Exploring lipoprotein characteristics in human cardiometabolic disease
Härdfeldt, Jennifer
2024-05-24
09.00
Lecture Hall 4A Svartsjön, Novum, Karolinska Institutet, Flemingsberg
Inst för medicin, Huddinge / Dept of Medicine, Huddinge
Background: Atherosclerosis underlies most cases of cardiovascular disease (CVD)
which remains the principal cause of global mortality. CVD is significantly linked to
cardiometabolic diseases such as diabetes and obesity. These disorders precipitate a
cascade of metabolic dysregulations, including insulin resistance and altered lipid
metabolism, culminating in modified lipoprotein profiles.
Aim: Dissecting the characteristics of lipoproteins in the context of cardiometabolic
diseases and their contribution to atherogenesis.
Methods: The thesis is based upon five papers:
I.: Assessment of the impact of a novel potential therapeutic agent on hepatic lipid
metabolism using modified mRNA molecules in human hepatoma cell lines.
II.: Characterization of HDL in systemic arterial and coronary blood from patients
with Non-ST-Elevation Myocardial Infarction (NSTEMI).
III.: Evaluation of the influence of clustered cardiometabolic risk factors on the
functional properties of HDL.
IV.: Investigation into mechanisms of lipoprotein retention in type 2 diabetes through
analyses of lipoproteins in serum and interstitial fluid.
V.: Characterization of postprandial lipoproteins in serum and interstitial fluid
among healthy controls and individuals with type 2 diabetes.
Results: Key findings from the thesis papers were:
I.: The overexpression of TGIF1 protein in hepatoma cells induced a favorable lipid
profile alteration.
II.: Notable differences in HDL properties were found between coronary and
systemic circulation in the immediate aftermath of NSTEMI, unrelated to HDL
levels.
III.: Cardiometabolic risk factors exert a progressive negative impact on HDL
function, with a major contribution of abdominal obesity to alterations in reverse
cholesterol transport.
IV.: An apparent increase in vascular retention of atherogenic lipoproteins was seen
in type 2 diabetes, manifested by reduced ApoB-containing lipoproteins in
interstitial fluid concomittant with increased LDL affinity for arterial
proteoglycans. Similar changes were observed with increasing age in controls.
V.: Distinct postprandial alterations in serum and interstitial fluid revealed
atherogenic postprandial lipoprotein modifications in Type 2 diabetes.
Conclusion: This thesis accentuates the relationship between lipoprotein properties
and atherosclerosis in the context of cardiometabolic disorders. The insights highlight
the importance of qualitative lipoprotein evaluation beyond conventional quantitative
lipoprotein analysis. Such analyses should improve preventive strategies, including
cardiovascular risk assessment and new therapeutic interventions.