A biomarker for the diagnosis of vascular injury

Abstract

This invention provides a biomarker for diagnosing vascular injury, belonging to the field of medical diagnostics and biomarker detection technology. The biomarker for diagnosing vascular injury described in this invention is fibrinogen-5 (FBLN5). This invention reveals the relationship between FBLN5 levels and vascular injury, and develops it into a novel molecular detection tool for early diagnosis and risk assessment, filling a gap in existing technologies and providing a new pathway for population screening, early warning, and risk prediction of vascular injury. Compared to traditional imaging tests (such as CAG and IVUS), the FBLN5 biomarker method is more suitable for non-invasive or minimally invasive diagnosis, reducing invasive harm to patients. This makes it suitable as an early biomarker for vascular injury, applicable to screening high-risk populations.

Description

Technical Field

[0001] This invention belongs to the field of medical diagnostics and biomarker detection technology, and in particular relates to a biomarker for the diagnosis of vascular injury. Background Technology

[0002] Vascular injury is a common pathological basis for many cardiovascular diseases, and the incidence of coronary heart disease, aneurysm, aortic dissection, and atherosclerosis caused by vascular injury is increasing year by year worldwide. Endothelial cells and smooth muscle cells in the vascular wall structure play a crucial role in maintaining vascular homeostasis. Once these cells are damaged, a series of pathological processes, including inflammatory responses, oxidative stress, and extracellular matrix remodeling, will be triggered, which can ultimately lead to organ failure.

[0003] Currently, clinical assessment of vascular injury mainly relies on imaging examinations (such as vascular ultrasound, CT angiography, and fundus examination) and indirect physiological function tests (such as flow-mediated vasodilation). However, these methods have significant limitations. Imaging examinations can only identify abnormalities when significant structural changes in blood vessels have already occurred (such as plaque formation or luminal stenosis), making early diagnosis difficult. Functional tests are complex to perform and have low repeatability, making them unsuitable for large-scale population screening or routine physical examinations.

[0004] In the field of molecular diagnostics, the search for circulating biomarkers that can sensitively and specifically reflect early vascular injury has become a current research hotspot. Currently explored biomarkers mainly fall into two categories: one is inflammatory markers, such as C-reactive protein and interleukin-6. Although these biomarkers are associated with vascular inflammation, their specificity is low, and any systemic inflammation can cause their levels to rise; the other is endothelial cell injury markers, such as von Willebrand factor, thrombomodulin, and E-selectin. These can reflect endothelial dysfunction to some extent, but their levels are easily affected by various non-vascular factors, and their sensitivity is limited in early or mild vascular injury. Therefore, there is still a lack of an ideal circulating biomarker that can identify early or subclinical vascular injury with high specificity and sensitivity, which severely limits early warning, risk stratification, and effective intervention for vascular injury-related diseases. Summary of the Invention

[0005] In view of this, the purpose of this invention is to provide a biomarker for the diagnosis of vascular injury. This invention enables early screening and risk assessment of vascular injury by detecting the expression level of FBLN5 in a patient's blood, thereby providing a new detection method for the early identification and population screening of vascular injury.

[0006] To achieve the above-mentioned objectives, the present invention provides the following technical solution: The present invention provides a biomarker for the diagnosis of vascular injury, wherein the biomarker is fibrin-5.

[0007] Preferably, a plasma biomarker concentration of ≥3600 pg / mL indicates a risk of vascular damage.

[0008] Preferably, a plasma marker concentration of ≥5600 pg / mL indicates that blood vessels have been damaged.

[0009] This invention provides a detection reagent for vascular injury, wherein the detection reagent is a reagent for detecting the marker.

[0010] The present invention provides a kit for diagnosing vascular injury, the kit comprising the aforementioned detection reagent.

[0011] The present invention also provides the application of the aforementioned detection reagent or the aforementioned kit in the preparation of diagnostic products for vascular injury.

[0012] This invention also provides the use of fibrin-5 in the preparation of products for predicting vascular injury.

[0013] Preferably, the vascular injury includes aortic dissection, arterial stenosis, and intramural hematoma of the aorta.

[0014] Preferably, the product includes a reagent kit.

[0015] Preferably, the application includes predicting the risk of vascular injury by detecting the protein content of fibrin-5 and comparing it with a preset threshold.

[0016] Compared with the prior art, the present invention has the following beneficial effects: (1) This invention uses fibrin-5 (FBLN5) as a biomarker for the early diagnosis of vascular injury, reveals the relationship between plasma FBLN5 level and vascular injury, and develops it into a new, non-invasive molecular detection tool for early diagnosis and risk assessment, filling the gap in existing technology and providing a new path for the early identification of vascular injury and population screening.

[0017] (2) High sensitivity and specificity: Compared with traditional imaging tests (such as CAG, IVUS), FBLN5's biological detection method is more suitable for non-invasive or minimally invasive diagnosis, reducing invasive harm to patients.

[0018] (3) Early detection capability: Changes in FBLN5 expression may occur earlier than visible structural lesions in blood vessels, making it a suitable early biomarker for vascular injury screening in high-risk populations. Attached Figure Description

[0019] Figure 1 The screening scheme and results for FBLN5; Figure 2 The content of FBLN5 in the plasma of patients with different diseases, among which This indicates a difference in plasma FBLN5 levels between diseased and healthy control groups. p <0.01, This indicates a difference in plasma FBLN5 levels between diseased and healthy control groups. p <0.001; Figure 3 The receiver operating characteristic (ROC) curve for FBLN5; Figure 4 This is a flowchart of the experiment. Detailed Implementation

[0020] This invention provides a biomarker for the diagnosis of vascular injury, wherein the biomarker is FBLN5.

