Danish Medical Bulletin - No. 2. June 2004. Vol. 51 Page 220.

ABSTRACT OF PhD DISSERTATION

The diabetic macroangiopathy considered from a vascular biological point of view

Hyaluronic acid and its receptor's (CD44) formation and influence on the vessel wall.

Kirsten Schultz, M.Sc.

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This PhD dissertation was accepted by the Faculty of Health Science of the University of Aarhus, and defended on March 12, 2004.

Official opponents: Hans Oxlund, John Chemnitz, and Gitte V. Eriksen.

Tutors: Thomas Ledet and Lars Melholt Rasmussen.

Correspondance: Kirsten Schultz, Skovlundgårdsvej 234, DK-8260 Viby J.

Dan Med Bull 2004;51:220.

ABSTRACT

The studies behind this thesis were carried out at the Laboratory of Biochemical Pathology, Århus Sygehus. The thesis is based on an original paper investigating the effects of diabetic-like concentrations of components of the metabolic disorders of diabetes mellitus.

In 1971 the term diabetic macroangiopathy was introduced to emphasize the presence of non-atherosclerotic large vessel disease in diabetic patients. Diabetic macroangiopathy does not indicate a set of abnormalities restricted to certain areas of the large vessels as in atherosclerosis, but a number of specific vessel wall changes seen in the entire large vessel system. These changes are regarded to be a consequence of the diabetic metabolism. In areas of aorta without atherosclerotic plaque an increased proportion of HA is observed in tunica media in diabetic individuals. Furthermore the HA receptor, CD44, is induced on vascular SMCs after arterial wall injury and may mediate proliferation and migration of SMCs into the tunica intima. Thereby HA and its receptor CD44 may be an important factor in the pathogenesis of cardiovascular disease in diabetic patients.

The aim of this thesis was to evaluate the influence of diabetic-like concentrations of glucose, insulin, IGF-1 and hGH on the expression of CD44std and the variant isoforms CD44v3 and CD44v6 on the arterial SMCs in vitro. Furthermore the effect of diabetic - like concentrations of the four metabolic components on SMC migration is examined to determine whether CD44 receptor is important for SMC migration.

In conclusion, these in vitro studies confirm that the CD44 receptor plays a role in SMC migration at diabetic-like concentrations of glucose, insulin and IGF-1. Therefore CD44 receptor might contribute to SMC accumulation in the intima in patients with diabetes. Furthermore the results support the notion that insulin might have a significant influence on HA binding and thereby be a factor modulating vascular SMC function during the development of large vessel disease in diabetic subjects. Finally the expression of CD44 and CD44v3 showed significant but small changes after metabolic manipulation with some of the components.
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