Catecholamines Can Attenuate Intermittent Hypoxia-Induced Expression of TNF in Human Monocytes

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2006 by National Taiwan University Hospital.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT00498862
First received: July 8, 2007
Last updated: July 9, 2007
Last verified: September 2006
  Purpose

Specific aim To examine the effect of catecholamines on the modulation of intermittent hypoxia induced TNF- in human monocytes from both healthy subjects and OSA patients (2). To map the signaling pathway of catecholamines regulating the intermittent hypoxia induced TNF- expression.

(3). To explore the potential therapeutic effects of  or  agonists/antagonists on intermittent hypoxia induced TNF- expression


Condition
Healthy

Study Type: Observational
Study Design: Observational Model: Defined Population
Time Perspective: Cross-Sectional

Further study details as provided by National Taiwan University Hospital:

Estimated Enrollment: 15
Study Start Date: September 2006
Detailed Description:

Obstructive sleep apnea syndrome (OSAS) is a common disease, which occurs in 4% middle-aged men and 2% middle-aged women. The characteristic of OSA is recurrent collapse of upper airway during sleep, which results in intermittent hypoxia and sympathetic activation. Cardiovascular complications associated with OSA include artherosclerosis, hypertension, coronary artery disease and congestive heart failure. Several inflammatory mediators including C-reactive protein (CRP), oxidative stress, adhesion molecules, vascular endothelial growth factor and proinflammatory cytokines, were found to be elevated in OSA, which attribute the developments of cardiovascular diseases in OSA. Our data showed serum levels of TNF were higher in OSA patients than in control subjects. And serum levels of TNF were inversely correlated with the lowest pulse oxygen saturation. After one-month CPAP treatment, serum of TNF could significantly go down. This finding suggested TNF was a good biomarker in studying OSA associated cardiovascular complications.

The presentations of sympathetic hyperactivity in OSA include hypercatecholaminemia and elevated sympathetic tone of peripheral nerve. Hypercatecholaminemia is known for attributing to the development of cardiovascular diseases. Our data showed plasma levels of both epinephrine and norepinephrine were higher in OSA patients than in control subjects. And the elevated catecholamine could go down after one-month CPAP treatment. Meanwhile, our data also showed the plasma levels of catecholamine were highly correlated with serum levels of TNF.

In vivo studies showed both epinephrine and norepinephrine could potentiate LPS-induced expression of TNF through 2 adrenergic receptors. However, the effect of catecholamine on TNF production in human monocytes in the hypoxic microenvironment has never been studied. Our preliminary data showed epinephrine had no effect on TNF expression in human monocyte cell line U937 under normoxic condition but could attenuate the TNF expression under hypoxic condition. Therefore, we hypothesize that catecholamines can modulate intermittent hypoxia induced TNF and further affect the developments of cardiovascular complications in OSA. In this project, we’ll use peripheral blood monocytes from healthy subjects and OSA patients as the target cells, which were serially treated with catecholamine  or b antagonists in both normoxic and hypoxic microenvironments, to achieve the following 3 objectives:

  1. . To examine the effect of catecholamines on the modulation of intermittent hypoxia induced TNF- in human monocytes from both healthy subjects and OSA patients
  2. . To map the signaling pathway of catecholamines regulating the intermittent hypoxia induced TNF- expression.
  3. . To explore the potential therapeutic effects of  or  agonists/antagonists on intermittent hypoxia induced TNF- expression
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy volunteer
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00498862

Contacts
Contact: Peilin Lee, M.D. +886-2-23562905 peilin1986@yahoo.com.tw

Locations
Taiwan
National Taiwan University Hospital Recruiting
Taipei, Taiwan, 100
Contact: Peilin Lee, M.D.    +882-2-23562905    peilin1986@yahoo.com.tw   
Sponsors and Collaborators
National Taiwan University Hospital
Investigators
Principal Investigator: Peiln Lee, M.D. National Taiwan Univerisity Hospital
Principal Investigator: Peilin Lee, M.D. National Taiwan University Hospital
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00498862     History of Changes
Other Study ID Numbers: 9561709069
Study First Received: July 8, 2007
Last Updated: July 9, 2007
Health Authority: Taiwan: Department of Health

ClinicalTrials.gov processed this record on August 01, 2014