Prediction of herbal medicines based on immune cell infiltration and immune- and ferroptosis-related gene expression levels to treat valvular atrial fibrillation
Inflammatory immune response is apparently one of the determinants of progressive exacerbation of valvular atrial fibrillation(VAF). Ferroptosis, an iron-dependent modality of regulated cell death, is involved in the immune regulation of cardiovascular disease. However, the relevant regulatory mecha...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-09-01
|
| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.886860/full |
| _version_ | 1811265601346207744 |
|---|---|
| author | Feng Jiang Weiwei Zhang Hongdan Lu Meiling Tan Zhicong Zeng Yinzhi Song Xiao Ke Fengxia Lin |
| author_facet | Feng Jiang Weiwei Zhang Hongdan Lu Meiling Tan Zhicong Zeng Yinzhi Song Xiao Ke Fengxia Lin |
| author_sort | Feng Jiang |
| collection | DOAJ |
| description | Inflammatory immune response is apparently one of the determinants of progressive exacerbation of valvular atrial fibrillation(VAF). Ferroptosis, an iron-dependent modality of regulated cell death, is involved in the immune regulation of cardiovascular disease. However, the relevant regulatory mechanisms of immune infiltration and ferroptosis in VAF have been less studied. In the current study, a highly efficient system for screening immunity- and ferroptosis-related biomarkers and immunomodulatory ability of herbal ingredients has been developed with the integration of intelligent data acquisition, data mining, network pharmacology, and computer-assisted target fishing. VAF patients showed higher infiltration of neutrophils and resting stage dendritic cells, while VSR patients showed higher infiltration of follicular helper T cells. In addition, six (e.g., PCSK2) and 47 (e.g., TGFBR1) ImmDEGs and one (SLC38A1) and four (TGFBR1, HMGB1, CAV1, and CD44) FerDEGs were highly expressed in patients with valvular sinus rhythm (VSR) and VAF, respectively. We further identified a core subnetwork containing 34 hub genes, which were intersected with ImmDEGs and FerDEGs to obtain the key gene TGFBR1. Based on TGFBR1, 14 herbs (e.g., Fructus zizyphi jujubae, Semen Juglandis, and Polygonum cuspidatum) and six herbal ingredients (curcumin, curcumine, D-glucose, hexose, oleovitamin A, and resveratrol) were predicted. Finally, TGFBR1 was found to dock well with curcumin and resveratrol, and it was further verified that curcumin and resveratrol could significantly reduce myocardial fibrosis. We believe that herbs rich in curcumin and resveratrol such as Rhizoma curcumae longae and Curcuma kwangsiensis, mitigate myocardial fibrosis to improve VAF by modulating the TGFβ/Smad signaling pathway. This strategy provides a prospective approach systemically characterizing phenotype-target-herbs relationships based on the tissue-specific biological functions in VAF and brings us new insights into the searching lead compounds from Chinese herbs. |
| first_indexed | 2024-04-12T20:26:47Z |
| format | Article |
| id | doaj.art-122040078aa84a788e907da23a825f4f |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-12T20:26:47Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-122040078aa84a788e907da23a825f4f2022-12-22T03:17:51ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-09-011310.3389/fgene.2022.886860886860Prediction of herbal medicines based on immune cell infiltration and immune- and ferroptosis-related gene expression levels to treat valvular atrial fibrillationFeng Jiang0Weiwei Zhang1Hongdan Lu2Meiling Tan3Zhicong Zeng4Yinzhi Song5Xiao Ke6Fengxia Lin7Cardiology Department, Affiliated Baoan TCM Hospital, Guangzhou University of Traditional Chinese Medicine, Shenzhen, ChinaCardiology Department, Affiliated Baoan TCM Hospital, Guangzhou University of Traditional Chinese Medicine, Shenzhen, ChinaCardiology Department, Affiliated Baoan TCM Hospital, Guangzhou University of Traditional Chinese Medicine, Shenzhen, ChinaWenhua Community Health Service Center, Shenzhen Luohu Hospital Group, Shenzhen, ChinaCardiology Department, Affiliated Baoan TCM Hospital, Guangzhou University of Traditional Chinese Medicine, Shenzhen, ChinaCardiology Department, Affiliated Baoan TCM Hospital, Guangzhou University of Traditional Chinese Medicine, Shenzhen, ChinaDepartment of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen(Shenzhen Sun Yat-sen Cardiovascular Hospital), Shenzhen, ChinaCardiology Department, Affiliated Baoan TCM Hospital, Guangzhou University of Traditional Chinese Medicine, Shenzhen, ChinaInflammatory immune response is apparently one of the determinants of progressive exacerbation of valvular atrial fibrillation(VAF). Ferroptosis, an iron-dependent modality of regulated cell death, is involved in the immune regulation of cardiovascular