title: Beta-adrenergic receptor mediated inflammation control by monocytes is associated with blood pressure and risk factors for cardiovascular disease.
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.
authors: Department of Psychiatry, University of California San Diego, USA; Department of Family Medicine and Public Health, University of California San Diego, USA. Electronic address: suzihong@ucsd.edu.
authors: Suzi
authors: S
authors: Hong
authors: Department of Psychiatry, University of California San Diego, USA.
authors: Stoyan
authors: S
authors: Dimitrov
authors: Department of Psychiatry, University of California San Diego, USA.
authors: Tiefu
authors: T
authors: Cheng
authors: Department of Psychiatry, University of California San Diego, USA.
authors: Laura
authors: L
authors: Redwine
authors: Department of Psychiatry, University of California San Diego, USA.
authors: Christopher
authors: C
authors: Pruitt
authors: Department of Psychiatry, University of California San Diego, USA; Department of Family Medicine and Public Health, University of California San Diego, USA.
authors: Paul J
authors: PJ
authors: Mills
authors: Department of Medicine, University of California San Diego, USA.
authors: Michael G
authors: MG
authors: Ziegler
authors: Department of Psychiatry, University of California San Diego, USA.
authors: J Michael
authors: JM
authors: Green
authors: Department of Psychiatry, University of California San Diego, USA.
authors: Farah
authors: F
authors: Shaikh
authors: Department of Psychiatry, University of California San Diego, USA.
authors: Kathleen
authors: K
authors: Wilson
mesh_terms: D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D002784:Cholesterol / Q000097:blood; D003863:Depression / Q000150:complications; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: D000318:Adrenergic beta-Agonists; D001786:Blood Glucose; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D011943:Receptors, Adrenergic, beta; D014409:Tumor Necrosis Factor-alpha; D002784:Cholesterol; D007545:Isoproterenol
keywords: Beta adrenergic receptor; Blood pressure; Depression; Fasting glucose; Intracellular TNF levels; Lipids; Monocytes; Prehypertension