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

Abstract

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.

HMGB2 Release Promotes Pulmonary Hypertension and Predicts Severity and Mortality of Patients With Pulmonary Arterial Hypertension

“…32 Thus, other circulating proteins originating from injured pulmonary vasculature may be more sensitive to early vascular pathology and useful in PH risk prediction. Consistent with the results of other studies, we previously found that serum HMGB2 was associated with in-stent restenosis and subclinical hypertension, 6,19 implying a role for serum HMGB2 in vascular pathological processes. The current study showed that HMGB2 expression was significantly increased in PAs, particularly in the smooth muscle layer in patients with PAH and in animal models.…”

“…6 Moreover, high HMGB2 serum levels correlated with hypertension and end-organ damage in young adults. 19 The pathogenic features of PH are similar to hallmark characteristics of cancer, including excessive proliferation, apoptosis resistance, and metabolic change to glycolysis (Warburg effect). 20 Under the condition of chronic hypoxia and monocrotaline (MCT) treatment, HMGB1 levels are elevated in lung tissue and blood plasma and the increased HMGB1 level contributes to the development of PH in animal models.…”

Quantitative Proteomics Provided Insights into the Protective Effects of Heat Acclimation on the Rat Hypothalamus after Exertional Heatstroke

“…Additionally, as an immunomodulatory molecule, ASS1 modulates the immunological microenvironment and cytokine response via C-X-C motif chemokine ligand 8 (CXCL8) signaling [55]. HMGB2 is known for its proinflammatory role in mobilizing innate immunity and is involved in signaling pathways that are associated with various inflammatory disorders [56]. VIM is critical for nucleotide-binding oligomer-ization domain (NOD)-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation, and its loss leads to decreased levels of proinflammatory cytokines, subsequently protecting against harmful inflammation [57].…”

Risk factors and a predictive model for left ventricular hypertrophy in young adults with salt‐sensitive hypertension

“…To ensure accuracy, we aimed to have at least 10 outcome events per variable (EPV) 32 . Considering the documented prevalence of LVH in the general population, 12,13 particularly the incidence of 20.4% in our center, 33 we anticipated a 25% event rate for LVH in our research. To include 10 or fewer predictors in the final multivariable logistic regression model, we estimated that a sample size of 400 patients or more would be required.…”