Publikationsserver der RWTH Aachen University
Analyse der funktionellen Bedeutung von Sequenzveränderungen ausgewählter Matrixmetalloproteinasen für die Pathogenese von Dissektionen hirnversorgender Arterien
Abstract
dc:descriptionCervical artery dissection (CAD) is a leading cause of cerebral ischemia in young adults. Slight and heavy trauma is known as a cause of CAD. But in 50% of the patients no trauma can be determined. In round about 5% of all patients a connective tissue disorders such as Ehlers-Danlos syndrome is found. Ehlers-Danlos syndrome and Marfan syndrome are known to be risk factors for spontaneous CAD, so a genetic susceptibility for cervical dissections seems probable. Morphological investigations have shown alterations in the extracellular matrix (ECM) of affected vessel walls and the skin of patients. Matrix metalloproteinases (MMP) play a central role in the regulation of the ECM particularly in the regulation of the collagens. In the vessel wall of patients with CAD a lack of kollagen III was found but neither the kollagen itself nor expression of kollagen was modified. So modified expression of MMP could cause the alterations of the vessel wall by effecting the extracellular matrix. Prior studies in vascular pathologies have already shown evidence for an increased activity of MMP in the wall of affected blood vessels. Allelspecific effects on regulation of the MMP were found. In this study, we therefore investigated 5 polymorphisms in the promotor region of MMP genes (MMP 1,3,9 and 12) with a known increased expression of the corresponding enzyme as possible risk factors for spontaneous CAD. 70 Patients with CAD, that were medicated in the neurological clinic of the RWTH Aachen were compared with a group of control-persons by typification of the MMP 1, 3, 9 and 12 genes. Typification was realizey with PCR-sequencing, real-time-PCR and genescan. We did not find significant differences in frequencies of the analyzed polymorphisms in comparison the control group. Contrary to our expectation we found more alleles with higher promoter activity in the control group in the examination of MMP 1, 9 and 12 polymorphisms. These results are not statistically significant at all. A possible role for decreased MMP expression in CAD via indirect mechanisms cannot be excluded. However, the inclusion of more patients is needed to either strengthen or dismiss this second hypothesis. Also the TIMP (tissue inhibitors of matrix metalloproteinases) are an interesting group on enzymes that affect the ECM and are probably influenced by polymorphisms. More investigations on genetic polymorphisms affecting the MMP could lead to identification of risk factors and maybe find new ways of prevention and therapy of CAD.
Degree
thesis:*- Grantor dc:publisher
- Publikationsserver der RWTH Aachen University
- Year dc:date
- 2009
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Rölver, Susanne
- Contributors dc:contributor
-
- Klötzsch, Christof
Subjects
dc:subject × 8Rights
dc:rights- Statement dc:rights
-
- info:eu-repo/semantics/openAccess
- Language dc:language
- ger