The Ivestigation of Relationship between Dysfunctional Hdl with Caroti̇d Stenosis Ratio and Atherosclerosi̇c Plaque Morphology in the Patients Diagnosed with Extracranial Carotid Stenosi̇s


Thesis Type: Expertise In Medicine

Institution Of The Thesis: Ankara Yildirim Beyazit University, Tıp Fakültesi, Tıbbi Biyokimya Ana Bilim Dalı, Turkey

Approval Date: 2019

Thesis Language: Turkish

Student: Almila ŞENAT

Supervisor: ÖZCAN EREL

Abstract:

Cerebrovascular diseases are the second leading cause of death worldwide. The most common cerebrovascular disease is cerebral artery stenosis. The formation mechanism of carotid artery stenosis, which has a high prevalence in our country, is atherosclerosis as well as coronary artery stenosis. Atherosclerosis is a slowly progressive chronic disease that begins in the first years of life. Atherosclerosis, which develops following the endothelial damage in the carotid artery branches and accelerates its progression, leads to the formation of larger lesions with the contribution of oxidative steres. Oxidative stress and inflammation coexist in the atherosclerosis pategenesis. Circulating HDL particles are known as anti-atherogenic lipoproteins due to the reverse cholesterol transfer they perform towards the liver in peripheral tissues. The proteome portion of the HDL particles also provides these particles with anti-oxidant properties. The anti-oxidant properties of HDL particles come from the PON enzyme on the HDL particle. The PON enzyme hydrolyzes oxidized lipit molecules on HDL and LDL particles whose are altered by being oxidized particles in atherosclerotic lesions and circulating and removes them from lipoproteins. With the onset of the inflammatory process, oxidant molecules are produced by various mechanisms. MPO enzyme and its products are the leading ones. MPO creates oxidative modification of HDL particles with oxidant molecules formed as a result of MPO activity and prevents HDL from performing its natural functions. Such modified HDL particles are defined as dysfunctional HDL. In this study, we investigated whether there is a relationship between stenosis rates and plaque morphology in patients with carotid artery stenosis. For this purpose, MPO, PON, ARE, LOOH and ferrooxidase were measured in serum of control and stenosis groups. MPO / PON ratio, which is considered as an indicator of dysfunctional HDL, was calculated and its relationship with carotid artery stenosis and plaque morphology was evaluated. In conclusion, in this study, increased MPO enzyme activity and decreased PON enzyme activity and high LOOH levels were obtained in stenosis group. According to our results, we think that finding increased inflammation in atherosclerosis and high MPO enzyme activities, decreased activity of PON antagonist to MPO effect, therefore and decreased hydrolysis of circulating oxidized lipoproteins and oxidized lipits in atherosclerotic lesions induce to HDL particles become dysfunctioning of HDL particles. In this context, the increase in LOOH levels, which is the substrate of PON enzyme as a result of decreased PON enzyme activity, is shown by the higher LOOH / PON ratios in the stenosis group compared to the control group. When the lesion gets more and more complex, The relationship between plaque morphology and MPO enzyme activity and PON enzyme activities correlates with high MPO activity versus decreased PON activity. There was no correlation between MPO / PON ratios which we evaluated dysfunctional HDL and plaque morphology. However, there was a strong correlation between MPO / ARE ratios and plaque morphology. As the plaque structure became more complex, MPO / ARE ratios were found to increase gradually. Our study is important for the evaluation of dysfunctional HDL in carotid artery stenosis and to determine its association with plaque morphology.