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Article ; Online: Nicotinamide adenine dinucleotide fluorescence to assess microvascular disturbances in post-COVID-19 patients.

Romanowska-Kocejko, Marzena / Dudziak, Maria / Hellmann, Marcin

2021 Volume 29, Issue 1, Page(s) 154–156

MeSH term(s)	COVID-19 ; Fluorescence ; Humans ; NAD ; SARS-CoV-2
Chemical Substances	NAD (0U46U6E8UK)
Language	English
Publishing date	2021-10-21
Publishing country	Poland
Document type	Journal Article
ZDB-ID	2488680-4
ISSN	1898-018X ; 1897-5593
ISSN (online)	1898-018X
ISSN	1897-5593
DOI	10.5603/CJ.a2021.0132
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Article ; Online: Subtle microvascular endothelial impairment in a young patient recovered from mild COVID-19.

Hellmann, Marcin / Romanowska-Kocejko, Marzena / Żarczyńska-Buchowiecka, Marta / Dudziak, Maria

Polish archives of internal medicine

2021 Volume 131, Issue 6, Page(s) 561–562

MeSH term(s)	COVID-19 ; Humans ; SARS-CoV-2
Language	English
Publishing date	2021-04-14
Publishing country	Poland
Document type	Journal Article
ZDB-ID	123500-x
ISSN	1897-9483 ; 0032-3772
ISSN (online)	1897-9483
ISSN	0032-3772
DOI	10.20452/pamw.15938
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Article: Red Blood Cell Adenylate Energetics Is Related to Endothelial and Microvascular Function in Long COVID.

Romanowska-Kocejko, Marzena / Jędrzejewska, Agata / Braczko, Alicja / Stawarska, Klaudia / Król, Oliwia / Frańczak, Marika / Harasim, Gabriela / Smoleński, Ryszard T / Hellmann, Marcin / Kutryb-Zając, Barbara

Biomedicines

2024 Volume 12, Issue 3

Abstract: Adenine nucleotides play a critical role in maintaining essential functions of red blood cells (RBCs), including energy metabolism, redox status, shape fluctuations and RBC-dependent endothelial and microvascular functions. Recently, it has been shown ... ...

Abstract	Adenine nucleotides play a critical role in maintaining essential functions of red blood cells (RBCs), including energy metabolism, redox status, shape fluctuations and RBC-dependent endothelial and microvascular functions. Recently, it has been shown that infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) might lead to morphological and metabolic alterations in erythrocytes in both mild and severe cases of coronavirus disease (COVID-19). However, little is known about the effects of COVID-19 on the nucleotide energetics of RBCs nor about the potential contribution of nucleotide metabolism to the long COVID syndrome. This study aimed to analyze the levels of adenine nucleotides in RBCs isolated from patients 12 weeks after mild SARS-CoV-2 infection who suffered from long COVID symptoms and to relate them with the endothelial and microvascular function parameters as well as the rate of peripheral tissue oxygen supply. Although the absolute quantities of adenine nucleotides in RBCs were rather slightly changed in long COVID individuals, many parameters related to the endothelial and microcirculatory function showed significant correlations with RBC adenosine triphosphate (ATP) and total adenine nucleotide (TAN) concentration. A particularly strong relationship was observed between ATP in RBCs and the serum ratio of arginine to asymmetric dimethylarginine-an indicator of endothelial function. Consistently, a positive correlation was also observed between the ATP/ADP ratio and diminished reactive hyperemic response in long COVID patients, assessed by the flow-mediated skin fluorescence (FMSF) technique, which reflected decreased vascular nitric oxide bioavailability. In addition, we have shown that patients after COVID-19 have significantly impaired ischemic response parameters (IR max and IR index), examined by FMSF, which revealed diminished residual bioavailability of oxygen in epidermal keratinocytes after brachial artery occlusion. These ischemic response parameters revealed a strong positive correlation with the RBC ATP/ADP ratio, confirming a key role of RBC bioenergetics in peripheral tissue oxygen supply. Taken together, the outcomes of this study indicate that dysregulation of metabolic processes in erythrocytes with the co-occurring endothelial and microvascular dysfunction is associated with diminished intracellular oxygen delivery, which may partly explain long COVID-specific symptoms such as physical impairment and fatigue.
Language	English
Publishing date	2024-03-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines12030554
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Article ; Online: Sacubitril/valsartan improved microvascular endothelial function in a young patient with COVID-19-related mild left ventricular dysfunction.

Hellmann, Marcin / Dąbrowska, Edyta / Żarczyńska-Buchowiecka, Marta / Romanowska-Kocejko, Marzena / Narkiewicz, Krzysztof / Gruchała, Marcin / Dudziak, Maria

Kardiologia polska

2022 Volume 80, Issue 5, Page(s) 614–615

Language	English
Publishing date	2022-03-02
Publishing country	Poland
Document type	Journal Article
ZDB-ID	411492-9
ISSN	1897-4279 ; 0022-9032
ISSN (online)	1897-4279
ISSN	0022-9032
DOI	10.33963/KP.a2022.0063
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Article ; Online: Changes in Adenosine Deaminase Activity and Endothelial Dysfunction after Mild Coronavirus Disease-2019.

Jedrzejewska, Agata / Kawecka, Ada / Braczko, Alicja / Romanowska-Kocejko, Marzena / Stawarska, Klaudia / Deptuła, Milena / Zawrzykraj, Małgorzata / Franczak, Marika / Krol, Oliwia / Harasim, Gabriela / Walczak, Iga / Pikuła, Michał / Hellmann, Marcin / Kutryb-Zając, Barbara

International journal of molecular sciences

2023 Volume 24, Issue 17

Abstract: Endothelial cells are a preferential target for SARS-CoV-2 infection. Previously, we have reported that vascular adenosine deaminase 1 (ADA1) may serve as a biomarker of endothelial activation and vascular inflammation, while ADA2 plays a critical role ... ...

Abstract	Endothelial cells are a preferential target for SARS-CoV-2 infection. Previously, we have reported that vascular adenosine deaminase 1 (ADA1) may serve as a biomarker of endothelial activation and vascular inflammation, while ADA2 plays a critical role in monocyte and macrophage function. In this study, we investigated the activities of circulating ADA isoenzymes in patients 8 weeks after mild COVID-19 and related them to the parameters of inflammation and microvascular/endothelial function. Post-COVID patients revealed microvascular dysfunction associated with the changes in circulating parameters of endothelial dysfunction and inflammatory activation. Interestingly, serum total ADA and ADA2 activities were diminished in post-COVID patients, while ADA1 remained unchanged in comparison to healthy controls without a prior diagnosis of SARS-CoV-2 infection. While serum ADA1 activity tended to positively correspond with the parameters of endothelial activation and inflammation, sICAM-1 and TNFα, serum ADA2 activity correlated with IL-10. Simultaneously, post-COVID patients had lower circulating levels of ADA1-anchoring protein, CD26, that may serve as an alternative receptor for virus binding. This suggests that after the infection CD26 is rather maintained in cell-attached form, enabling ADA1 complexing. This study points to the possible role of ADA isoenzymes in cardiovascular complications after mild COVID-19.
MeSH term(s)	Humans ; Adenosine Deaminase ; COVID-19/metabolism ; Dipeptidyl Peptidase 4 ; Endothelial Cells ; Inflammation ; Isoenzymes ; SARS-CoV-2 ; Vascular Diseases
Chemical Substances	Adenosine Deaminase (EC 3.5.4.4) ; Dipeptidyl Peptidase 4 (EC 3.4.14.5) ; Isoenzymes ; ADA2 protein, human (EC 3.5.4.4)
Language	English
Publishing date	2023-08-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241713140
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Article ; Online: Effectiveness and safety of PCSK9 inhibitor therapy in patients with familial hypercholesterolemia within a therapeutic program in Poland: Preliminary multicenter data.

Chlebus, Krzysztof / Cybulska, Barbara / Dobrowolski, Piotr / Romanowska-Kocejko, Marzena / Żarczyńska-Buchowiecka, Marta / Gilis-Malinowska, Natasza / Stróżyk, Aneta / Borowiec-Wolna, Justyna / Pajkowski, Marcin / Bobrowska, Beata / Rajtar-Salwa, Renata / Kwapiszewska, Aleksandra / Waluś-Miarka, Małgorzata / Chmara, Magdalena / Gałąska, Rafał / Małecki, Maciej / Zdrojewski, Tomasz / Gruchała, Marcin

Cardiology journal

2022 Volume 29, Issue 1, Page(s) 62–71

Abstract: Background: In Poland, treatment with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors has become available free of charge in a therapeutic program. Assessed herein, is the efficacy and safety of alirocumab and evolocumab in patients ... ...

Abstract	Background: In Poland, treatment with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors has become available free of charge in a therapeutic program. Assessed herein, is the efficacy and safety of alirocumab and evolocumab in patients with heterozygous familial hypercholesterolemia (FH). Methods: Data of 55 adult FH patients who participated in the program were analyzed upon meeting the criteria established by the Ministry of Health (low density lipoprotein cholesterol [LDL-C] above 160 mg/dL on max. tolerated statin dose and ezetimib). The efficacy of PCSK9 inhibitors in reducing LDL-C with drug administration every 2 weeks was assessed after 3 months and 1 year of therapy. A safety profile evaluation was performed at each visit. 48 patients completed the 3-month and 21 for the 1-year observation periods (34 patients treated with alirokumab and 14 with evolocumab). Results: The mean concentration of direct-measured LDL-C decreased from the initial level of 215.1 ± 74.5 mg/dL to 75.3 ± 64.1 mg/dL, i.e., by 65 ± 14% following 3 months of treatment. This effect was stable in 1-year observation (77.7 ± 72.8 mg/dL). Adverse effects were flu-like symptoms (13.0%), injection site reactions (11.1%), fatigue (5.6%) and musculoskeletal symptoms (5.6%). Seven patients failed to complete the 3-month treatment period due to side effects or non-compliance, and 1 patient failed to complete the 1-year treatment due to myalgia. Conclusions: This study confirmed high effectiveness of PCSK9 inhibitors in reducing LDL-C levels in patients with FH. Due to restrictive inclusion criteria with LDL-C threshold level > 160 mg/dL (> 4.1 mmol/L) required for participation in the therapeutic program, a relatively small number of FH patients were eligible for treatment.
MeSH term(s)	Adult ; Antibodies, Monoclonal/adverse effects ; Cholesterol, LDL ; Humans ; Hyperlipoproteinemia Type II/diagnosis ; Hyperlipoproteinemia Type II/drug therapy ; PCSK9 Inhibitors ; Poland ; Proprotein Convertase 9 ; Treatment Outcome
Chemical Substances	Antibodies, Monoclonal ; Cholesterol, LDL ; PCSK9 Inhibitors ; PCSK9 protein, human (EC 3.4.21.-) ; Proprotein Convertase 9 (EC 3.4.21.-)
Language	English
Publishing date	2022-02-11
Publishing country	Poland
Document type	Journal Article ; Multicenter Study
ZDB-ID	2488680-4
ISSN	1898-018X ; 1897-5593
ISSN (online)	1898-018X
ISSN	1897-5593
DOI	10.5603/CJ.a2022.0003
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Article: Noninvasive assessment of endothelial function and vascular parameters in patients with familial and nonfamilial hypercholesterolemia.

Lewandowski, Paweł / Romanowska-Kocejko, Marzena / Węgrzyn, Agnieszka / Chmara, Magdalena / Żuk, Monika / Limon, Janusz / Wasąg, Bartosz / Rynkiewicz, Andrzej / Gruchała, Marcin

Polskie Archiwum Medycyny Wewnetrznej

2014 Volume 124, Issue 10, Page(s) 516–524

Abstract: Introduction: Endothelial dysfunction is one of the markers of atherosclerosis.: Objectives: The aim of the study was to evaluate endothelial function by assessing flow-mediated dilation (FMD) and to measure the parameters of brachial arterial ... ...

Abstract	Introduction: Endothelial dysfunction is one of the markers of atherosclerosis. Objectives: The aim of the study was to evaluate endothelial function by assessing flow-mediated dilation (FMD) and to measure the parameters of brachial arterial stiffness in patients with familial hypercholesterolemia (FH) and those with high low-density lipoprotein (LDL) cholesterol levels without FH mutations (nonfamilial hypercholesterolemia - non-FH). Patients and methods: The study involved 60 patients (mean age, 41.9 ±7.7 y) without documented cardiovascular events and clinical symptoms of cardiovascular diseases: 21 patients with elevated plasma LDL cholesterol levels and genetically confirmed FH, 19 patients with elevated LDL cholesterol levels and without FH mutations, and 20 healthy controls. In each patient, ultrasound imaging was used to assess endothelium-dependent FMD and nitroglycerin-induced endothelium-independent dilation (EID) in the brachial artery. In addition, echo-tracking and photoplethysmography were used to assess the parameters of arterial stiffness. Results: FMD was significantly lower in patients with FH (11.0% ±9.9% vs. 21.0% ±14.3%, P <0.01) and non-FH (14.2% ±10.1% vs. 21.0% ±14.3%, P <0.05) compared with controls. EID and arterial stiffness parameters were similar between the groups. Conclusions: Reduced FMD may suggest endothelial dysfunction. A lack of significant differences in arterial stiffness parameters may indicate that vascular remodeling is not advanced in patients with elevated LDL cholesterol levels. A lack of significant differences in FMD and arterial stiffness between patients with and without FH may indicate that FH mutation itself is not the main determinant of endothelial dysfunction and vascular remodeling in younger patients with hypercholesterolemia.
MeSH term(s)	Adult ; Brachial Artery/diagnostic imaging ; Brachial Artery/physiopathology ; Carotid Artery, Common/diagnostic imaging ; Carotid Artery, Common/physiopathology ; Case-Control Studies ; Cholesterol, LDL/blood ; Endothelium, Vascular/physiopathology ; Female ; Humans ; Hypercholesterolemia/diagnostic imaging ; Hypercholesterolemia/physiopathology ; Hyperlipoproteinemia Type II/diagnostic imaging ; Hyperlipoproteinemia Type II/physiopathology ; Male ; Middle Aged
Chemical Substances	Cholesterol, LDL
Language	English
Publishing date	2014-09-03
Publishing country	Poland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	123500-x
ISSN	1897-9483 ; 0032-3772
ISSN (online)	1897-9483
ISSN	0032-3772
DOI	10.20452/pamw.2458
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Article ; Online: Cardiovascular risk factor profiles in familial hypercholesterolemia patients with and without genetic mutation compared to a nationally representative sample of adults in a high-risk European country.

Chlebus, Krzysztof / Zdrojewski, Tomasz / Gruchała, Marcin / Gałąska, Rafał / Pajkowski, Marcin / Kocejko, Marzena Romanowska- / Chmara, Magdalena / Pencina, Michael J

American heart journal

2019 Volume 218, Page(s) 32–45

Abstract: Background: There is a paucity of data on the distribution of cardiovascular risk factors in patients with familial hypercholesterolemia (FH) as compared to the general population. The aim of the study was to compare cardiovascular risk factors in a ... ...

Abstract	Background: There is a paucity of data on the distribution of cardiovascular risk factors in patients with familial hypercholesterolemia (FH) as compared to the general population. The aim of the study was to compare cardiovascular risk factors in a cohort of FH patients to the representative sample of adults in Poland who represent a high-cardiovascular risk European region. Methods: We compared the distribution of risk factors in 1,382 individuals with FH phenotype referred for genetic testing between 2006 and 2014 to the National Centre of Familial Hypercholesterolemia in Gdansk, Poland. The cohort was comprised of 637 positive FH(+) and 745 negative FH(-) patients who were compared to a nationally representative sample of 2,413 adults age 18-79, standardized by age and sex, from the NATPOL 2011 study (NATPOL). We analyzed patients' distribution of history of atherosclerotic cardiovascular disease (ASCVD) and standard risk factors including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides, systolic and diastolic blood pressure (SBP, DBP), body mass index, smoking, and diabetes. Results: FH(+) patients (mean age 45.6 years) had the highest LDL-C of 241.7 mg/dL (95% CI 234.8-248.5) compared to 206.1 mg/dL (200.5-211.7) in FH(-) patients (mean age 48.2) and 126.2 mg/dL (124.8-127.6) in NATPOL. Mean SBP was the lowest in FH(+) patients at 128.7 mm Hg (126.7-130.7) compared to 133.4 mm Hg (132.6-134.3) in NATPOL and 134.4 mm Hg (132.3-136.5) in FH(-). No differences were found in the prevalence of diabetes and body mass index. Smoking was less common in FH(+) at 12.4% (9.4-15.4) compared to both FH(-) and NATPOL: 20.4% (16.6-24.1) and 28.4% (26.6-30.2), respectively. The prevalence of individuals with a history of ASCVD in both FH(+) and FH(-) was nearly 3-fold higher compared to NATPOL: 26% (21.8-30.1) and 26.6% (22.2-30.9) versus 9.5% (8.3-10.7), respectively. Conclusions: The FH(+) patients had significantly higher mean LDL-C, but the levels of nonlipid factors were lower or similar compared to the other groups. Both FH(+) and FH(-) were characterized by a heavy burden of ASCVD. This suggests that cholesterol, and no other risk factors, is a key contributor to cardiovascular risk in patients with FH, especially those with genetic mutation.
MeSH term(s)	Adult ; Aged ; Atherosclerosis/epidemiology ; Blood Pressure Determination ; Body Mass Index ; Cholesterol, HDL/blood ; Cholesterol, LDL/blood ; Cohort Studies ; Cross-Sectional Studies ; Diabetes Mellitus/epidemiology ; Female ; Genetic Testing ; Humans ; Hyperlipoproteinemia Type II/blood ; Hyperlipoproteinemia Type II/genetics ; Male ; Middle Aged ; Mutation ; Poland/epidemiology ; Prevalence ; Risk Factors ; Smoking/epidemiology ; Triglycerides/blood
Chemical Substances	Cholesterol, HDL ; Cholesterol, LDL ; Triglycerides
Language	English
Publishing date	2019-10-23
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80026-0
ISSN	1097-6744 ; 0002-8703
ISSN (online)	1097-6744
ISSN	0002-8703
DOI	10.1016/j.ahj.2019.09.007
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Article ; Online: Nicotinamide adenine dinucleotide fluorescence to assess microvascular disturbances in post-COVID-19 patients.

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Article ; Online: Subtle microvascular endothelial impairment in a young patient recovered from mild COVID-19.

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Article: Red Blood Cell Adenylate Energetics Is Related to Endothelial and Microvascular Function in Long COVID.

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Article ; Online: Sacubitril/valsartan improved microvascular endothelial function in a young patient with COVID-19-related mild left ventricular dysfunction.

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Article ; Online: Changes in Adenosine Deaminase Activity and Endothelial Dysfunction after Mild Coronavirus Disease-2019.

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Article ; Online: Effectiveness and safety of PCSK9 inhibitor therapy in patients with familial hypercholesterolemia within a therapeutic program in Poland: Preliminary multicenter data.

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Article: Noninvasive assessment of endothelial function and vascular parameters in patients with familial and nonfamilial hypercholesterolemia.

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Article ; Online: Cardiovascular risk factor profiles in familial hypercholesterolemia patients with and without genetic mutation compared to a nationally representative sample of adults in a high-risk European country.

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