Skin Fibroblasts for Cholesterol Research

Dyslipidemia is robustly associated with atherosclerosis and cardiovascular
disease (CVD) risk. Studies of families displaying extreme tail lipid levels
have resulted in the discovery of key regulatory genes in LDL, HDL and TG
metabolism. However, studies of genetics only show association with lipid
traits, rather then mechanistic insights in metabolism. For this purpose in
vitro studies are necessary, preferably using patient material harbouring the
genetic variant under study. A well-established approach is the use of cultured
fibroblasts derived from a minimal invasive skin biopsy. These skin fibroblasts
are then used to study LDL uptake, receptor metabolism and cholesterol efflux.
All together this study will lead to a better understanding of cholesterol
metabolism and could lead to novel targets for therapy.

To obtain human fibroblasts from extreme dyslipidemia patients or patients with
premature atherosclerosis to study cholesterol metabolism.

Case control study in families with extreme dyslipidemia and/or premature
atherosclerosis, comparing fibroblasts of mutation carriers with fibroblasts
from wild-type family members.

Participants do not benefit from this study. Fibroblasts are cultured from a
small 3mm skin biopsy, after local anaesthesia, performed by a trained doctor.
Potential risks of the procedure are small and include bleeding, infection and
formation of a small scar. To minimise scar burden, the biopsy is taken from
the inside of the underarm. As participants are selected based on a putative or
proven genetic defect, insights from this study might lead to better treatment
options which could be of benefit for next generations.