WO2020085545A1 - Recombinant protein for prevention or treatment of myocardial infarction and composition comprising same for prevention or treatment of myocardial infarction - Google Patents

Abstract

The present invention relates to a recombinant protein for prevention or treatment of myocardial infarction, which is recombined on the basis of milk fat globule-EGF factor 8 (MFG-E8) protein and has the amino acid sequence of SEQ ID NO: 1. The recombinant protein can provide an excellent antifibrotic effect on the heart tissue of a subject to be treated in which remodeling progresses with fibrosis induced by myocardial infarction, thereby restoring the heart size and the function of heartbeat to normal levels. In addition, the present invention relates to a pharmaceutical composition comprising as an active ingredient a recombinant protein for prevention or treatment of myocardial infarction, which is recombined on the basis of milk fat globule-EGF factor 8 (MFG-E8) protein and has the amino acid sequence of SEQ ID NO: 1.

Description

Recombinant protein for preventing or treating myocardial infarction and composition for preventing or treating myocardial infarction comprising the same

The present invention relates to a recombinant protein for preventing or treating myocardial infarction and a composition for preventing or treating myocardial infarction comprising the same.

Myocardial infarction is one of the ischemic heart diseases that causes pain due to the fact that the coronary arteries of the heart are completely blocked by blood clots, and part of the heart muscle is destroyed or necrotic, preventing the flow of blood in the blood vessels.

Heart disease, such as myocardial infarction, is the number one mortality rate in the world. In particular, myocardial infarction has no cure and is not easy to transplant like other organs.

Drugs used mainly for the treatment of myocardial infarction currently use aspirin, clopidogrel, beta blockers, ace inhibitors, and angiotensin blockers. It is just slowing down.

Recently, a therapeutic agent for myocardial infarction prepared in the form of transplantation of adult stem cells or transplantation of myocardial cells using stem cells has been developed, but the effect is insufficient.

In addition, prior literature on the prior art related to the cell-type therapeutic agent provided for the treatment of myocardial infarction includes "Registration of dendritic cells for immune tube for the treatment of myocardial infarction and its manufacturing method" (hereinafter referred to as 'prior art') Is called).

In the case of the conventional pharmaceutical composition prepared for the treatment of myocardial infarction, including the prior art, the myocardial infarction necroticized by the myocardial infarction is unable to perform the fundamental myocardial infarction treatment through the treatment of damaged myocardial cells. There was a problem that the tissue was replaced, and as a result, the heart became enlarged, the normal cardiac function was lost, and the patient eventually died.

In addition, in the case of the pharmaceutical composition prepared for the treatment of myocardial infarction, including the prior art, the biocompatibility of the composition based on the chemical component is low, the incidence of side effects is high, and it suffers from mass production and quality control considering productivity. have.

The present invention was created to solve the above problems, and an object of the present invention is to fundamentally treat myocardial cell tissues that have undergone fibrosis and have undergone fibrosis, thereby restoring pulsatile functionality to normal levels, and furthermore, enlargement of the heart. It is to provide a composition containing a recombinant protein and the same for preventing or treating myocardial infarction that can be prevented.

In order to achieve the above object, the recombinant protein for preventing or treating myocardial infarction according to the present invention is a milk fat globule-EGF factor 8 (MFG-E8) protein-based recombinant protein, and consists of an amino acid sequence of SEQ ID NO: 1.

Here, the milk fat globule-EGF factor 8 (MFG-E8) protein-based recombinant protein for the prevention or treatment of myocardial infarction consisting of the amino acid sequence of SEQ ID NO: 1 is the left ventricular ejection fraction (EF, Ejection Fraction) of the heart to be prevented or treated ) Can be significantly increased.

In addition, the recombinant protein for the prevention or treatment of myocardial infarction consisting of the amino acid sequence of SEQ ID NO: 1 by recombination based on the milk fat globule-EGF factor 8 (MFG-E8) protein is a fraction of the left ventricular fraction of the heart to be prevented or treated (FS, Fractional shortening) can be significantly increased.

