Document Detail

Mild hypercholesterolemia blunts the proinflammatory and prothrombotic effects of hypertension on the cerebral microcirculation.
MedLine Citation:
PMID:  23281427     Owner:  NLM     Status:  MEDLINE    
Although an increased leukocyte and platelet adhesion is observed in cerebral venules of mice with either hypertension (HTN) or hypercholesterolemia (HCh), it remains unclear whether the combination of HTN and HCh exerts a comparable effect on leukocyte and platelet recruitment in the cerebral microvasculature. Thus, we examined whether HCh alters platelet and leukocyte adhesion, and blood-brain barrier (BBB) permeability, in cerebral venules in two models of murine HTN: DOCA salt-induced and angiotensin II (Ang II) induced. In both models, the mice were placed on either a normal or cholesterol-enriched diet. An enhanced recruitment of adherent leukocytes and platelets in cerebral venules was noted in both HTN models in the absence of HCh, but not in its presence. The Ang II-induced increase in BBB permeability was attenuated by HCh as well. Both total and high-density lipoprotein (HDL) cholesterol levels were elevated in the HCh mice. The HTN-induced increase in leukocyte and platelet adhesion was attenuated in apolipoprotein A-I transgenic mice (ApoA1-Tg) and blunted in wild-type mice treated with the ApoA1 mimetic peptide, 4F. Our findings indicate that mild HCh significantly blunts the cerebral microvascular responses to HTN and that HDL may have a role in mediating this beneficial effect of HCh.
Stephen F Rodrigues; Shantel A Vital; D Neil Granger
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Publication Detail:
Type:  Journal Article     Date:  2013-01-02
Journal Detail:
Title:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  33     ISSN:  1559-7016     ISO Abbreviation:  J. Cereb. Blood Flow Metab.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-01     Completed Date:  2013-05-23     Revised Date:  2014-04-01    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  483-9     Citation Subset:  IM    
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MeSH Terms
Angiotensin II / pharmacology
Apolipoprotein A-I / genetics,  metabolism
Blood-Brain Barrier / metabolism*,  physiopathology
Cerebrovascular Circulation*
Disease Models, Animal
Hypercholesterolemia / genetics,  metabolism*,  physiopathology
Hypertension / genetics,  metabolism*,  physiopathology
Lipoproteins, HDL / genetics,  metabolism
Mice, Transgenic
Vasoconstrictor Agents / pharmacology
Venules / metabolism,  physiopathology
Grant Support
Reg. No./Substance:
0/APOA1 protein, human; 0/Apolipoprotein A-I; 0/Lipoproteins, HDL; 0/Vasoconstrictor Agents; 11128-99-7/Angiotensin II

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