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Harangi et al. HDL structure and function in dyslipidemia

[1]
composition . Therefore, the subfraction distribution in this patient population. Additionally, combined
of HDL has implications for their functions. Although forms of hyperlipidemia often require combined drug
the compositional and functional heterogeneity of HDL therapy. At the same time, it must be noted that lipid
particles is well known, HDL is often regarded as a lowering agents, such as statins [12,13] , fibrates [14]
single entity characterized by measurement of HDL- and ezetimibe [15] have a significant effect on HDL
cholesterol (HDL-C) levels. Previous epidemiological composition and function. Consequently, evaluating
studies have clearly shown that levels of HDL-C are the effect of various lipid abnormalities on HDL
inversely associated with the risk of coronary artery properties in patients on lipid lowering therapy can be
disease and its thrombotic complications [2,3] . Over misleading [16] .
the last few decades, substantial progress has been
made in understanding how the HDL particle exerts Therefore, we investigated the structural and some
protective effects on the vessel wall. HDL and its functional HDL properties in newly diagnosed,
main protein constituent, apolipoprotein A1 (ApoA1) untreated dyslipidemic patients and in healthy controls
is protective in processes involved in atherogenesis, to evaluate the effect of dyslipidemia on the structural
including mediation of reverse cholesterol transport, and functional properties of HDL characterized by the
protection against oxidative stress, and inhibition of serum levels of HDL subfractions and MPO, PON1
cytokine-induced expression of cellular adhesion paraoxonase and arylesterase activities and PON1
molecules on endothelial cells. However, under phenotyping. We hypothesized that the level and
particular circumstances, HDL particles may become ratio of large HDL subfractions are higher, and the
dysfunctional caused by the loss of antioxidant and level and ratio smaller HDL subfractions are lower in
anti-inflammatory proteins in combination with a dyslipidemic subjects compared to healthy controls. A
gain of acute phase proteins and some further pro- lower number of smaller HDL subfractions may result
inflammatory components. This pro-inflammatory, in lower PON activities and higher MPO levels.
dysfunctional HDL is unable to protect low-density
lipoprotein (LDL) from oxidation and to prevent METHODS
monocyte migration into the vessel wall induced by
[4]
oxidized LDL particles . Myeloperoxidase (MPO) Study population
mediates the oxidation of ApoA1 that creates a The study protocol was approved by local and regional
dysfunctional HDL particle, which activates nuclear ethics committees and carried out in accordance
factor kappa-B and promotes inflammation in the with the Declaration of Helsinki of World Medical
[5]
vessel wall . MPO level and its role in oxidative Association. All investigated subjects gave their written
stress and inflammation has been implicated in the informed consent to participate in the study. We
pathophysiology of cardiovascular diseases such as enrolled eighty-one newly diagnosed, untreated patient
[6]
coronary artery disease . Human paraoxonase-1 with Fredrickson type IIa and IIb hyperlipidemia that
(PON1) is a calcium-dependent lactonase that were referred to our lipid outpatient clinic at Department
is produced by the liver and almost exclusively of Internal Medicine, University of Debrecen. Physical
[7]
associated with HDL . Although hydrolysis of examination and carotid ultrasound were performed
homocysteine thiolactone might represent a major regularly. Further vascular imaging techniques (Doppler
[8]
physiologic function of PON1 , several further ultrasound and computer tomography) were performed
substrates have been described including other in case of complaints or abnormal physical and
[9]
[7]
lactones , organophosphates and lipid peroxides . electrocardiography examinations.
Interestingly, some previous studies proved that PON1
is predominantly associated to the smaller and denser We excluded patients with pre-existing vascular
HDL3 subfractions, and PON1 activity of HDL2 was complications from the study. Vascular complications
only 4% of that in HDL3 [10] . Furthermore, previous data were defined as ischemic heart disease (myocardial
indicate that MPO, PON1 and HDL from a functional infarction or coronary sclerosis), ischemic cerebrovascular
ternary complex in which MPO and PON1 inhibit each disease (ischemic stroke, transient ischemic attack,
other’s activity demonstrating the dysfunction of the carotid artery stenosis/occlusion) and peripheral
HDL particle [11] . arterial disease. Vascular complications were
established by patient history or upon the results of
Dyslipidemia characterized by high levels of imaging techniques. Any lesions with measurable
triglyceride, total and LDL cholesterol is an intravascular stenosis were defined as clinically
established risk factor for coronary heart disease. significant. Further exclusion criteria included
Therefore, to reduce the risk of cardiovascular previous and ongoing lipid lowering therapy, chronic
complications lipid lowering treatment is widely used inflammatory conditions, autoimmune disease, and

Vessel Plus ¦ Volume 1 ¦ December 28, 2017 167