In addition, the recombinant protein for the prevention or treatment of myocardial infarction consisting of the amino acid sequence of SEQ ID NO: 1 that is recombinant based on Milk fat globule-EGF factor 8 (MFG-E8) protein is administered intralesionally, intravascularly, subcutaneously, or intranasally. Or it can be formulated for intraperitoneal administration.

On the other hand, in order to achieve the above object, the composition for preventing or treating myocardial infarction according to the present invention is a milk fat globule-EGF factor 8 (MFG-E8) protein-based recombination to prevent myocardial infarction consisting of the amino acid sequence of SEQ ID NO: 1 The recombinant protein for treatment is included as an active ingredient.

In addition, in order to achieve the above object, the present invention is a gene encoding a recombinant protein for preventing or treating myocardial infarction consisting of an amino acid sequence of SEQ ID NO: 1 that is recombined based on the milk fat globule-EGF factor 8 (MFG-E8) protein. It provides as another aspect.

In addition, in order to achieve the above object, the present invention includes a gene encoding a recombinant protein for preventing or treating myocardial infarction consisting of an amino acid sequence of SEQ ID NO: 1 by recombination based on the Milk fat globule-EGF factor 8 (MFG-E8) protein. The recombinant vector is provided as another aspect.

According to the present invention has the following effects.

First, through the recombinant protein for preventing or treating myocardial infarction, the heart size and heartbeat function can be restored to a normal level by providing an excellent anti-fibrotic effect to the heart tissue of a treatment target undergoing remodeling through fibrosis through myocardial infarction.

Second, it is possible to significantly increase the left ventricular ejection fraction (EF) of the target heart, which has been remodeled through fibrosis due to myocardial infarction through a recombinant protein for preventing or treating myocardial infarction.

Third, by using a recombinant protein for preventing or treating myocardial infarction, fractional shortening (FS) of the target heart, which has undergone remodeling through fibrosis due to myocardial infarction, can be significantly increased.

Fourth, due to the administration of a recombinant protein for the prevention or treatment of myocardial infarction, no serious serious pathological symptoms of the treatment target undergoing remodeling through fibrosis due to myocardial infarction are caused.

Fifth, it is possible to provide a recombinant protein for preventing or treating myocardial infarction, which is bio-friendly and has fewer side effects, and a composition comprising the same.

Sixth, it is possible to provide a recombinant protein for preventing or treating myocardial infarction and a composition containing the same for easy mass production and quality control.

1 shows the structure of a backbone vector in which a gene encoding a recombinant protein (NP-011) for preventing or treating myocardial infarction of the present invention is inserted.

Figure 2 can be inserted into the structure of the Backbone Vector shown in Figure 1, shows the DNA sequence of the gene encoding a recombinant protein for preventing or treating myocardial infarction (NP-011) of the present invention.

Figure 3 shows the amino acid sequence of a recombinant protein (NP-011) for the prevention or treatment of myocardial infarction of the present invention.

Figure 4 is a schematic diagram showing the design of the effect verification test for recombinant protein (NP-011) for the prevention or treatment of myocardial infarction of the present invention.

Figure 5 is a graph showing the measurement results of the second week left ventricular ejection fraction (EF) and fractional shortening rate (FS) of animal experimental models designed to verify the effect of the recombinant protein for preventing or treating myocardial infarction (NP-011) of the present invention to be.

Figure 6 is a graph showing the results of measurement of the left ventricular ejection fraction (EF) and fractional shortening rate (FS) at week 4 of animal experimental models designed to verify the effect of the recombinant protein for preventing or treating myocardial infarction (NP-011) of the present invention to be.

7 is a graph showing the results of measurement of the left ventricular ejection rate (EF) and fractional shortening rate (FS) at week 8 of animal experimental models designed to verify the effect of the recombinant protein for preventing or treating myocardial infarction (NP-011) of the present invention. to be.

