UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER AT DALLAS
Elevations in the circulating level of C-reactive protein (CRP) are a strong predictor of the development of
hypertension and insulin resistance. The proposed research program will determine how CRP and its cell
surface receptors cause hypertension and insulin resistance.
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| AWARD OVERVIEW |
| Award Number |
2R01HL075473-05A1 |
Funding Agency |
Department of Health and Human Services |
| Total Award Amount |
$1,087,420 |
Project Location - City |
Dallas |
| Award Date |
08/31/2009 |
Project Location - State |
TX |
| Project Status |
Completed |
Project Location - Zip |
75390-9020
|
| Jobs Reported |
0.00 |
Congressional District |
30 |
| Project Location - Country |
US |
|
|
Recipient Information
(Grants)
| Recipient Information (Grants) |
|
Recipient Name
|
UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER AT DALLAS |
| Recipient DUNS Number |
800771545
|
| Recipient Address |
5323 HARRY HINES BLVD |
| Recipient City |
DALLAS |
| Recipient State |
Texas |
| Recipient Zip |
75390-7208 |
| Recipient Congressional District |
30 |
| Recipient Country |
USA |
Required to Report Top 5
Highly Compensated Officials |
No |
Projects and Jobs Information
| Projects and Jobs Information |
| Project Title |
CRP, eNOS and Endothelial Dysfunction - ARRA Stimulus 2 Yr Resub |
| Project Status |
Completed |
| Final Project Report Submitted |
Yes |
| Project Activities Description |
Medical Specialties Research |
| Quarterly Activities/Project Description |
Total Expenditure Amount is less than the Award Amount. No more funds will be expended.The circulating level of Creactive protein(CRP)is a predictor of endothelial dysfunction&hypertension.In CRPtransgenic mice(TG-CRP),we showed CRP attenuates endothelial NO synthase(eNOS)function leading to hypertension,&CRP causes insulin resistance.We have evidence of endothelial cell expression of Fc?×RIIB.The PURPOSE is to test the hypothesis CRP actions via inhibitory IgG Fc?× receptor(Fc?×R)Fc?×RIIB in endothelial cells cause hypertension&insulin resistance.Our studies demonstrated TG-CRP mice are protected if null for Fc?×RIIB.Completed experiments found Fc?×RIIB-/-;TG-CRP mice are protected from insulin resistance.We discovered TG-CRP mice have blunted skeletal muscle glucose uptake associated with an attenuated skeletal muscle blood flow response to insulin.In contrast,uptake is normal in Fc?×RIIB-/-;TG-CRP mice who display normal insulin sensitivity.Studies in cell culture indicate that CRP completely prevents insulin uptake by endothelial cells,which is the ratelimiting step in insulin-induced skeletal muscle glucose uptake.We show that CRP administration to wildtype mice causes insulin resistance related to impaired skeletal muscle glucose uptake,and eNOS knockin mice expressing a constitutively-active mutant form of eNOS that cannot be inhibited by CRP are protected from these processes.Observations provide evidence that CRPinduced insulin resistance is a vascular phenotype.To delete Fc?×RIIB selectively from endothelium,we generated floxed Fc?×RIIB mice(Fc?×RIIBflox/flox),we demonstrated they have normal receptor expression and function,and we confirmed that the floxed gene is deleted by Cre-recombinase in vivo.We crossed Fc?×RIIBflox/flox mice with mice expressing Cre recombinase in endothelium,&confirmed gene excision in endothelium.Final experiments are testing if endothelial deletion of Fc?×RIIB provides protection from CRPinduced hypertension&insulin resistance. |
| Jobs Created |
0.00 |
| Description of Jobs Created |
N/A |
Purchaser Information
(Grants)
| Purchaser Information |
| Contracting Office ID |
Not Reported |
| Contracting Office Name |
Not Available |
| Contracting Office Region |
Not Available |
| TAS Major Program |
75-0871 |
| Award Information |
| Award Date |
08/31/2009 |
| Award Number |
2R01HL075473-05A1 |
| Order Number |
|
| Award Type |
Grants |
| Funding Agency ID |
75 |
| Funding Agency Name |
Department of Health and Human Services |
| Funding Office Name |
Not Available |
| Awarding Agency ID |
75 |
| Awarding Agency Name |
Department of Health and Human Services |
| Amount of Award |
$1,087,420 |
| Funds Invoiced/Received |
$1,087,317 |
| Expenditure Amount |
$1,087,317 |
| Infrastructure Expenditure Amount |
$0 |
| Infrastructure Purpose and Rationale |
Not Reported |
| Infrastructure Point of Contact Name |
Not Reported |
| Infrastructure Point of Contact Email |
Not Reported |
| Infrastructure Point of Contact Phone |
Not Reported |
| Infrastructure Point of Contact Address |
Not Reported |
| Infrastructure Point of Contact City |
Not Reported |
| Infrastructure Point of Contact State |
Not Reported |
| Infrastructure Point of Contact Zip |
Not Reported |
Product or Service Information
(Grants)
| Product or Service Information |
| Primary Activity Code |
H03.07 |
| Activity Description |
Medical Specialties Research |
| Sub-Awards Information |
| Sub-awards to Organizations |
0 |
| Sub-award Amounts to Organizations |
$0 |
| Sub-Awards to Individuals |
0 |
| Sub-Award Amounts to Individuals |
$0 |
| Number of Sub-awards less than $25,000/award |
0 |
| Amount of Sub-awards less than $25,000/award |
$0 |
| Number of payments to vendors greater than $25,000 |
0 |
| Total Amount of payments to vendors greater than $25,000/award |
$0 |
| Number of payments to vendors less than $25,000/award |
450 |
| Total Amount of payments to vendors less than $25,000/award |
$152,142 |
| Location Information |
| Latitude, Longitude |
32º 48' 45",
-96º 50' 18" |
| Congressional District |
30 |
| Address 1 |
5323 Harry Hines |
| Address 2 |
|
| City |
Dallas |
| County |
Dallas |
| State |
TX |
| Zip |
75390-9020 |
|
 |