Association between high-mobility group box 2 and subclinical hypertension-mediated organ damage in young adults

Background: Hypertension-mediated organ damage (HMOD) is an emerging problem among young adults. The potential role of chronic immune-mediated inflammation in the pathogenesis of HMOD is increasingly being recognized. High-mobility group box 2 (HMGB2) is known for its role in the modulation of innat...

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Main Authors: Jindong Wan, Gang Liu, Siwei Xia, Sen Liu, Yi Yang, Dan Wang, Jixin Hou, Xiaozhen Dai, Peng Zhou, Peijian Wang
Format: Article
Language:English
Published: SAGE Publishing 2022-11-01
Series:Therapeutic Advances in Chronic Disease
Online Access:https://doi.org/10.1177/20406223221135011
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author Jindong Wan
Gang Liu
Siwei Xia
Sen Liu
Yi Yang
Dan Wang
Jixin Hou
Xiaozhen Dai
Peng Zhou
Peijian Wang
author_facet Jindong Wan
Gang Liu
Siwei Xia
Sen Liu
Yi Yang
Dan Wang
Jixin Hou
Xiaozhen Dai
Peng Zhou
Peijian Wang
author_sort Jindong Wan
collection DOAJ
description Background: Hypertension-mediated organ damage (HMOD) is an emerging problem among young adults. The potential role of chronic immune-mediated inflammation in the pathogenesis of HMOD is increasingly being recognized. High-mobility group box 2 (HMGB2) is known for its role in the modulation of innate immunity and exerts signaling functions that affect various inflammatory diseases. However, the association between HMGB2 and HMOD in young adults remains unclear. Objectives: The aim of this study was to explore the association between HMGB2 and subclinical HMOD in young adults. Design: This is a cross-sectional study. Methods: Body composition, carotid ultrasound, carotid-femoral PWV (cf-PWV) measures, echocardiography, serum HMGB2 levels, and serum classic cardiometabolic risk factors were measured in 988 untreated young adults. We estimated the risk related to serum HMGB2 using multivariable-adjusted linear and logistic regression models. Then, we conducted a pathway overrepresentation analysis to examine which key biological pathways may be linked to serum HMGB2 in young adults with HMOD. Results: Among the 988 untreated young adults, we identified four distinct hypertension phenotypes: normotension (40.0%), white-coat hypertension (16.0%), masked hypertension (20.9%), and sustained hypertension (23.1%). High levels of serum HMGB2 were related to increased carotid intima-media thickness (cIMT) and left ventricular mass index (LVMI), higher cf-PWV and blood pressure, and a lower estimated glomerular filtration rate (eGFR). Linear regression analysis showed that serum HMGB2 was positively associated with cf-PWV and negatively associated with eGFR in all patients. Multivariate analysis showed that high levels of serum HMGB2 were associated with high odds of subclinical HMOD (damage in at least one organ). Biological pathway analysis indicated that patients with high serum HMGB2 levels had increased activity of pathways, related to endothelial dysfunction, inflammatory processes, and atherosclerosis. Conclusion: High serum concentrations of HMGB2 are associated with an increased risk of subclinical HMOD in untreated young adults.
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spelling doaj.art-de415651d3ee45449647c00eaa1b436d2022-12-22T04:38:53ZengSAGE PublishingTherapeutic Advances in Chronic Disease2040-62312022-11-011310.1177/20406223221135011Association between high-mobility group box 2 and subclinical hypertension-mediated organ damage in young adultsJindong WanGang LiuSiwei XiaSen LiuYi YangDan WangJixin HouXiaozhen DaiPeng ZhouPeijian WangBackground: Hypertension-mediated organ damage (HMOD) is an emerging problem among young adults. The potential role of chronic immune-mediated inflammation in the pathogenesis of HMOD is increasingly being recognized. High-mobility group box 2 (HMGB2) is known for its role in the modulation of innate immunity and exerts signaling functions that affect various inflammatory diseases. However, the association between HMGB2 and HMOD in young adults remains unclear. Objectives: The aim of this study was to explore the association between HMGB2 and subclinical HMOD in young adults. Design: This is a cross-sectional study. Methods: Body composition, carotid ultrasound, carotid-femoral PWV (cf-PWV) measures, echocardiography, serum HMGB2 levels, and serum classic cardiometabolic risk factors were measured in 988 untreated young adults. We estimated the risk related to serum HMGB2 using multivariable-adjusted linear and logistic regression models. Then, we conducted a pathway overrepresentation analysis to examine which key biological pathways may be linked to serum HMGB2 in young adults with HMOD. Results: Among the 988 untreated young adults, we identified four distinct hypertension phenotypes: normotension (40.0%), white-coat hypertension (16.0%), masked hypertension (20.9%), and sustained hypertension (23.1%). High levels of serum HMGB2 were related to increased carotid intima-media thickness (cIMT) and left ventricular mass index (LVMI), higher cf-PWV and blood pressure, and a lower estimated glomerular filtration rate (eGFR). Linear regression analysis showed that serum HMGB2 was positively associated with cf-PWV and negatively associated with eGFR in all patients. Multivariate analysis showed that high levels of serum HMGB2 were associated with high odds of subclinical HMOD (damage in at least one organ). Biological pathway analysis indicated that patients with high serum HMGB2 levels had increased activity of pathways, related to endothelial dysfunction, inflammatory processes, and atherosclerosis. Conclusion: High serum concentrations of HMGB2 are associated with an increased risk of subclinical HMOD in untreated young adults.https://doi.org/10.1177/20406223221135011
spellingShingle Jindong Wan
Gang Liu
Siwei Xia
Sen Liu
Yi Yang
Dan Wang
Jixin Hou
Xiaozhen Dai
Peng Zhou
Peijian Wang
Association between high-mobility group box 2 and subclinical hypertension-mediated organ damage in young adults
Therapeutic Advances in Chronic Disease
title Association between high-mobility group box 2 and subclinical hypertension-mediated organ damage in young adults
title_full Association between high-mobility group box 2 and subclinical hypertension-mediated organ damage in young adults
title_fullStr Association between high-mobility group box 2 and subclinical hypertension-mediated organ damage in young adults
title_full_unstemmed Association between high-mobility group box 2 and subclinical hypertension-mediated organ damage in young adults
title_short Association between high-mobility group box 2 and subclinical hypertension-mediated organ damage in young adults
title_sort association between high mobility group box 2 and subclinical hypertension mediated organ damage in young adults
url https://doi.org/10.1177/20406223221135011
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