8 is a graph showing the results of measuring changes in left ventricular ejection fraction (EF) according to the progression time of animal experimental models designed to verify the effect of a recombinant protein for preventing or treating myocardial infarction (NP-011) of the present invention.

FIG. 9 is a graph showing the results of measuring changes in left ventricular fraction shortening rate (FS) according to the progression time of animal experimental models designed to verify the effect of recombinant protein for preventing or treating myocardial infarction of the present invention (NP-011).

Figure 10 is a graph showing the results of comparing the changes in body weight according to the treatment progress of animal experimental models designed to verify the effect of the recombinant protein for preventing or treating myocardial infarction (NP-011) of the present invention.

FIG. 11 is a photograph showing the results of staining of MT and H & E of cardiac tissues of animal experimental models designed to verify the effect of recombinant protein (NP-011) for the prevention or treatment of myocardial infarction of the present invention.

12 is a result of calculating the area value of the locally fibrous portion compared to the total area of the left ventricle based on FIG. 11 of animal experimental models designed for verifying the effect of the recombinant protein for preventing or treating myocardial infarction of the present invention (NP-011). It is a graph showing.

Preferred embodiments of the present invention will be described in more detail with reference to the accompanying drawings, but for the brevity of description, the already-known technical parts will be omitted or compressed.

1. Description of recombinant protein for preventing or treating myocardial infarction (NP-011)

The process of obtaining the recombinant protein for preventing or treating myocardial infarction according to the present invention (NP-011) and the structural characteristics of the obtained protein will be described in detail with reference to FIGS. 1 to 3 below.

(1) Obtaining recombinant protein for preventing or treating myocardial infarction (NP-011)

First, the process of expression of the recombinant protein for preventing or treating myocardial infarction (NP-011) will be described.For the improvement of the protein structure of Milk fat globule-EGF factor 8 (MFG-E8), Origene's MFG-E8 (NM_005928) Human cDNA Clone ( Cat. No. RG217163), which was used as a template and subjected to PCR to obtain DNA fragments as shown in FIG. 2 (see SEQ ID NO: 4).

Thereafter, the DNA fragment of FIG. 2 obtained through PCR amplification at the HindIII and SalI restriction sites (A portion of FIG. 1) of the pLFCF Vector, which is a Mammalian expression Vector of the structure as shown in FIG. 1 (see SEQ ID NO: 4). Proceed with cloning to insert.

Thereafter, plasmid DNA is extracted and transfected into HEK293 cells to collect the culture medium after 2 days, and immunoprecipitation reaction (IP, Immunoprecipitation) with FLAG resin is performed to prevent or treat myocardial infarction by Western Blotting. The expression of the recombinant protein corresponding to the protein (NP-011) is confirmed.

Next, the process of mass production of a recombinant protein for preventing or treating myocardial infarction (NP-011) will be described. After confirming expression, the plasmid DNA that has been confirmed is secured through Maxi prep, and HEK293 cells are prepared to prepare a large amount of plasmid DNA. It can be transduced into HEK293 cells to perform mass production of a recombinant protein corresponding to a recombinant protein for preventing or treating myocardial infarction (NP-011).

Next, to describe the purification process for the quality control of recombinant protein for preventing or treating myocardial infarction (NP-011), 10 CornST CellSTACK Cell Culture Chamers were prepared, coated with HEK293 cells, and 1600 μg of plasmid DNA and 3200 μl After mixing the Transfection Reagents of at room temperature for 15 minutes, transfection is performed.

After 4 hours of transduction, the culture medium was replaced and further cultured for 6 days, and the culture medium was collected 3 times every 2 days to perform Affinity-type protein purification from the collected culture medium.

In this purification process, since the FLAG gene is expressed in the C-terminal of each protein (refer to SEQ ID NO: 6), only the target protein is bound using FLAG affinity resin, and then washed with a washing buffer to wash the target protein. Excluded proteins can be removed.

