Calcification and C-reactive protein in atherosclerosis : effects of calcium blocking and cholesterol lowering therapy

Trion, A. (2006)

Doctoral Thesis

The presence of calcium deposits in the vessel wall is indicative of advanced atherosclerosis, and the extent of coronary calcification has been found to add prognostic significance to conventional risk factors of coronary artery disease. However, the mechanisms underlying vascular calcification are still obscure. The major objective of the work described in the first part of this thesis was to elucidate the mechanisms involved in atherosclerotic calcification. To study the process of VSMC calcification we developed and characterized an in vitro model of neonatal rat VSMC calcification. To investigate whether pharmacotherapy may affect vascular calcifications, we have studied the effect of a calcium antagonist (amlodipine) and a statin (atorvastatin) and their combination on this process. Inflammation is an important mechanism in the atherosclerotic process, and prospective and cross-sectional clinical and epidemiological studies have shown that CRP is consistently associated with CVD. The causality of CRP in atherosclerosis is discussed. To enable the study of the effect of CRP on atherosclerosis development in vivo, ApoE*3-Leiden/hCRP transgenic mice were generated and studied. The effects of a calcium antagonist (amlodipine), administered either alone or in combination with a statin (atorvastatin), on early atherosclerosis development in ApoE*3-Leiden/hCRP was investigated.

• Atherosclerosis
• Atherosclerotic calcification
• Calcium antagonist
• In vitro model
• Statin
• Transgenic mice
• Vascular smooth muscle cells

• All authors: Trion, A.
• Supervisor: Laarse, A. van der; Jukema, J.W.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2006-10-05
• ISBN (print): 9064640300, 9789064640308
• Court: LEI Universiteit Leiden
• Sponsorship: TNO Pfizer