Endothelium-derived Vasoactive Factors and Leukocyte-derived Inflammatory Mediators. Studies in subjects with or at risk for vascular disease

Research output: ThesisDoctoral Thesis (compilation)

Abstract

This study was undertaken to evaluate relationships between endothelial function (assessed as mediators of endothelium-derived vasoactive factors such as nitric oxide [NO], prostacyclin [PGI2] and endothelin [ET-1] ), and risk factors for atherosclerosis, as well as to study possible relationships between endothelial function and leukocyte activation (indicated by measurements of leukocyte-derived inflammatory mediators) in subjects with or at risk for atherosclerosis.

In subjects with asymptomatic atherosclerosis we found inverse relationships between cyclic guanosine monophosphate (cGMP) in platelets (mediator of NO activity) and both serum total cholesterol and plasma ET-1 suggesting that NO-mediated vasodilation may be impaired in hypercholesterolemia and that maintenance of vascular tone is achieved by a balance between NO and ET-1.

Another high risk group for atherosclerosis, NIDDM patients, showed higher plasma levels of ET-1 than healthy control subjects indicating a relationship between ET-1 and diabetic endothelial damage. NIDDM patients also showed higher intraplatelet cGMP levels than control subjects indicating enhanced NO activity in NIDDM.

In this study we also demonstrated in vivo relationships between activated leukocytes and platelet antiaggregation during the atherosclerotic process, and chronic endothelial and leukocyte activation during follow up of patients after acute cerebral ischemia. No evidence for monocyte activation was demonstrated in NIDDM patients, however.

The onset of menopause carries increased risk for atherosclerosis in women. This study suggests that the antiatherogenic properties of hormone replacement therapy (HRT) might occur through improvement of endothelial function; increased NO activity and reduced ET-1 levels, whereas we found no evidence for effects of HRT upon monocyte activation.

Details

Authors
  • Anwaar M Ibrahim
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Clinical Medicine

Keywords

  • Prostacyclin., Postmenopausal hormone replacement therapy, Nitric oxide, Endothelin, Diabetes mellitus, Cytokines, Cholesterol, Atherosclerosis, Cerebral ischemia, Cardiovascular system, Kardiovaskulära systemet
Original languageEnglish
QualificationDoctor
Awarding Institution
Supervisors/Assistant supervisor
  • [unknown], [unknown], Supervisor, External person
Award date1999 Jun 1
Publisher
  • Wallenberg Lab. Plan 2,University Hospital , Malmö, S-20502, Malmö, SWEDEN. After 1999-07-10 new address, P.O. Box 1042, Benghazi, Libya.
Publication statusPublished - 1999
Publication categoryResearch

Bibliographic note

Defence details Date: 1999-06-01 Time: 10:15 Place: University Hospital, Malmö, Sweden External reviewer(s) Name: Fagerberg, Björn Title: PhD Affiliation: Department of Medicine, Sahlgrenska Univerisity, Göteborg. ---