CN-121992094-A - Molecular markers for diagnosis, prognosis evaluation and treatment of cardiac fibrosis

CN121992094ACN 121992094 ACN121992094 ACN 121992094ACN-121992094-A

Abstract

The invention relates to a molecular marker for diagnosis, prognosis evaluation and treatment of heart fibrosis, belonging to the technical field of biological medicine. The invention provides a molecular marker capable of diagnosing cardiac fibrosis, evaluating the severity of cardiac fibrosis, evaluating the prognosis of cardiovascular diseases associated with cardiac fibrosis or evaluating the prognosis of acute myocardial infarction, the molecular marker comprising hepatocyte growth factor. It was found that HGF was significantly elevated in the plasma of patients with cardiac fibrosis, as was the plasma HGF level before surgery in patients with aortic valve stenosis, and thus HGF could be used for diagnosing cardiac fibrosis and evaluating the severity of cardiac fibrosis. The research shows that the transient elevation of HGF in time in the plasma of patients with acute myocardial infarction is obviously related to good prognosis, and the sustained low-level elevation, the sustained high-level elevation, the recurrent elevation and the delayed elevation of HGF are obviously related to poor prognosis, so the HGF can be used for evaluating the prognosis of acute myocardial infarction.

Inventors

ZHAO YONG
CHENG ZHAOYUN
LIU FANGYAN
GE YINGHUI
LIN QING
Niu Yagun
YANG QINGDAN
QI XINLEI

Assignees

阜外华中心血管病医院
河南心血管病中心(国家心血管病中心华中分中心)

Dates

Publication Date: 20260508
Application Date: 20241108

Claims (10)

1. The molecular marker is characterized by comprising hepatocyte growth factor, and has any one of the following functions: (a) Diagnosing cardiac fibrosis; (b) Assessing the severity of cardiac fibrosis; (c) Assessing the prognosis of acute myocardial infarction; Or (d) assessing the prognosis of cardiovascular diseases other than acute myocardial infarction that are associated with cardiac fibrosis.
2. The molecular marker of claim 1, wherein the cardiac fibrosis comprises cardiac fibrosis caused by pressure loading and/or cardiac fibrosis caused by myocardial infarction; The cardiovascular diseases accompanied by heart fibrosis besides acute myocardial infarction comprise hypertension, diastolic heart failure, cardiomyopathy and/or sudden cardiac death.
3. Use of a reagent for detecting a molecular marker according to claim 1 or 2 in a sample to be tested for the preparation of a product, characterized in that said product has the functions as shown in any one of the following: (a) Diagnosing cardiac fibrosis; (b) Assessing the severity of cardiac fibrosis; (c) Assessing the prognosis of acute myocardial infarction; Or (d) assessing the prognosis of cardiovascular diseases other than acute myocardial infarction that are associated with cardiac fibrosis.
4. A product comprising a reagent for detecting the molecular marker according to claim 1 or 2 in a sample to be tested, said product having the functions as shown in any one of the following: (a) Diagnosing cardiac fibrosis; (b) Assessing the severity of cardiac fibrosis; (c) Assessing the prognosis of acute myocardial infarction; Or (d) assessing the prognosis of cardiovascular diseases other than acute myocardial infarction that are associated with cardiac fibrosis.
5. A predictive model, characterized in that it has the functions of any one of the following: (a) Diagnosing cardiac fibrosis; (b) Assessing the severity of cardiac fibrosis; (c) Assessing the prognosis of acute myocardial infarction; or (d) assessing the prognosis of cardiovascular disease associated with cardiac fibrosis other than acute myocardial infarction; the prediction model comprises a detection module, a data analysis module and a prediction module; the detection module is used for detecting the level of the molecular marker in the sample to be detected according to the claim 1 or 2; the data analysis module is used for analyzing the detection result output by the detection module; the prediction module is used for classifying whether the sample to be tested is ill or good or bad after prognosis according to the analysis result output by the data analysis module.
6. A drug screening method, characterized in that the drug comprises a drug for treating cardiac fibrosis, acute myocardial infarction and/or other cardiovascular diseases accompanied with cardiac fibrosis except for acute myocardial infarction; the method comprises the steps of administering a drug to be screened to a subject, obtaining the result of the subject after administration of the drug to be screened, which is related to the molecular marker of claim 1 or 2, and judging whether the drug to be screened is effective or ineffective according to the obtained result.
7. Use of hepatocyte growth factor, hepatocyte growth factor signal pathway blocker and/or neutrophil infiltration inhibitor for the manufacture of a medicament, characterised in that the medicament has any of the following functions: (a) Preventing and/or treating cardiac fibrosis; (b) Preventing and/or treating acute myocardial infarction; Or (c) preventing and/or treating cardiovascular diseases other than acute myocardial infarction accompanied by heart fibrosis.
8. The use according to claim 7, wherein the composition of the medicament comprises hepatocyte growth factor and/or hepatocyte growth factor signal path blockers when the medicament has the function of preventing and/or treating cardiac fibrosis or other cardiovascular diseases accompanied by cardiac fibrosis besides acute myocardial infarction; when the medicament has the function of preventing and/or treating acute myocardial infarction, the component of the medicament comprises hepatocyte growth factor, or the component of the medicament comprises hepatocyte growth factor signal path blocking agent and/or neutrophil infiltration inhibitor.
9. The use according to claim 7 or 8, wherein the treatment of acute myocardial infarction comprises treatment of acute myocardial infarction by controlling fibroblast proliferation leading to an acute inflammatory response and/or controlling myofibroblast-mediated fibrotic repair.
10. A medicament, characterized in that the medicament has any one of the following functions: (a) Preventing and/or treating cardiac fibrosis; (b) Preventing and/or treating acute myocardial infarction; Or (c) preventing and/or treating cardiovascular diseases other than acute myocardial infarction accompanied by heart fibrosis; The components of the medicine comprise hepatocyte growth factor, hepatocyte growth factor signal channel blocker and/or neutrophil infiltration inhibitor.

