High Mobility Group Box-1 Is Increased in Newly Diagnosed Essential Hypertensives and Correlates With Hypertension-Mediated Target Organ Damage

Abstract

Objective:Chronic immune-mediated inflammation is increasingly recognized as an important contributor to target organ damage (TOD) in essential hypertension (EH). High mobility group box-1 (HMGB1) is a damage-associated molecular pattern (DAMP) molecule which stimulates innate immunity, hence exerting significant proinflammatory properties including vascular inflammation and thrombosis. So far, no clinical data exist regarding the role of HMGB1 in EH and its association with vascular damage. Our objective was to measure HMGB1 levels in newly diagnosed, untreated patients with EH (UHTs) compared to normotensive controls (NTs) and correlate them with indices of macro- and microvascular dysfunction, which play a core role in the pathogenesis of TOD in EH.Design and method:HMGB1 was measured in serum with ELISA. Ambulatory and central blood pressure (BP) parameters, and pulse wave velocity (PWV), were measured by using the Mobil-O-Graph device. Skin microcirculation was assessed with Laser Speckle Contrast Imaging (LSCI) coupled with post-occlusive reactive hyperemia (PORH). Results are expressed as a percentage increase between peak and baseline perfusion (%), and the amplitude of PORH response defined as peak Cutaneous Vascular Conductance (CVC) minus baseline CVC. The CVC was calculated as the flux in each period divided by mean arterial pressure [(PUs)/mmHg].Results:We consecutively enrolled 55 UHTs and 25 NTs matched for age and sex. HMGB1 levels were significantly higher in UHTs compared to NTs. HMGB1 showed a significant positive association with measures of macrocirculation including 24 h central systolic (0.325, p < 0.01) and diastolic BP (0.371, p < 0.01), day central systolic (0.353, p < 0.01) and diastolic BP (0.402, p < 0.01), and 24 h PWV (0.224, p < 0.05) and day PWV (0.230, p < 0.05) in the total study population. In addition, HMGB1 presented a significant negative association with skin microvascular parameters including base to peak flux (-0.247, p < 0.05) and PORH amplitude (-0.225, p < 0.01).Conclusions:HMGB1 is significantly increased in UHTs compared to NTs and correlates with indices of macro- and microvascular damage. These results reinforce the concept that immune system activation contributes to hypertension-mediated TOD from the very early stages and point towards intense research in order to investigate novel potential therapeutic targets related to EH.

Association of the hemoglobin glycation index with cardiovascular and all-cause mortality in individuals with hypertension: findings from NHANES 1999–2018

“…This variability, affected by factors like red blood cell lifespan and glycation rate, can cause discrepancies in diabetes management when using HbA1c alone. The connection between HGI and hypertension may be due to factors such as insulin resistance, a key mechanism in hypertension ( 9 ); second, its correlation with inflammation levels ( 10 ), a significant promoter of hypertension ( 11 ); and third, its association with oxidative stress ( 7 ), another critical factor in the development of hypertension. The HGI, reflecting cumulative glycemic exposure, could enhance understanding of long-term metabolic health in hypertensive individuals and complement traditional cardiovascular risk factors.…”