Thereafter, only pure target protein was extracted using Elution Buffer, and then SDS-PAGE was performed to confirm the finally obtained protein, followed by Western blotting using Coomassie Blue staining and Anti-FLAG antibody. Through this, the production and purity of the target protein can be confirmed.

Based on such milk fat globule-EGF factor 8 (MFG-E8) protein, it is recommended for cloning, mass production and purification for expression of recombinant protein (NP-011) for prevention or treatment of myocardial infarction prepared by recombination. The series of specific processes described herein are not limited to this, and a level of technology known and apparent to those skilled in the art for the construction of specific amino acid sequence structures (SEQ ID NOs: 1 and 3) of the recombinant protein to be described below will be described. It can be implemented in various ways.

For example, the structure and transformation of the expression vector used for cloning of recombinant protein (NP-011) for prevention or treatment of myocardial infarction prepared based on milk fat globule-EGF factor 8 (MFG-E8) protein. Techniques such as performance targets, production conditions and forms, purification conditions and forms can be implemented in various ways.

In addition, DNA fragments (fragments) that are cloned into an expression vector in relation to expression of a recombinant protein for prevention or treatment of myocardial infarction (NP-011) prepared based on milk fat globule-EGF factor 8 (MFG-E8) protein The structure of) is also based on the structure of FIG. 2, but according to an embodiment, a specific DNA nucleotide sequence encoding a specific signal peptide may be additionally linked to DNA fragments.

(2) Structure of recombinant protein (NP-011) for preventing or treating myocardial infarction

Recombinant protein for prevention or treatment of myocardial infarction based on milk fat globule-EGF factor 8 (MFG-E8) protein, which is finally prepared through the processes of cloning, separation, production, and purification of the recombinant protein described above (NP-011) ) Has the amino acid sequence structure as shown in SEQ ID NO: 1 or FIG. 3 in the sequence listing below.

Characteristically, the recombinant protein for preventing or treating myocardial infarction based on the milk fat globule-EGF factor 8 (MFG-E8) protein (NP-011) is a structural component of the MFG-E8 protein, EGF-like Domain, C1 Domain, and C2 Domain. Heavy EGF-like Domain (see SEQ ID NO: 2) and C1 Domain (see SEQ ID NO: 3) are recombined into structures.

In other words, the recombinant protein for preventing or treating myocardial infarction based on the milk fat globule-EGF factor 8 (MFG-E8) protein of the present invention (NP-011) forms an amino acid sequence of "EGF-like Domain + C1 Domain". It is used as a basic structure, and is characterized in that the C2 domain is excluded from the structure.

The milk fat globule-EGF factor 8 (MFG-E8) protein-based recombinant protein for preventing or treating myocardial infarction (NP-011) of the present invention is a main active ingredient of a pharmaceutical composition used for preventing or treating myocardial infarction Can be used as

In addition, the milk fat globule-EGF factor 8 (MFG-E8) protein-based recombinant protein for preventing or treating myocardial infarction (NP-011) of the present invention and a pharmaceutical composition having the same as its main active ingredient are administered in lesions, blood vessels ( It can be formulated for intrathecal administration, subcutaneous administration, intranasal administration, intraperitoneal administration, or administration in specific tissues (left ventricular tissue).

Meanwhile, the recombinant protein for preventing or treating myocardial infarction based on the milk fat globule-EGF factor 8 (MFG-E8) protein of the present invention (NP-011) is cloned into an expression vector in relation to the expression of the recombinant protein described above. Corresponding to the scope of the structural embodiments of the fragments (fragments) may be made according to the implementation of additional linkage of a specific Signal Peptide structure.

For example, a specific Signal Peptide structure may be implemented in a form that is connected to the EGF-like domain tip by having an amino acid sequence such as "MPRPRLLAALCGALLCAPSLLVA" (see SEQ ID NO: 5), but is not limited thereto.