Description

Molecular markers for diagnosis, prognosis evaluation and treatment of cardiac fibrosis Technical Field The invention relates to a molecular marker for diagnosis, prognosis evaluation and treatment of heart fibrosis, belonging to the technical field of biological medicine. Background Cardiac fibrosis (also known as myocardial fibrosis) is characterized by excessive proliferation of cardiac fibroblasts and excessive production of extracellular matrix in myocardial tissue. Normally, the extracellular matrix provides mechanical support to the myocardial tissue. However, excessive or uncontrolled heart fibrosis can severely affect the systolic and diastolic functions of the heart, as well as the electrophysiological functions of the heart. Studies have shown that cardiac fibrosis is associated with almost all cardiovascular diseases, and therefore, clinically, a range of significant cardiovascular disease prognosis, including hypertension, diastolic heart failure, cardiomyopathy, sudden cardiac death, etc., can be determined based on the degree of cardiac fibrosis in the patient. It has also been confirmed that after acute myocardial infarction, the repair of fibrosis of the heart is extremely important for restoring cardiac function, and therefore, clinically, the prognosis of acute myocardial infarction can also be judged according to the occurrence of cardiac fibrosis of a patient. Cardiac fibrosis is extremely complex, mainly in two ways, first, it can occur at any stage of cardiovascular disease, and second, it involves multiple cell types. Although fibroblasts are the primary executive cells of cardiac fibrosis, other cell types also play an important role in the progression of cardiac fibrosis. Currently, fibrosis is studied mainly by isolating certain types of cells. Whereas myocardial tissue is rich in dense extracellular matrix, isolating cells by digestion affects gene expression. Because of these complications, current knowledge of cardiac fibrosis is not deep enough, so that at present, cardiac fibrosis still lacks effective treatment means, and there is also a lack of good intervention means on how to restore cardiac function by controlling cardiac fibrosis after acute myocardial infarction. At the same time, current clinical diagnosis of cardiac fibrosis relies largely on invasive tissue biopsies, or by cardiac magnetic resonance gadolinium delayed enhancement (LGE) and T1 mapping detection. Invasive tissue biopsies, among other things, often involve direct contact to tissues or organs, and patients may experience risk of pain, bleeding, infection or other complications, whereas cardiac magnetic resonance gadolinium delay enhancement (LGE) and T1 mapping tests are complex to operate, require high levels of expertise for the operator, and are expensive. If plasma markers with direct correlation with the occurrence and development of heart fibrosis can be found, the method is very helpful for clinical diagnosis of heart fibrosis. Several plasma markers associated with fibrosis have been reported to date, but these are neither cardiac-derived nor known to reflect a specific stage of fibrosis, and thus, at this stage, there is still a lack of plasma markers that can be used for clinical diagnosis of cardiac fibrosis. Disclosure of Invention In order to solve the problems, the invention provides a molecular marker, which comprises Hepatocyte Growth Factor (HGF), and has the functions as shown in any one of the following: (a) Diagnosing cardiac fibrosis (also known as myocardial fibrosis); (b) Assessing the severity of cardiac fibrosis; (c) Assessing the prognosis of acute myocardial infarction; Or (d) assessing the prognosis of cardiovascular diseases other than acute myocardial infarction that are associated with cardiac fibrosis. In one embodiment of the invention, the cardiac fibrosis comprises cardiac fibrosis caused by pressure loading and/or cardiac fibrosis caused by myocardial infarction. In one embodiment of the invention, the pressure load comprises aortic stenosis and/or hypertension. In one embodiment of the invention, the myocardial infarction comprises an acute myocardial infarction. In one embodiment of the invention, the cardiovascular disease associated with cardiac fibrosis other than acute myocardial infarction includes hypertension, diastolic heart failure, cardiomyopathy and/or sudden cardiac death. In one embodiment of the invention, diagnosing cardiac fibrosis includes determining whether the patient has cardiac fibrosis based on the concentration of hepatocyte growth factor in the plasma, determining that the patient has cardiac fibrosis if the concentration of hepatocyte growth factor in the plasma of the patient is significantly higher than in a normal population, and determining that the patient has no cardiac fibrosis if the concentration of hepatocyte growth factor in the plasma of the patient is close to that in a normal population. In one embodiment of the invention, the