Beta-adrenergic receptor mediated inflammation control by monocytes is associated with blood pressure and risk factors for cardiovascular disease

Suzi Hong, Stoyan Dimitrov, Tiefu Cheng, Laura Redwine, Christopher Pruitt, Paul J Mills, Michael G Ziegler, J Michael Green, Farah Shaikh, Kathleen Wilson, Suzi Hong, Stoyan Dimitrov, Tiefu Cheng, Laura Redwine, Christopher Pruitt, Paul J Mills, Michael G Ziegler, J Michael Green, Farah Shaikh, Kathleen Wilson

Abstract

Overwhelming data indicate that individuals with even mildly elevated blood pressure (BP) are at great risk for developing clinical hypertension and future cardiovascular disease (CVD). There remains a lack of consensus regarding treatment strategies for mildly elevated BP, termed prehypertension, and the knowledge of pathophysiology and mechanisms of its clinical outcomes remains limited. Our primary aim was to investigate βAR-mediated inflammation control (BARIC) responses of blood monocytes to isoproterenol (Iso) in relation to BP and CVD risk factors, including obesity, depressive mood, fasting glucose, triglycerides, and cholesterol levels in the 64 prehypertensive compared to 84 individuals with normal BP. BARIC was determined by measuring the degree of inhibition in lipopolysaccharides-stimulated monocytic intracellular TNF production by ex vivo Iso treatment (10(-8)M). Depressive mood was assessed by Beck Depression Inventory (BDI). Fasting metabolic and lipid panels were assessed, and plasma levels of inflammatory cytokines TNF, IL-1β, IL-6 were measured in a subset to confirm proinflammatory state of prehypertensive participants. Prehypertensive participants were older, heavier, included more men, and presented higher levels of fasting glucose, triglycerides, cholesterol, and plasma TNF compared to normotensive participants (p's<.05). BARIC was significantly attenuated in the prehypertensive compared to normotensive group (p<.05). BARIC was negatively associated with systolic BP, diastolic BP, age, BMI, fasting glucose, triglycerides, total and low density cholesterol levels, and somatic depressive symptoms in all participants (p's<.0001 to .05). However, among the prehypertensive individuals BARIC was positively associated with SBP even after controlling for the covariates (age, gender, race, BMI, glucose and lipid panel, somatic BDI scores) (p<.05). This differing nature of the BARIC-SBP relationship between the two BP groups may be attributed to moderating factors such as cardiorespiratory fitness or depressive symptoms that could not be clearly deciphered in this current study. Nonetheless, our findings indicate the associations between inflammation dysregulation mediated by sympathoadrenal activation and BP that is observable even among individuals with normal to mildly elevated BP. BARIC may be a useful and sensitive indicator of elevated risk for vascular inflammatory disease that can be detected even at lower BP levels, especially given its associations with traditional CVD risk factors and the critical role of monocytes in atherogenic processes.

Keywords: Beta adrenergic receptor; Blood pressure; Depression; Fasting glucose; Intracellular TNF levels; Lipids; Monocytes; Prehypertension.

Conflict of interest statement

Conflict of Interest Statement: All authors declare that there are no conflicts of interest.

Copyright © 2015 Elsevier Inc. All rights reserved.

Figures

Figure 1
Figure 1
Beta AR-mediated inflammation control (BARIC), assessed by the degree of the inhibition of monocytic TNF production by 10−8, 10−9, or 10−10 M Iso in the normotensive (NTN) vs. prehypertensive (PHT) BP groups. BARIC of two BP groups for all three Iso concentrations are depicted to showcase the reliability of the group difference and internal validity. Values are presented as mean ± SEM. Overall between group differences were significant for all Iso concentrations (p’s< 0.05).
Figure 2
Figure 2
Beta AR-mediated inflammation control (BARIC) at Iso 10−8 was positively correlated with both SBP (r=−.23, p< .01) and DBP (r= −.28, p= .001). The normotensive (NTN) group showed similar associations with smaller effect sizes (r= −.20, p= .07 for SBP; r= −.17, p= .13 for DBP) when analyzed separately. However, BARIC was positively associated with SBP (r= .18, p= .16) in prehypertensive (PHT) participants in spite of the negative correlation between BARIC and DBP (r= −.23, p= .07). Although none of the correlations were significant at p< .05 level, multivariate regression analyses confirmed that BARIC was independently predictive of SBP among prehypertensive participants after controlling for the covariates (p< .05). Scatter plots are presented using raw (pre-transform) SBP values for immediately interpretable illustration, although the analyses were done in log-transformed SBP values.

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