Unit:
Department of ChemistryLibrary of the School of Science
Author:
Gkolfinopoulou Christina
Dissertation committee:
Θωμάς Μαυρομούστακος, Καθηγητής, Τμήμα Χημείας, ΕΚΠΑ
Αγγελική Χρόνη, Ερευνήτρια Α΄, Ινστιτούτο Βιοεπιστημών και Εφαρμογών, ΕΚΕΦΕ «Δημόκριτος»
Ντία Γαλανοπούλου, Καθηγήτρια, Τμήμα Χημείας, ΕΚΠΑ
Αθανάσιος Γκιμήσης, Αναπληρωτής Καθηγητής, Τμήμα Χημείας, ΕΚΠΑ
Παναγιώτα Μαρκάκη, Αναπληρώτρια Καθηγήτρια, Τμήμα Χημείας, ΕΚΠΑ
Ουρανία Τσιτσιλώνη, Αναπληρώτρια Καθηγήτρια, Τμήμα Βιολογίας, ΕΚΠΑ
Ευαγγελία Εμμανουηλίδου, Επίκουρη Καθηγήτρια, Τμήμα Χημείας, ΕΚΠΑ
Original Title:
Δομικός και λειτουργικός χαρακτηρισμός φυσικών μεταλλάξεων της απολιποπρωτεΐνης Α-Ι. Μελέτη των αθηροπροστατευτικών ιδιοτήτων της λιποπρωτεΐνης υψηλής πυκνότητας (HDL).
Translated title:
Structural and functional characterization of natural mutations of apolipoprotein A-I. Study of atheroprotective functions of high density lipoprotein (HDL).
Summary:
Although low levels of high density lipoprotein-cholesterol (HDL-C) are considered an independent risk factor for the development of cardiovascular disease (CVD), recent studies suggested that HDL-C levels alone cannot safely predict CVD risk and that HDL functionality may be more relevant for atheroprotection. Apolipoprotein A-I (apoA-I) constitutes the major protein component of HDL and plays a central role in HDL biogenesis, structure and function. HDL exerts a series of antiatherogenic properties, such as the ability to promote cholesterol efflux from artery wall macrophages, antioxidative ability, anti-inflammatory effects, as well as capacity for maintenance of endothelial integrity.
In the current PhD thesis it was evaluated whether HDL antiatherogenic properties are impaired in patients with ankylosing spondylitis (AS), a disease associated with increased CVD risk. The obtained findings show that HDL from patients with AS displays impaired antiatherogenic properties. Attenuation of HDL properties may constitute a molecular link between AS and CVD.
Additionally, in the current PhD thesis it was examined the structure-function relationship of human apoA-I/HDL. Specifically, it was investigated the effect of three naturally occurring point mutations in human apoA-I (L144R, A164S and L178P) that have been associated with increased CVD risk or/and low HDL-C levels, on structural integrity, by using biophysical techniques and on atheroprotective functions of apoA-I or HDL, by using in vitro and cell-based assays. In addition, it was examined the effect of a novel apoA-I mutation (V19L) that has been associated with increased HDL-C levels and decreased CVD risk, on structural integrity and on atheroprotective functions of apoA-I or HDL. Overall, the obtained data suggest that the insertion of point mutations in the molecule of apoA-I can cause changes to protein conformation and antiatherogenic properties of apoA-I and HDL. It is proposed that these changes may underlie the alterations in HDL-C levels or/and CVD risk, that have been observed in carriers of L144R, A164S, L178P and V19L apoA-I mutations.
Main subject category:
Science
Keywords:
apolipoprotein A-I, apolipoprotein A-I structure, HDL, antiatherogenic properties of HDL, cardiovascular disease
Number of index pages:
13
Number of references:
497
