Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 3 de 3
Filter
Add more filters










Database
Language
Publication year range
1.
Atherosclerosis ; 204(1): 79-84, 2009 May.
Article in English | MEDLINE | ID: mdl-18834983

ABSTRACT

OBJECTIVE: Despite the reciprocal relationship that exists between inflammation and thrombosis, we asked whether thrombosis can develop without inflammation, and whether stress-related hormones (ACTH and cortisol) influence platelet-mediated thrombosis. METHODS: We investigated the role of ACTH and cortisol in platelet aggregation, as well as on the circulating levels of IL-6 in pigs subjected to different treatments. In control animals, deep vessel wall injury (DVWI) was induced in the right common carotid artery, while in the animals under study DVWI was induced 60 min after ACTH administration (subgroup 1) or not at all (subgroup 2). In an ex vivo study we evaluated whether ACTH or cortisol modulates platelet aggregation. Indeed, we assessed whether blocking the P2Y platelet receptors inhibits the effect of ACTH on platelet aggregation. Finally, we assessed whether ACTH mobilizes intracellular calcium and modulates intracellular cAMP in platelets ex vivo. RESULTS: We found that the suppression of inflammation following ACTH administration was accompanied by acute arterial thrombosis in the zone of injury in vivo. Furthermore, ACTH but not cortisol amplifies the platelet aggregation induced ex vivo by agonists. Platelets do not express ACTH receptors which may explain why ACTH does not reduce intracellular levels of cAMP in platelets. Nevertheless, supraphysiological concentrations of ACTH increase calcium mobilization in platelets. CONCLUSION: These results indicate for the first time that ACTH may fulfil an important role in acute arterial thrombosis by increasing the platelet aggregation induced by agonists, probably via a G(q)-coupled pathway.


Subject(s)
Adrenocorticotropic Hormone/blood , Blood Platelets/metabolism , Carotid Artery Injuries/complications , Hydrocortisone/blood , Inflammation/prevention & control , Platelet Aggregation , Thrombosis/etiology , Acute Disease , Adrenocorticotropic Hormone/administration & dosage , Animals , Blood Platelets/drug effects , Calcium/blood , Carotid Artery Injuries/blood , Carotid Artery Injuries/immunology , Cyclic AMP/blood , Disease Models, Animal , Inflammation/blood , Inflammation/etiology , Inflammation/immunology , Injections, Intramuscular , Interleukin-6/blood , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/pharmacology , Purinergic P2 Receptor Antagonists , Receptors, Purinergic P2/blood , Receptors, Purinergic P2Y2 , Swine , Thrombosis/blood , Thrombosis/immunology , Time Factors
3.
Atherosclerosis ; 191(2): 333-9, 2007 Apr.
Article in English | MEDLINE | ID: mdl-16806229

ABSTRACT

Atherosclerosis is an inflammatory disease, but the response of the endogenous anti-inflammatory system during this process has not been evaluated previously. Cortisol is the end product of this anti-inflammatory system, but is also able to activate cellular processes that induce atherogenesis; however, it is unknown whether atherogenesis occurs when circulating concentrations of endogenous cortisol are increased or when they are decreased. We have evaluated the counter-regulatory responses of cortisol and interleukin-1beta (IL-1beta) during the short- and long-term responses to vascular injury in rabbits fed a 2% cholesterol diet. In the short-term group (n=18), serum cortisol and IL-1beta concentrations were measured after 10, 20 and 30 days. Rabbits developed hypercholesterolemia and hypercortisolemia, with only modest increases in IL-1beta. Although inflammation was low-grade, atherogenesis took place, with subintimal lipid accumulation evident on day 30. In the second group (n=18), we evaluated variables after 40, 60 and 90 days. This group developed hypercholesterolemia, but serum cortisol concentrations were inappropriately normal, while IL-1beta concentrations were elevated 8.6-fold; advanced atherosclerotic plaques were evident on days 60 and 90. These results show that atherogenesis occurs when high endogenous cortisol levels are suppressing inflammation, and are consistent with a promotion of early atherogenesis by high cortisol concentrations.


Subject(s)
Aorta, Thoracic/pathology , Atherosclerosis/etiology , Hydrocortisone/blood , Hypercholesterolemia/complications , Interleukin-1beta/blood , Animals , Atherosclerosis/blood , Atherosclerosis/pathology , Cholesterol/blood , Cholesterol, Dietary , Circadian Rhythm , Disease Models, Animal , Foam Cells/pathology , Hypercholesterolemia/blood , Hypercholesterolemia/chemically induced , Hypercholesterolemia/pathology , Inflammation/blood , Inflammation/etiology , Rabbits , Time Factors
SELECTION OF CITATIONS
SEARCH DETAIL
...