Abstract

The role of leukocyte inflammatory markers and toll like receptors (TLRs)2/4 in pathologies associated with elevated resting heart rate (RHR) levels in healthy obese (HO) individuals is not well elucidated. Herein, we investigated the relationship of RHR with expression of leukocyte-inflammatory markers and TLRs in HO individuals. 58-obese and 57-lean participants with no history of a major medical condition, were recruited in this study. In HO individuals, the elevated-RHR correlated positively with diastolic blood pressure, cholesterol, pro-inflammatory monocytes CD11b+CD11c+CD206− phenotype (r = 0.52, P = 0.0003) as well as with activated T cells CD8+HLA-DR+ phenotype (r = 0.27, P = 0.039). No association was found between RHR and the percentage of CD16+CD11b+ neutrophils. Interestingly, elevated RHR positively correlated with cells expressing TLR4 and TLR2 (CD14+TLR4+, r = 0.51, P ≤ 0.0001; and CD14+TLR2+, r = 0.42, P = 0.001). TLR4+ expressing cells also associated positively with the plasma concentrations of proinflammatory or vascular permeability/matrix modulatory markers including TNF-α (r = 0.36, P = 0.005), VEGF (r = 0.47, P = 0.0002), and MMP-9 (r = 0.53, P ≤ 0.0001). Multiple regression revealed that RHR is independently associated with CD14+TLR4+ monocytes and VEGF. We conclude that in HO individuals, increased CD14+TLR4+ monocytes and circulatory VEGF levels associated independently with RHR, implying that RHR monitoring could be used as a non-invasive clinical indicator to identify healthy obese individuals at an increased risk of developing inflammation and cardiovascular disease.

Highlights

  • The role of leukocyte inflammatory markers and toll like receptors (TLRs)2/4 in pathologies associated with elevated resting heart rate (RHR) levels in healthy obese (HO) individuals is not well elucidated

  • Because changes in the expression of inflammatory leukocyte markers including TLRs were observed in obesity, we investigated the relationship of RHR with the expression of the leukocyte inflammatory markers and toll-like receptors (TLRs) 2/4 in healthy obese individuals

  • Our results show that in healthy obese individuals, increased C­ D14+TLR4+ monocytes and circulatory VEGF levels associated independently with RHR, suggesting that RHR monitoring could be used as a non-invasive clinical indicator to identify healthy obese individuals at risk for inflammation and cardiovascular disease (Fig. 4)

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Summary

Introduction

The role of leukocyte inflammatory markers and toll like receptors (TLRs)2/4 in pathologies associated with elevated resting heart rate (RHR) levels in healthy obese (HO) individuals is not well elucidated. The pathophysiology of chronic low-grade inflammation in obesity setting is associated with perturbation in the expression of leukocyte inflammatory markers and toll-like receptors (TLRs) 2/4 along with increased levels of MMP9, VEGF and cytokines such as tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6)[5,6,7]. Lower heart rates may benefit conditions, such as congestive heart failure, myocardial infarction, atrial fibrillation, obesity, hyperinsulinemia, insulin resistance, and atherosclerosis Given these studies, it may be speculated that obese individuals are at a risk of RHR modulation from obesity-associated changes in the autonomic nerve function. Our multiple regression analysis showed that RHR is independently associated with ­CD14+TLR4+ monocytes and VEGF expression

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