Document Detail


Age-associated induction of cell membrane CD47 limits basal and temperature-induced changes in cutaneous blood flow.
MedLine Citation:
PMID:  23275312     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: We tested the hypothesis that the matricellular protein thrombospondin-1 (TSP1), through binding to and activation of the cell receptor CD47, inhibits basal and thermal-mediated cutaneous blood flow.
BACKGROUND: Abnormal and decreased cutaneous blood flow in response to temperature changes or vasoactive agents is a feature of cardiovascular disease and aging. The reasons for decreased cutaneous blood flow remain incompletely understood. Furthermore, a role for matricellular proteins in the regulation skin blood flow has never been proposed.
METHODS: C57BL/6 wild type, TSP1-null, and CD47-null 12- and 72-week-old male mice underwent analysis of skin blood flow (SkBF) via laser Doppler in response to thermal stress and vasoactive challenge.
RESULTS: Young and aged TSP1- and CD47-null mice displayed enhanced basal and thermal sensitive SkBF changes compared with age-matched wild type controls. Nitric oxide-mediated increases in SkBF were also greater in null mice. TSP1 and CD47 were expressed in skin from young wild type mice, and both were significantly upregulated in aged animals. Tissue 3',5'-cyclic guanosine monophosphate, a potent vasodilator, was greater in skin samples from null mice compared with wild type regardless of age. Finally, treating wild type animals with a CD47 monoclonal antibody that inhibits TSP1 activation of CD47 enhanced SkBF in both young and aged animals.
CONCLUSIONS: These results suggest that secreted TSP1, via its cognate receptor CD47, acutely modulates SkBF. These data further support therapeutically targeting CD47 to mitigate age-associated loss of SkBF and maximize wound healing.
Authors:
Natasha M Rogers; David D Roberts; Jeffrey S Isenberg
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Annals of surgery     Volume:  258     ISSN:  1528-1140     ISO Abbreviation:  Ann. Surg.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-06-11     Completed Date:  2013-08-27     Revised Date:  2014-04-09    
Medline Journal Info:
Nlm Unique ID:  0372354     Medline TA:  Ann Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  184-91     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Age Factors
Analysis of Variance
Animals
Antibodies, Monoclonal / pharmacology
Antigens, CD47 / metabolism*
Blood Pressure / physiology
Cell Membrane / metabolism
Cyclic GMP / metabolism
Laser-Doppler Flowmetry
Male
Mice
Mice, Inbred C57BL
Nitric Oxide / pharmacology
RNA, Messenger / metabolism
Real-Time Polymerase Chain Reaction
Signal Transduction
Skin / blood supply*,  metabolism*
Temperature
Thrombospondin 1 / metabolism*
Grant Support
ID/Acronym/Agency:
1P01HL103455-01/HL/NHLBI NIH HHS; 1R01HL108954-01/HL/NHLBI NIH HHS; R01 HL112914/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antigens, CD47; 0/RNA, Messenger; 0/Thrombospondin 1; 31C4KY9ESH/Nitric Oxide; H2D2X058MU/Cyclic GMP

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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