2. Description of the test results for the verification of the effect of recombinant protein for preventing or treating myocardial infarction (NP-011)

In relation to the milk fat globule-EGF factor 8 (MFG-E8) protein based myocardial infarction prevention or treatment recombinant protein (NP-011) of the present invention, verification of the effect level of myocardial infarction prevention or treatment due to the recombinant protein and The comparison of the effect with the MFG-E8 protein was confirmed through a test, and the following test methods were used for the purpose of defining properties by means obvious to those skilled in the art.

(1) Production and experimental design of myocardial infarction animal model

First, an animal model inducing acute myocardial infarction (AMI) using an 8-10 week old male rat weighing 180-200 g is produced.

Next, the experimental group, as shown in Figure 4, the normal (Normal) comparative animal model (first experimental group), acute myocardial infarction (AMI) induced rat animal model (second experimental group), acute myocardial infarction ( AMI) -induced rats infused with saline (PBS, Phosphate Buffered Saline) in an animal model (3rd experimental group) and MFG-E8 (Milk fat globule-EGF factor 8) in acute myocardial infarction (AMI) -induced rats The injected animal model (4th experimental group) and the acute myocardial infarction (AMI) -induced rat myocardial infarction prevention or treatment recombinant protein (NP-011) injected into animal model (5th experimental group) group It is preferable to conduct experiments using 5 rats per group, a total of 30 rats.

Here, acute myocardial infarction (AMI) -induced rat animal model (2nd experimental group) is mixed with ketamine (Ketamine) 60mg / kg and hydrochloride (Hydrochloride) 7.5mg / kg and injected into the rat intraperitoneally. After opening the chest through, the left coronary artery was tied using 6-0 silk suture to induce myocardial infarction.

Acute myocardial infarction (AMI) induced rat animal model (2nd experimental group) immediately underwent suture surgery immediately after myocardial infarction, saline (PBS), MFG-E8 or recombinant protein for prevention or treatment of myocardial infarction (NP-011) ) Injected animal model (3rd experimental group to 5th experimental group) immediately after induction of myocardial infarction, as shown in Fig. 4, saline (PBS), a recombinant protein for preventing or treating myocardial infarction (NP-011), or MFG-E8 was administered at 160 μg / kg, and suture surgery was performed to breed for 8 to 10 weeks, and functional verification tests were performed and each result was verified.

(2) Verification of cardiac rhythm improvement effect using echocardiography of myocardial infarction induced animal model

Milk fat globule-EGF factor 8 (MFG-E8) protein-based myocardial infarction prevention or treatment of the present invention in order to confirm the cardiac function improvement of the recombinant protein (NP-011), based on the electrocardiogram measurement of the left ventricle The yield rate (EF) and fractional shortening rate (FS) were confirmed.

First, each of the first experimental group and the fifth experimental group, which were previously set, were set for Day 0 (Day 0), Day 1 (Day1), Day 14 (Day 14), Day 28 (Day28), and Day 56 (Day56) for 8 weeks. The ECG was measured using a Vivid 7 (GE medical systems) system and a 10 MHz small linear array transducer (i13L, GE medical systems) for a total of five times.

Here, rats corresponding to each experimental group were injected intraperitoneally by mixing ketamine 60mg / kg and hydrochloride 7.5mg / kg, and then electrocardiogram during two consecutive cardiac cycles under complete anesthesia was measured. Therefore, it is preferable to use the average value.

Next, the ejection rate (EF) and fractional shortening rate (FS) of the left ventricle were calculated based on the ECG results measured using echocardiography of the first to fifth experimental groups to compare and analyze the mutual results.

Here, the fractional shortening (FS) of the left ventricle is measured by a representative cardiac contraction value, and the ejection fraction (EF) of the left ventricle is the end-diastolic volume and the end-systolic volume. volume).

Accordingly, the results of the ejection rate (EF) and fractional shortening rate (FS) of the left ventricle respectively derived based on the ECG results measured using echocardiography of the first to fifth experimental groups are shown in FIGS. 5 to 5 As shown in 9.

