Structural determinants in ApoA-I amyloidogenic variants explain improved cholesterol metabolism despite low HDL levels.
- Rita Del Giudice,
- Joan Domingo-Espín,
- Ilaria Iacobucci,
- Oktawia Nilsson,
- Maria Monti,
- Daria Maria Monti,
- Jens O Lagerstedt
Biochim Biophys Acta 2017 Dec 6;1863(12):3038-3048. Epub 2017 Sep 6.
Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden. Electronic address:
Twenty Apolipoprotein A-I (ApoA-I) variants are responsible for a systemic hereditary amyloidosis in which protein fibrils can accumulate in different organs, leading to their failure. Several ApoA-I amyloidogenic mutations are also associated with hypoalphalipoproteinemia, low ApoA-I and high-density lipoprotein (HDL)-cholesterol plasma levels; however, subjects affected by ApoA-I-related amyloidosis do not show a higher risk of cardiovascular diseases (CVD). The structural features, the lipid binding properties and the functionality of four ApoA-I amyloidogenic variants were therefore inspected in order to clarify the paradox observed in the clinical phenotype of the affected subjects. Read More