Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

SEROTONIN 5-HT2A RECEPTOR INHIBITION OF TNF-ALPHA PATHWAYS AND ATHEROSCLEROSIS

Award Number: R21HL095961
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/15/2010
PERIOD OF PERFORMANCE END DATE: 12/31/2013

Group Awards By:

View Award Description

SEROTONIN 5-HT2A RECEPTOR INHIBITION OF TNF-ALPHA PATHWAYS AND ATHEROSCLEROSIS - DESCRIPTION (provided by applicant): The overall goals of this project are to elucidate the molecular mechanisms underlying our recent discovery that serotonin 5-HT2A receptor activation super-potently inhibits TNFa-mediated inflammatory pathways, and to translate our findings to an animal model as a potential novel therapeutic approach to treat and/or prevent diseases like atherosclerosis that involve TNFa-mediated inflammation. TNF- a-mediated inflammatory pathways have been strongly implicated in a number of diseases including atherosclerosis, rheumatoid arthritis, psoriasis, type II diabetes, irritable bowel syndrome and Crohn's disease, and septicemia. Significantly, TNF-a and other cytokine induced inflammatory pathways also have been linked to psychiatric conditions such as depression and bipolar disorder, as well as schizophrenia, and neurodegenerative diseases. As such, inhibitors of TNF-a pro-inflammatory pathways represent potential therapeutics for each of these conditions. Currently, the only available therapeutic inhibitors of TNF-a pathways are monoclonal antibodies against TNF-a (infliximab and adalimumab) and soluble TNF-a receptor (etanercept), and the development of small molecules for this purpose is highly desirable. We have recently discovered that activation of 5-HT2A receptors in cardiovascular tissues including primary aortic smooth muscle, aortic endothelial, and macrophage cells by (R)-DOI, and likely additional 5-HT2A receptor agonists, represents a novel, and extraordinarily potent, therapeutic avenue to develop for the treatment of diseases and disorders involving TNF-a-mediated inflammation. Significantly, pro-inflammatory marker blockade occurs with IC50 drug levels of 10-20 picomolar. With the exception of a few natural toxins no current drugs or small molecule therapeutics demonstrate a comparable potency for any physiological effect. The experiments described in this proposal will elucidate the molecular signaling pathways linking activation of 5-HT2A receptors to inhibition of TNF- a-mediated pro-inflammatory process using molecular and biochemical approaches in primary cell culture experiments. Importantly, we will also perform translational studies in rodents to explore the anti-inflammatory effects of (R)-DOI in vivo. Results from these studies may lead to potential therapeutic strategies to not only prevent, but also treat existing pathological conditions like atherosclerosis via 5-HT2A receptor stimulation.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2013 ( Subtotal = $0 )
2013	2011	LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER	433 BOLIVAR STREET	NEW ORLEANS	LA	70112	ORLEANS	USA	Cardiovascular Diseases Research	000	2	7/2/2013	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2011 ( Subtotal = $177,500 )
2011	2011	LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER	433 BOLIVAR STREET	NEW ORLEANS	LA	70112	ORLEANS	USA	Cardiovascular Diseases Research	000	2	6/17/2011	NON-COMPETING CONTINUATION	$177,500
														Subtotal = $177,500

Issue Date FY: 2010 ( Subtotal = $213,000 )
2010	2010	LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER	433 BOLIVAR STREET	NEW ORLEANS	LA	70112	ORLEANS	USA	Cardiovascular Diseases Research	000	1	7/9/2010	NEW	$213,000
														Subtotal = $213,000

Grand Total All Awards = $390,500

Top

All Categories

About

Search

Reports

Data Submission

Award Information

SEROTONIN 5-HT2A RECEPTOR INHIBITION OF TNF-ALPHA PATHWAYS AND ATHEROSCLEROSIS

Award Number: R21HL095961

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/15/2010

PERIOD OF PERFORMANCE END DATE: 12/31/2013

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer