Apolipoprotein B and oxLDL levels in plasma of patients with diabetes, cardiovascular disease, and COVID-19
Elevated levels of low-density lipoprotein (LDL-X) cholesterol, apolipoprotein B (ApoB), and especially oxidized LDL in plasma are associated with an increased risk of cardiovascular disease (CVD). The aim of the study was to determine the levels of ApoB and oxLDL in the blood of patients with dia...
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irk-123456789-1848252022-07-18T01:26:18Z Apolipoprotein B and oxLDL levels in plasma of patients with diabetes, cardiovascular disease, and COVID-19 Tronko, M.D. Cherviakova, S.A. Pushkarev, V.V. Belchina, Y.B. Kovzun, O.I. Pushkarev, V.M. Sokolova, L.K. Біохімія Elevated levels of low-density lipoprotein (LDL-X) cholesterol, apolipoprotein B (ApoB), and especially oxidized LDL in plasma are associated with an increased risk of cardiovascular disease (CVD). The aim of the study was to determine the levels of ApoB and oxLDL in the blood of patients with diabetes mellitus (DM), CVD and COVID-19. ApoB and oxLDL were determined using enzyme-linked immunosorbent assay kits (Elabscience, USA). The measurements were performed at an optical wavelength of 450 nm. It was found that ApoB and oxLDL levels in the blood of patients with diabetes and, especially, with COVID-19 are substantially higher than in the blood of healthy people. Blood levels of ApoB and oxLDL are higher in patients with both COVID-19 and diabetes or CVD as com pared to patients with COVID-19 without comorbidities. Thus, the levels of ApoB and oxidized LDL may be the promising markers of severe COVID-19. Підвищений рівень холестерину ліпопротеїнів низької щільності (ЛПНЩ-Х), аполіпопротеїну В (ApoВ), який в них міститься, та, особливо, окиснених ЛПНЩ у плазмі крові асоціюється із підвищеним ризиком розвитку серцево-судинних захворювань (ССЗ). Метою роботи було визначення рівня ApoВ та окиснених ЛПНЩ у крові хворих на цукровий діабет (ЦД), ССЗ та COVID-19. ApoВ та окиснені ЛПНЩ визначали за допомогою наборів для імуноферментного аналізу (Elabscience, США). Вимірювання проводили при оптичній довжині хвилі 450 нм. Встановлено, що рівень ApoВ та окиснених ЛПНЩ у крові хворих на ЦД і, особливо, з COVID-19 значно вищий, ніж у крові здорових людей. Рівень ApoВ та окиснених ЛПНЩ у крові вище у пацієнтів і з COVID-19 і з діабетом або ССЗ порівняно з пацієнтами з COVID-19 без супутніх захворювань. Таким чином, рівень ApoВ та окиснених ЛПНЩ може бути перспективним маркером тяжкого COVID-19. 2021 Article Apolipoprotein B and oxLDL levels in plasma of patients with diabetes, cardiovascular disease, and COVID-19 / M.D. Tronko, S.A. Cherviakova, V.V. Pushkarev, Y.B. Belchina, O.I. Kovzun, V.M. Pushkarev, L.K. Sokolova // Доповіді Національної академії наук України. — 2021. — № 6. — С. 126-130. — Бібліогр.: 12 назв. — англ. 1025-6415 DOI: doi.org/10.15407/dopovidi2021.06.126 http://dspace.nbuv.gov.ua/handle/123456789/184825 616.379-008.64:616.12:616.98 en Доповіді НАН України Видавничий дім "Академперіодика" НАН України |
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Digital Library of Periodicals of National Academy of Sciences of Ukraine |
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Біохімія Біохімія |
| spellingShingle |
Біохімія Біохімія Tronko, M.D. Cherviakova, S.A. Pushkarev, V.V. Belchina, Y.B. Kovzun, O.I. Pushkarev, V.M. Sokolova, L.K. Apolipoprotein B and oxLDL levels in plasma of patients with diabetes, cardiovascular disease, and COVID-19 Доповіді НАН України |
| description |
Elevated levels of low-density lipoprotein (LDL-X) cholesterol, apolipoprotein B (ApoB), and especially oxidized
LDL in plasma are associated with an increased risk of cardiovascular disease (CVD). The aim of the study was to
determine the levels of ApoB and oxLDL in the blood of patients with diabetes mellitus (DM), CVD and COVID-19.
ApoB and oxLDL were determined using enzyme-linked immunosorbent assay kits (Elabscience, USA). The measurements
were performed at an optical wavelength of 450 nm. It was found that ApoB and oxLDL levels in the
blood of patients with diabetes and, especially, with COVID-19 are substantially higher than in the blood of
healthy people. Blood levels of ApoB and oxLDL are higher in patients with both COVID-19 and diabetes or CVD as
com pared to patients with COVID-19 without comorbidities. Thus, the levels of ApoB and oxidized LDL may be the
promising markers of severe COVID-19. |
| format |
Article |
| author |
Tronko, M.D. Cherviakova, S.A. Pushkarev, V.V. Belchina, Y.B. Kovzun, O.I. Pushkarev, V.M. Sokolova, L.K. |
| author_facet |
Tronko, M.D. Cherviakova, S.A. Pushkarev, V.V. Belchina, Y.B. Kovzun, O.I. Pushkarev, V.M. Sokolova, L.K. |
| author_sort |
Tronko, M.D. |
| title |
Apolipoprotein B and oxLDL levels in plasma of patients with diabetes, cardiovascular disease, and COVID-19 |
| title_short |
Apolipoprotein B and oxLDL levels in plasma of patients with diabetes, cardiovascular disease, and COVID-19 |
| title_full |
Apolipoprotein B and oxLDL levels in plasma of patients with diabetes, cardiovascular disease, and COVID-19 |
| title_fullStr |
Apolipoprotein B and oxLDL levels in plasma of patients with diabetes, cardiovascular disease, and COVID-19 |
| title_full_unstemmed |
Apolipoprotein B and oxLDL levels in plasma of patients with diabetes, cardiovascular disease, and COVID-19 |
| title_sort |
apolipoprotein b and oxldl levels in plasma of patients with diabetes, cardiovascular disease, and covid-19 |
| publisher |
Видавничий дім "Академперіодика" НАН України |
| publishDate |
2021 |
| topic_facet |
Біохімія |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/184825 |
| citation_txt |
Apolipoprotein B and oxLDL levels in plasma of patients with diabetes, cardiovascular disease, and COVID-19 / M.D. Tronko, S.A. Cherviakova, V.V. Pushkarev, Y.B. Belchina, O.I. Kovzun, V.M. Pushkarev, L.K. Sokolova // Доповіді Національної академії наук України. — 2021. — № 6. — С. 126-130. — Бібліогр.: 12 назв. — англ. |
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Доповіді НАН України |
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126
ОПОВІДІ
НАЦІОНАЛЬНОЇ
АКАДЕМІЇ НАУК
УКРАЇНИ
ISSN 1025-6415. Dopov. Nac. akad. nauk Ukr. 2021. № 6: 126—130
Ц и т у в а н н я: Tronko M.D., Cherviakova S.A., Pushkarev V.V., Belchina Y.B., Kovzun O.I., Pushkarev V.M.,
Sokolova L.K. Apolipoprotein B and oxLDL levels in plasma of patients with diabetes, cardiovascular di-
sease, and COVID-19. Допов. Нац. акад. наук Укр. 2021. № 6. С. 126—130.
https://doi.org/10.15407/dopovidi2021.06.126
Hydrophobic lipids are insoluble in plasma, and, for the delivery to tissues, they have to be
packaged into lipoproteins with cholesterol esters and triglycerides in the core and phospho-
lipids, free cholesterol, and apolipoproteins on the surface. The hydrophobic core of low-density
lipoprotein (LDL) is made of about 170 triglycerides, 1500 cholesterol esters, a hydrophilic coat
composed of 700 molecules of phospholipids, about 500 molecules of unesterified cholesterol,
and a single large copy of the ApoB of 500 kDa [1]. Apolipoprotein B is the primary apolipopro-
https://doi.org/10.15407/dopovidi2021.06.126
https://doi.org/10.15407/dopovidi2021.06.126
UDC 616.379-008.64:616.12:616.98
M.D. Tronko, https://orcid.org/0000-0001-7421-0981
S.A. Cherviakova, https://orcid.org/0000-0002-6917-5736
V.V. Pushkarev, https://orcid.org/0000-0001-5940-5510
Y.B. Belchina, https://orcid.org/0000-0002-4289-8977
O.I. Kovzun, https://orcid.org/0000-0001-8164-7671
V.M. Pushkarev, https://orcid.org/0000-0003-0347-7771
L.K. Sokolova, https://orcid.org/0000-0003-0011-0106
V.P. Komisarenko Institute of Endocrinology and Metabolism of the NAMS of Ukraine, Kyiv
E-mail: pushkarev.vm@gmail.com
Apolipoprotein B and oxLDL levels in plasma of patients
with diabetes, cardiovascular disease, and COVID-19
Presented by Corresponding Member of the NAS of Ukraine M.D. Tronko
Elevated levels of low-density lipoprotein (LDL-X) cholesterol, apolipoprotein B (ApoB), and especially oxidized
LDL in plasma are associated with an increased risk of cardiovascular disease (CVD). The aim of the study was to
determine the levels of ApoB and oxLDL in the blood of patients with diabetes mellitus (DM), CVD and COVID-19.
ApoB and oxLDL were determined using enzyme-linked immunosorbent assay kits (Elabscience, USA). The mea-
surements were performed at an optical wavelength of 450 nm. It was found that ApoB and oxLDL levels in the
blood of patients with diabetes and, especially, with COVID-19 are substantially higher than in the blood of
healthy people. Blood levels of ApoB and oxLDL are higher in patients with both COVID-19 and diabetes or CVD as
com pared to patients with COVID-19 without comorbidities. Thus, the levels of ApoB and oxidized LDL may be the
promising markers of severe COVID-19.
Keywords: COVID-19, type 2 diabetes, cardiovascular disease, apolipoprotein B, oxidized LDL.
БІОХІМІЯ
BIOCHEMISTRY
127ISSN 1025-6415. Допов. Нац. акад. наук Укр. 2021. № 6
Apolipoprotein B and oxLDL levels in plasma of patients with diabetes, cardiovascular disease, and COVID-19
tein and is the carrier for the following lipids: chylomicrons, LDL, very low-density lipo protein
(VLDL), intermediate-density lipoprotein (IDL), and lipoprotein (a). ApoB is not found in high-
density lipoproteins (HDL), the latter are reconstituted into lipoproteins with ApoA. Hepatic
ApoB has a molecular mass of 540000 Da. There are two circulating forms of ApoB, ApoB48 (from
small intestine) and ApoB100 (from liver) [2].
Under oxidative stress, the oxidation of LDL occurs by the process of lipid peroxidation
primarily involving the phospholipid molecules. Under pathological conditions, ApoB-con-
taining lipoproteins in the plasma penetrate through the damaged endothelium into vascular
subendothelial intima getting oxidized by ROS. Thus, the LDL is modified into oxLDL [1].
It has been found that increased levels of low-density lipoprotein cholesterol (LDL-C), apo-
lipoprotein B, and especially oxLDL in plasma are associated with an increased risk of developing
cardiovascular diseases (CVD). The ApoB/ApoA1 ratio has been found to be asso ciated with
type 2 diabetes and has been proposed as a novel biomarker for its prediction [3]. Meta-analysis
also shows that increased ApoB and decreased ApoA1 levels, as well as the ApoB/A1 ratio,
are risk factors for the first ischemic stroke [4].
Materials and Methods. The study was conducted in the diabetology department of the
Institute. The study protocol was approved by the Institute’s ethics committee. All patients
signed informed consent to conduct the further diagnostic and research study.
Blood was obtained by standard venipuncture and stored in EDTA vacutainer tubes. Plasma
was separated by centrifugation within 10 min after blood sampling. The samples were stored
at –80 C until use. ApoB/oxLDL was determined (n 81) using enzyme-linked immuno-
sorbent assay (ELISA) kit (Elabscience, USA). The measurement was carried out at an optical
wavelength of 450 nm on an immunoenzymatic plate analyzer Stat Fax 3200 (Awareness Tech-
nology, USA).
Glycated hemoglobin was determined using one HbA1c FS kit (DiaSys Diagnostic Systems
GmbH (Germany). The measurement was carried out at an optical wavelength of 660 nm.
Statistical analysis and data presentation were performed using the Origin 7.0 software.
The results of the study are presented as M ± m. To compare the data groups, Student’s t-test
was used. Values of 0.05P were considered as significant.
Results and discussion. The blood plasma of 60 type 2 diabetes patients and 21 patients
with diabetes, СVD and COVID-19 was used. As a control, we used the blood of healthy people
(n 7) without concomitant diseases, representative of age. 4 patients had CVD in the anam nesis.
The level of Hb1Ac in diabetic patients was 9.62 ± 0.27; BMI — 30.69 ± 1.06 kg/m2. The fasting
glucose content in the blood of patients with COVID-19 and diabetes was 9.6 ± 0.92 mmol/l, at
the time of discharge — 6.72 ± 0.62 mmol/l. Average O2 saturation was 87.3 ± 0.7 %, which in-
dicates a severe course of the disease.
The average level of ApoB in the blood of healthy people was 1.05 g/L, within the normal
range (norm: 0.55—1.3 g/L for men, and 0.6—1.4 g/L for women) (Table). In diabetic patients,
this indicator is higher — 1.15 g/L — closer to the upper limit of the norm. In patients with
COVID-19, the content of ApoB in blood is substantially higher, than control and norm values
(see Table, lines 3-6). It is worth to note the difference between patients with COVID-19
without concomitant diseases and COVID-19 with diabetes and especially CVD (see Table, line
5 vs. lines 4 and 6).
128 ISSN 1025-6415. Dopov. Nac. akad. nauk Ukr. 2021. № 6
M.D. Tronko, S.A. Cherviakova, V.V. Pushkarev, Y.B. Belchina, O.I. Kovzun, V.M. Pushkarev, L.K. Sokolova
Almost the same pattern was observed with oxLDL (Table). In diabetic patients, the amount
of oxLDL is higher than that of control level. In patients with COVID-19, the content of oxLDL in
blood is much higher than control and diabetic patients levels (see Table, lines 3-6). There was
also the significant difference between patients with COVID-19 without concomitant diseases
and COVID-19 with diabetes and and CVD (see Table, line. 5 vs. lines 4 and 6). Thus, the amount
of ApoB and LDL derivatives, oxLDL, changes in the blood of diabetic and COVID-19 patients
almost synchronously.
It has been proven that a high content of low-density lipoproteins (LDL) causes the accu-
mulation of cholesterol on the walls of blood vessels, significantly increasing the risk of athe ro-
sclerosis (AS) and CVD [5-7]. Due to the fact that ApoB is the main protein of LDL, which is, in
turn, the main carrier of cholesterol to the cells, the determination of its concentration specifies
the degree of risk of developing coronary heart disease. The concentration of ApoB in the blood
is now considered a more reliable indicator of the risk of developing AS, than total choleste-
rol (TC) or LDL-cholesterol (LDL-C). Along with the determination of the ApoB concen-
tration, the content of apolipoprotein A1 should also be determined. If the ratio of the concen-
trations of ApoB to ApoA1 is more than 1, then the risk of developing coronary heart disease is
very high. It was proposed to set the limits of the norm for ApoB more than 1.2 g/L. For risk
groups, it is recommended to maintain the ApoB content of less than 0.9 g/L regardless of gender.
With regard for the limit values of the ApoB/ApoA1 ratio, it can be used to determine the level of
risk for men <0.9, and for women <0.8) [6, 8].
AS is characterized as a chronic inflammatory response to cholesterol deposition in arteries.
LDL, especially the oxidized form — oxLDL, plays a crucial role in the occurrence and deve-
Plasma ApoB and oxLDL levels of patients with diabetes, CVD and COVID-19
No. Groups ApoB, g/l m n
1 Contr. 1.052 0.062 7
2 DM 1.154 0.036* 60
3 COVID-19 average 2.324 0.089** 21
4 COVID-19 +DM 2.433 0.087** 16
5 COVID-19, healthy 2.123 0.064**+ 5
6 COVID-19 +CVD 2.620 0.148** 4
No. Groups oxLDL, pg/ml m n
1 Contr. 70.45 12.86 7
2 DM 102.07 7.87* 60
3 COVID-19 total 256.54 7.01** 21
4 COVID-19 +DM 268.46 5.55** 16
5 COVID-19, healthy 232.44 9.8**+ 5
6 COVID-19 +CVD 281.50 8.02** 4
Notes. 1 — control; 2 — patients with diabetes mellitus; 3 — average data for all patients with COVID-19;
4 — patients with COVID-19 and diabetes; 5 — patients with COVID-19 without concomitant diseases (n 5);
6 — patients with COVID-19 and CVD (n 4). M ± m. There were significant differences between control
and other groups: * P < 0.05; ** P << 0.001; + differences from groups 4, 6 are significant, P < 0.05
129ISSN 1025-6415. Допов. Нац. акад. наук Укр. 2021. № 6
Apolipoprotein B and oxLDL levels in plasma of patients with diabetes, cardiovascular disease, and COVID-19
lopment of AS by inducing endothelial cell dysfunction, attracting monocytes/macrophages,
and promoting chronic inflammation. Macrophages engulf oxLDL to form foam cells that ulti-
mately release pro-inflammatory cytokines and exacerbate local inflammation [7, 9].
We showed that both ApoB and oxLDL levels increased with high significance (P 5.85 · 10–8
and 2.46·10–11, respectively) that evidenced the rise of CVD risk.
The dyslipidemia associated with SARS has been repeatedly confirmed. However, other
authors found that the levels of serum TC, HDL- and LDL-cholesterol were significantly lower in
the COVID-19 patients as compared with normal subjects [9, 10]. It was concluded that patients
with COVID-19 develop hypolipidemia, when symptoms are mild, and that hypolipidemia wor-
sens with disease severity [10]. But those authors use “hypolipidemia” to refer to patients
with total cholesterol <174 mg/dL. This definition of hypolipidemia is improper and substan-
tially wrong in the absence of a genetic diagnosis. The prevalence of subjects at high cardiovascu-
lar risk could explain the observed findings on LDL-C. Low levels of LDL-C in this group were
likely due to a more intensive lipid-lowering treatment [11]. In addition, we studied the content
of ApoB, not LDL-C, and they may have different dynamics. The level of ApoA1 was significant-
ly decreased in the blood of COVID-19 patients [12].
Conclusions. The levels of ApoB and oxLDL in the blood of patients with diabetes and, es-
pecially, COVID-19 were significantly higher than in the blood of healthy people.
There were differences between patients with COVID-19 without concomitant diseases
and COVID-19 with diabetes or CVD.
The levels of ApoB and oxLDL may be the promising markers for COVID-19.
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M.D. Tronko, S.A. Cherviakova, V.V. Pushkarev, Y.B. Belchina, O.I. Kovzun, V.M. Pushkarev, L.K. Sokolova
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Received 24.06.2021
М.Д. Тронько, https://orcid.org/0000-0001-7421-0981
С.А. Червякова, https://orcid.org/0000-0002-6917-5736
В.В. Пушкарьов, https://orcid.org/0000-0001-5940-5510
Ю.Б. Бельчина, https://orcid.org/0000-0002-4289-8977
О.І. Ковзун, https://orcid.org/0000-0001-8164-7671
В.М. Пушкарьов, https://orcid.org/0000-0003-0347-7771
Л.К. Соколова, https://orcid.org/0000-0003-0011-0106
ДУ “Інститут ендокринології та обміну речовин ім. В.П. Комісаренка НАМН України”, Київ
E-mail: pushkarev.vm@gmail.com
РІВЕНЬ АПОЛІПОПРОТЕЇНУ B ТА oxLDL
У ПЛАЗМІ ПАЦІЄНТІВ ІЗ ДІАБЕТОМ,
СЕРЦЕВО-СУДИННИМИ ЗАХВОРЮВАННЯМИ ТА COVID-19
Підвищений рівень холестерину ліпопротеїнів низької щільності (ЛПНЩ-Х), аполіпопротеїну В (ApoВ),
який в них міститься, та, особливо, окиснених ЛПНЩ у плазмі крові асоціюється із підвищеним ризи ком
розвитку серцево-судинних захворювань (ССЗ). Метою роботи було визначення рівня ApoВ та окис-
нених ЛПНЩ у крові хворих на цукровий діабет (ЦД), ССЗ та COVID-19. ApoВ та окиснені ЛПНЩ ви-
значали за допомогою наборів для імуноферментного аналізу (Elabscience, США). Вимірювання про во-
дили при оптичній довжині хвилі 450 нм. Встановлено, що рівень ApoВ та окиснених ЛПНЩ у крові
хворих на ЦД і, особливо, з COVID-19 значно вищий, ніж у крові здорових людей. Рівень ApoВ та окисне-
них ЛПНЩ у крові вище у пацієнтів і з COVID-19 і з діабетом або ССЗ порівняно з пацієнтами з COVID-19
без супутніх захворювань. Таким чином, рівень ApoВ та окиснених ЛПНЩ може бути перспективним
маркером тяжкого COVID-19.
Ключові слова: COVID-19, діабет 2-го типу, серцево-судинні захворювання, аполіпопротеїн В, окиснені
ЛПНЩ.
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