As shown in FIG. 5, when looking at the results of the ejection rate (EF) and fractional shortening rate (FS) of the left ventricle according to the electrocardiogram measurement of the second week (day 14) of the animal models of the first experimental group to the fifth experimental group, acute myocardial infarction Even when the recombinant protein for preventing or treating myocardial infarction (NP-011) of the present invention is injected into the (AMI) -derived rat, the levels of the ejection rate (EF) and fractional shortening rate (FS) of the left ventricle are experimental groups 4 to 4 It is similar to that of the experimental group, and it can be seen that no significant improvement was made compared to the normal level of the first experimental group.

 Thereafter, as shown in FIG. 6, the results of the ejection rate (EF) and fractional shortening rate (FS) of the left ventricle according to the 4th week (day 28) ECG measurement of the animal models of the first experimental group to the fifth experimental group, Acute myocardial infarction (AMI) induced rat myocardial infarction prevention or treatment of recombinant protein (NP-011) of the present invention, the level of left ventricular ejection rate (EF) and fractional shortening rate (FS) in the second experimental group It can be seen that a significant improvement is made compared to the normal level of the first experimental group.

Finally, as shown in Figure 7, looking at the results of the ejection rate (EF) and fractional shortening rate (FS) of the left ventricle according to the 8th week (day 56) ECG measurement of the animal models of the first experimental group to the fifth experimental group, Acute myocardial infarction (AMI) induced rat myocardial infarction prevention or treatment of recombinant protein (NP-011) of the present invention, the level of left ventricular ejection rate (EF) and fractional shortening rate (FS) in the second experimental group It can be seen that the heart function is restored to the normal level by showing a significant difference and showing a marked improvement compared to the fourth to fourth experimental groups, closer to each other than the normal level of the first experimental group, and having a significant meaning.

In order to confirm the above-described results more clearly, as shown in FIGS. 8 and 9, the changes in the ejection rate (EF) and fractional shortening rate (FS) of the left ventricle for each experimental group over time, acute myocardium Injecting the recombinant protein for preventing or treating myocardial infarction (NP-011) of the present invention in an infarct (AMI) -induced rat, shortening the ejection rate (EF) and fraction of the left ventricle compared to the fourth experimental group injected with MFG-E8 The level of the rate (FS) can be increased with greater certainty and a greater increase, providing a steady and fast recovery rate of the heart rate function and a high level of recovery close to the normal level.

(3) Examination of weight change in animal models of myocardial infarction

Milk fat globule-EGF factor 8 (MFG-E8) protein-based myocardial infarction prevention or treatment recombinant protein (NP-011) of the present invention was confirmed weight change during cardiac function improvement.

First, each of the second experimental group and the fifth experimental group, which were previously set up, is measured and graphed over a total of three times on the first day (Day1), the 28th (Day28), and the 56th (Day56) for 8 weeks. Did.

As a result, as shown in FIG. 10, the recombinant protein for preventing or treating myocardial infarction (NP-011) of the present invention was compared to a rat in which acute myocardial infarction (AMI) was induced compared to a rat in which acute myocardial infarction (AMI) was induced. In the case of infusion, it can be seen that no significant change in body weight was observed for 8 weeks, and thus there was no significant effect on body weight change.

This is acute myocardial infarction (AMI) induced rat myocardial infarction prevention or treatment recombinant protein (NP-011) of the present invention in the process of recovery of cardiac pulsating function, but does not show a serious pathological side effect. It was confirmed that it does not.

(4) Verification of antifibrotic effect through MT and H & E staining of myocardial infarction induced animal model

Cardiac tissue through MT staining and H & E staining to confirm the improvement of cardiac function of recombinant protein (NP-011) for prevention or treatment of myocardial infarction based on the milk fat globule-EGF factor 8 (MFG-E8) protein of the present invention Fibrosis levels were measured.

First, after analyzing the animal tissues of each of the first experimental group and the fifth experimental group, which were previously set up, after fixing the heart extracted from each rat that has undergone the eighth week to analyze the degree of heart tissue fibrosis, 4% paraformaldehyde is fixed. , Paraffin block is prepared and excised to a thickness of 4 μm to analyze the degree of fibrosis of the heart tissue through H & E staining and Masson's trichrome (MT) staining.