disease. However, the relevant regulatory mechanisms of immune infiltration and ferroptosis in VAF have been less studied. In the current study, a highly efficient system for screening immunity- and ferroptosis-related biomarkers and immunomodulatory ability of herbal ingredients has been developed with the integration of intelligent data acquisition, data mining, network pharmacology, and computer-assisted target fishing. VAF patients showed higher infiltration of neutrophils and resting stage dendritic cells, while VSR patients showed higher infiltration of follicular helper T cells. In addition, six (e.g., PCSK2) and 47 (e.g., TGFBR1) ImmDEGs and one (SLC38A1) and four (TGFBR1, HMGB1, CAV1, and CD44) FerDEGs were highly expressed in patients with valvular sinus rhythm (VSR) and VAF, respectively. We further identified a core subnetwork containing 34 hub genes, which were intersected with ImmDEGs and FerDEGs to obtain the key gene TGFBR1. Based on TGFBR1, 14 herbs (e.g., Fructus zizyphi jujubae, Semen Juglandis, and Polygonum cuspidatum) and six herbal ingredients (curcumin, curcumine, D-glucose, hexose, oleovitamin A, and resveratrol) were predicted. Finally, TGFBR1 was found to dock well with curcumin and resveratrol, and it was further verified that curcumin and resveratrol could significantly reduce myocardial fibrosis. We believe that herbs rich in curcumin and resveratrol such as Rhizoma curcumae longae and Curcuma kwangsiensis, mitigate myocardial fibrosis to improve VAF by modulating the TGFβ/Smad signaling pathway. This strategy provides a prospective approach systemically characterizing phenotype-target-herbs relationships based on the tissue-specific biological functions in VAF and brings us new insights into the searching lead compounds from Chinese herbs.https://www.frontiersin.org/articles/10.3389/fgene.2022.886860/fullimmune cell infiltrationferroptosisatrial fibrillationherbal medicineprediction |
| spellingShingle | Feng Jiang Weiwei Zhang Hongdan Lu Meiling Tan Zhicong Zeng Yinzhi Song Xiao Ke Fengxia Lin Prediction of herbal medicines based on immune cell infiltration and immune- and ferroptosis-related gene expression levels to treat valvular atrial fibrillation Frontiers in Genetics immune cell infiltration ferroptosis atrial fibrillation herbal medicine prediction |
| title | Prediction of herbal medicines based on immune cell infiltration and immune- and ferroptosis-related gene expression levels to treat valvular atrial fibrillation |
| title_full | Prediction of herbal medicines based on immune cell infiltration and immune- and ferroptosis-related gene expression levels to treat valvular atrial fibrillation |
| title_fullStr | Prediction of herbal medicines based on immune cell infiltration and immune- and ferroptosis-related gene expression levels to treat valvular atrial fibrillation |
| title_full_unstemmed | Prediction of herbal medicines based on immune cell infiltration and immune- and ferroptosis-related gene expression levels to treat valvular atrial fibrillation |
| title_short | Prediction of herbal medicines based on immune cell infiltration and immune- and ferroptosis-related gene expression levels to treat valvular atrial fibrillation |
| title_sort | prediction of herbal medicines based on immune cell infiltration and immune and ferroptosis related gene expression levels to treat valvular atrial fibrillation |
| topic | immune cell infiltration ferroptosis atrial fibrillation herbal medicine prediction |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.886860/full |
| work_keys_str_mv | AT fengjiang predictionofherbalmedicinesbasedonimmunecellinfiltrationandimmuneandferroptosisrelatedgeneexpressionlevelstotreatvalvularatrialfibrillation AT weiweizhang predictionofherbalmedicinesbasedonimmunecellinfiltrationandimmuneandferroptosisrelatedgeneexpressionlevelstotreatvalvularatrialfibrillation AT hongdanlu predictionofherbalmedicinesbasedonimmunecellinfiltrationandimmuneandferroptosisrelatedgeneexpressionlevelstotreatvalvularatrialfibrillation AT meilingtan predictionofherbalmedicinesbasedonimmunecellinfiltrationandimmuneandferroptosisrelatedgeneexpressionlevelstotreatvalvularatrialfibrillation AT zhicongzeng predictionofherbalmedicinesbasedonimmunecellinfiltrationandimmuneandferroptosisrelatedgeneexpressionlevelstotreatvalvularatrialfibrillation AT yinzhisong predictionofherbalmedicinesbasedonimmunecellinfiltrationandimmuneandferroptosisrelatedgeneexpressionlevelstotreatvalvularatrialfibrillation AT xiaoke predictionofherbalmedicinesbasedonimmunecellinfiltrationandimmuneandferroptosisrelatedgeneexpressionlevelstotreatvalvularatrialfibrillation AT fengxialin predictionofherbalmedicinesbasedonimmunecellinfiltrationandimmuneandferroptosisrelatedgeneexpressionlevelstotreatvalvularatrialfibrillation |