[0021] In this invention, preferably, when the level of the biomarker in the plasma is ≥3600 pg / mL, it indicates that the patient corresponding to the plasma sample is at risk of vascular damage and further invasive examinations are required; when the level of the biomarker in the plasma is ≥5600 pg / mL, it indicates that vascular damage has occurred and hospitalization is required to investigate the cause and actively intervene.

[0022] This invention provides a detection reagent for vascular injury, wherein the detection reagent is a reagent for detecting the marker.

[0023] The present invention provides a kit for diagnosing vascular injury, the kit comprising the aforementioned detection reagent.

[0024] The present invention also provides the application of the aforementioned detection reagent or the aforementioned kit in the preparation of diagnostic products for vascular injury.

[0025] This invention also provides the use of fibrin-5 in the preparation of products for predicting vascular injury.

[0026] In this invention, the vascular injury includes aortic dissection, arterial stenosis, and intramural hematoma of the aorta.

[0027] In this invention, the product includes a reagent kit.

[0028] In this invention, the application includes predicting the risk of vascular injury by detecting the protein content of fibrin-5 and comparing it with a preset threshold.

[0029] In this invention, the object of detection is a mammal, preferably a human.

[0030] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0031] Example 1

[0032] Four tissue samples each of atherosclerotic plaque tissue (from Xuanwu Hospital, Capital Medical University) and normal renal arteries (from Peking University Third Hospital) were collected for protein chip analysis (purchased from Ribobio (Guangzhou) Biotechnology Co., Ltd., catalog number: AAH-BLG-100-4) to identify differentially expressed proteins. Proteins with reduced expression in atherosclerotic plaques were designated as Group 1. Groups 2, 3, and 4 were proteomics data from public databases. Group 2 represented differentially expressed proteins in early and progressive plaques, Group 3 in stable and unstable plaques, and Group 4 in plaques and surrounding normal tissues. The intersection of the results from Groups 1, 2, 3, and 4 was analyzed. The results are shown below. Figure 1 .

[0033] Depend on Figure 1 It was found that by taking the intersection of the results of Groups 1, 2, 3, and 4, the common intersection of the four groups was FBLN5, and FBLN5 expression was lower in plaques / progressive / unstable plaques. The reason for this may be that FBLN5 can be released into the blood in large quantities when there is vascular injury, thus causing FBLN5 to show an abnormally high expression trend in patients with vascular injury.

[0034] Example 2

[0035] This study explored the changes in FBLN5 expression levels in the circulation of patients with vascular diseases by detecting the expression levels of FBLN5 in the blood of healthy individuals and patients with vascular diseases. The specific procedure is detailed in [link to procedure]. Figure 4 .

[0036] Plasma samples were collected from patients with different cardiovascular diseases (18 cases of aortic dissection, 20 cases of arterial stenosis, and 6 cases of aortic wall hematoma) (samples from patients with aortic dissection and intramural hematoma were obtained from the First Affiliated Hospital of Zhejiang University School of Medicine, and samples from patients with arterial stenosis were obtained from Fuwai Hospital of Chinese Academy of Medical Sciences) for further validation. 52 healthy individuals (from Peking University Third Hospital) served as controls. The level of FBLN5 protein in human plasma was detected using ELISA. Intergroup differences were analyzed using the Kruskal-Waillis H test. Results are expressed as Mean ± SD and are shown in the table below. Figure 2 Plasma FBLN5 levels in all patients included in the study were analyzed using GraphPadPrism 8.0.1 software (Table 1), and receiver operating characteristic (ROC) curves were plotted. The results are shown in [Table 1]. Figure 3 .

[0037] Table 1. FBLN5 content in plasma of different patients

[0038] Depend on Figure 2 It can be seen that, compared with healthy individuals, patients with pre-existing cardiovascular disease (vascular damage) have elevated plasma FBLN5 protein levels. This indicates that FBLN5 can be released into the bloodstream upon vascular injury, specifically manifested as elevated plasma FBLN5 levels. Based on Table 1 and the ROC curve (…),… Figure 3 The classification performance index table revealed that when the plasma FBLN5 protein level was >3600 pg / mL, it suggested that the patient might have suffered vascular damage and further examination was needed. When the FBLN5 protein level was >5600 pg / mL, it indicated that vascular damage had already occurred.

[0039] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A biomarker for diagnosing vascular injury, characterized in that, The marker is fibrin-5.

2. The marker according to claim 1, characterized in that, A plasma biomarker concentration ≥3600 pg / mL indicates a risk of vascular damage.

3. The marker according to claim 1, characterized in that, When the level of a biomarker in plasma is ≥5600 pg / mL, it indicates that blood vessels have been damaged.

4. A reagent for detecting vascular injury, characterized in that, The detection reagent is the reagent used to detect the marker described in claim 1.

5. A reagent kit for diagnosing vascular injury, characterized in that, The kit includes the detection reagent as described in claim 4.

6. The use of the detection reagent of claim 4 or the kit of claim 5 in the preparation of diagnostic products for vascular injury.

7. Application of fibrin-5 in the preparation of products for predicting vascular injury.

8. The application according to claim 7, characterized in that, The vascular injuries include aortic dissection, arterial stenosis, and intramural hematoma of the aorta.

9. The application according to claim 7, characterized in that, The product includes a reagent kit.

10. The application according to claim 7, characterized in that, The application includes predicting the risk of vascular damage by detecting the protein content of fibrin-5 and comparing it with a preset threshold.

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