After percutaneous angioplasty, in which occluded vessels are stretched open with a small balloon, 40 percent of patients are rehospitalised with a new constriction of the same vessel. In order to develop drugs against this new vessel constriction, Smeets investigated the processes which occur during the constriction of the vessel wall.
Smeets discovered that the protein haptoglobin inhibits certain enzymes involved in the breakdown of collagen. Collagen is the substance which stiffens the vessel walls. If after percutaneous angioplasty the vessel wall becomes constricted again, there is an increased production and breakdown of collagen.
Moreover, the medical researcher discovered that haptoglobin is produced locally, i.e. in the vessel wall. It was already known that the liver (thus not locally) produces this protein on a large scale and secretes it into the blood.
Furthermore, in cell cultures it has been demonstrated that haptoglobin plays an important role in the migration of cells. Cells which do not produce the protein, migrate less easily. The addition of haptoglobin to these cells enables them to migrate more easily, which results in an improved recovery of damaged blood vessels.
Damaged arteries from mice which cannot produce haptoglobin, recover less well than those from mice which can. Meanwhile a follow-up study has demonstrated that people who cannot produce haptoglobin do not have an increased risk for arteriosclerosis or the occlusion of blood vessels following percutaneous angioplasty.
Knowledge acquired about the mechanism by which damaged blood vessels recover, should eventually lead to the development of drugs that prevent 40 percent of patients from being rehospitalised with a constriction of the same blood vessel following percutaneous angioplasty.
For further information please contact Dr Mirjam Smeets (Department of Experimental Cardiology, Utrecht University), tel. 31-302-507-155, fax 31-302-522-693, e-mail: m.b.smeets@hli.azu.nl. The doctoral thesis was defended on 28 January 2003. Ms Smeets' supervisor was Prof. C. Borst.
The research was funded by the Netherlands Organisation for Scientific Research (NWO).