Research team
Targeting the endothelium to treat arterial media calcification: investigation of endothelial cell contribution to arterial media calcification and preclinical evaluation of restoring NO bioavailability to halt this lethal disorder.
Abstract
Arterial media calcification (AMC) is defined as the accumulation of calcium-phosphate crystals in the medial layer of the arterial wall and is a major cardiovascular complication during aging and in patients with chronic kidney disease (CKD), diabetes and osteoporosis. AMC develops as a result of calcifying vascular smooth muscle cells (VSMC). Recently, however, the laboratory of Pathophysiology found strong evidence for the contribution of endothelial dysfunction (primarily characterized by reduced nitric oxide (NO) bioavailability) to AMC development. In this project, we will evaluate how endothelial cells (EC) can act as primary sensors of circulating triggers for AMC. We will use an in vitro EC/VSMC coculture model that will allow an in-depth investigation of the molecular effects of different calcification triggers on EC function, EC/VSMC interaction (with specific attention to NO signaling) and VSMC calcification. This detailed investigation of the endothelial phenotype during AMC could also potentially lead to the identification of new endothelial targets to treat AMC. Next, the therapeutic potential of restoring NO bioavailability in AMC will be preclinically evaluated in CKD and non-CKD induced AMC. In this way, we aim to contribute to the search for save, efficient arterial media calcification treatments, independent of patient population specific risk factors and not affecting bone health, as often seen with compounds that directly inhibit VSMC calcification.Researcher(s)
- Promoter: Verhulst Anja
- Co-promoter: Opdebeeck Britt
- Fellow: Adriaensen Saar
Research team(s)
Project type(s)
- Research Project
The role of the endothelial cell and its most important signaling molecule nitric oxide in the development of arterial media calcification, a lethal co-morbidity of aging related diseases.
Abstract
Arterial media calcification or the deposition of hydroxy-apatite (calcium-phosphate) crystals in the medial layer of the vessel wall occurs as a result of ageing and is accelerated in chronic kidney disease (CKD), diabetes and osteoporosis. Arterial media calcification has severe cardiovascular consequences including arterial stiffening, hypertension, impaired coronary perfusion, cardiac stroke and left ventricular hypertrophy, ultimately leading to heart failure. Consequently, this pathology has a high impact on patients' quality of live, economic activity and survival. Currently available therapies lack efficacy since they do not directly target the calcification process itself, however, act indirectly by controlling its risk factors. Furthermore, studies performed in the Laboratory of Pathophysiology repeatedly showed that compounds efficiently targeting arterial media calcification compromise physiological bone mineralization, which can be attributed to the fact that arterial media calcification resembles highly to physiological bone mineralization. This project aims to contribute to the search for save, efficient, arterial media calcification treatments, independent of patient population specific risk factors and not affecting bone health.Researcher(s)
- Promoter: Verhulst Anja
- Co-promoter: Opdebeeck Britt
- Fellow: Adriaensen Saar
Research team(s)
Project type(s)
- Research Project