Here, Hematoxylin and Eosin purchased from Sigma were used for H & E staining, and Trichrome Stain Kit (HT15, Sigma-Aldrich) purchased from Sigma was used for MT staining.

In addition, a photograph of a heart tissue sample for each experimental group was obtained as shown in FIG. 11 through MT and H & E staining to calculate the area value of the locally fibrous portion compared to the total area of the left ventricle.

 In addition, the calculation of the area value of the locally fibrous portion compared to the total area of the left ventricle for each experimental group was performed using Mathworks' Matlab (R2018b) software, and the unit of the relative width was expressed as arbitrary unit (a.u.).

As described above, the results for the ratio of the fibrous area measured based on the 8th week heart tissue sample photograph of the first experimental group to the fifth experimental group of FIG. 11 are as shown in FIG. 12.

11 and 12, the degree of fibrosis of the heart tissue for each experimental group and the degree of increase in the size of the heart tissue undergoing remodeling through myocardial infarction can be confirmed.

Specifically, in the fifth experimental group in which the recombinant protein for prevention or treatment of myocardial infarction (NP-011) of the present invention was injected into a rat in which acute myocardial infarction (AMI) was induced, acute myocardial infarction (AMI) was induced. Compared to the 2nd experimental group, it shows an anti-fibrotic effect of about 80%.

In addition, in the case of the fifth experimental group in which the recombinant protein for preventing or treating myocardial infarction (NP-011) of the present invention was injected into a rat in which acute myocardial infarction (AMI) was induced, MFG in acute myocardial infarction (AMI) induced rats -Compared to the 4th experimental group injected with E8, it shows about 34% higher antifibrosis effect.

That is, the recombinant protein for preventing or treating myocardial infarction of the present invention (NP-011) prevents the fibrosis of various cardiac tissues including myocardial cell tissues that have undergone fibrosis by necrosis by myocardial infarction through providing an overwhelmingly excellent antifibrotic ability. Thus, the abnormality of the heartbeat function due to tissue fibrosis and the cardiac hypertrophy phenomenon can be solved and essential treatment of myocardial infarction can be achieved.

The embodiments disclosed in the present invention are not intended to limit the technical spirit of the present invention, but to explain them, and the scope of the technical spirit of the present invention is not limited by these embodiments. The scope of protection should be interpreted by the claims below, and all technical spirits within the scope equivalent thereto should be interpreted as being included in the scope of the present invention.

Claims (7)

1. Milk fat globule-EGF factor 8 (MFG-E8) protein-based recombinant protein, characterized by consisting of the amino acid sequence of SEQ ID NO: 1

   Recombinant protein for the prevention or treatment of myocardial infarction.
2. According to claim 1,

   The recombinant protein is characterized by increasing the left ventricular ejection fraction (EF, Ejection Fraction) of the heart to be prevented or treated

   Recombinant protein for the prevention or treatment of myocardial infarction.
3. According to claim 1,

   The recombinant protein is characterized by increasing the left ventricular fractional shortening rate (FS) of the heart to be prevented or treated.

   Recombinant protein for the prevention or treatment of myocardial infarction.
4. According to claim 1,

   The recombinant protein is formulated for intralesional administration, intravascular administration, subcutaneous administration, intranasal administration, or intraperitoneal administration.

   Recombinant protein for the prevention or treatment of myocardial infarction.
5. A composition for preventing or treating myocardial infarction comprising the recombinant protein for preventing or treating myocardial infarction according to any one of claims 1 to 4 as an active ingredient.
6. A gene encoding a recombinant protein for preventing or treating myocardial infarction according to any one of claims 1 to 4.
7. Recombinant vector comprising a gene encoding a recombinant protein for preventing or treating myocardial infarction according to any one of claims 1 to 4.

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