic Fibroblast Growth Factor To Promote The Repair Of Myocardial Injury

Myocardial infarction(MI)is a global disease with a high morbidity and fatality.It is also the main cause of chronic heart failure,which seriously affects the quality of life of patients.Myocardial infarction is caused by various reasons,mainly through obstructing the coronary circulation of the heart,causing cardiocytes apoptosis and weakening the heart function.At present,clinical treatment mainly uses physical intervention methods to restore the normal operation of the coronary circulation by transplanting heart stents and building side branch artificial blood vessels.However,these interventions are not suitable for all heart patients,especially those who had have undergone multiple bypass surgery.Therefore,researches and developments of the treatment methods for patients with different heart diseases are imminent.Extracellular matrix(ECM)is a type of non-cellular components distributed in various tissues and organs.In addition to being an essential structural component,extracellular matrix molecules also play an important role in key cellular events.The occurrence and development of many diseases are closely related to changes in the composition of extracellular matrix,especially cardiovascular diseases.The study found that after the occurrence of myocardial infarction,cardiocytes apoptosis and cardiac extracellular matrix degradated,and collagen molecules deposited to form non-constrictive scar tissue,which caused non-adaptive changes in the shape,structure and function of the heart tissue.In order to further study the changes of tissue microenvironment after myocardial infarction,this study used transcriptome sequencing to analyze the effect of myocardial infarction on the gene level of cardiac extracellular matrix tissue.The analysis found that the expression of extracellular matrix molecules after myocardial infarction increased to varying degrees,but due to the large increase in collagen and other structural extracellular matrix molecules,especially heparin sulfate proteoglycan(HSPG)accounted for 8.8%of the normal tissue reduced to about 1%.HSPG is the main component of the extracellular matrix,which can be combined with a variety of extracellular matrix molecules,can also effectively bind various growth factors and promote the efficient binding of growth factors to receptors and signal transduction.Therefore,if HSPG is insufficient in the microenvironment after myocardial injury,it will lead to the inefficient effect of endogenous or exogenous growth factors,which is not conducive to tissue damage repair.It is well known that basic fibroblast growth factor(bFGF)promotes angiogenesis after various injuries,but due to diffusion,enzymatic digestion,and weak binding with co-receptors in vivo,it reduces its effective functioning of biological functions.Studies have found that HSPG can act as a co-receptor for bFGF and affect its biological activity to regulate a wide range of cell functions and biological processes.However,the effect of HSPG on the function of bFGF after myocardial infarction is unclear.In this study,exogenous HSPG and bFGF were injected into the rat heart together to deliver angiogenic growth factors for inducing ischemic heart repair after myocardial infarction.The biological mechanisms of HSPG binding with bFGF were further studied by cell adhesion assay,and assays of bFGF and matrix metalloproteinase 2(MMP2)activities demonstrated that HSPG enhances cell adhesion,promotes the bioactivity of bFGF in angiogenesis,and protects bFGF from enzymolysis.The specific binding of HSPG with bFGF protein was demonstrated,which was about 6-fold stronger than the binding of bFGF with heparin.Sustained release of bFGF from HSPG was observed in vivo and in vitro.Additionally,HSPG partly inhibited the proteolytic activity of matrix metalloprotein 2,thus protecting bFGF from enzymolysis.The bioactivity of bFGF was promoted when it was administered with HSPG as a co-receptor,and cardiomyocyte adhesion was enhanced.Furthermore,the HSPG combined with bFGF increased angiogenesis and promoted cardiomyocyte survival and recovery of cardiac function recovery following induced myocardial infarction.Our results indicate that HSPG has potential clinical utility as delivery agent for heparin-binding growth factors.This could represent a safe approach to encouraging angiogenesis in cardiac diseases.Therefore,extracellular proteins that mimic the bio-scaffold of the extracellular matrix could promote the activities of bFGF to facilitate ischemic heart repair.