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Article: Editorial: The interplay between oxidative stress, immune cells and inflammation in cardiovascular diseases.

Nosalski, R / Siedlinski, M / Neves, K B / Monaco, C

2024 Volume 11, Page(s) 1385809

Language	English
Publishing date	2024-02-27
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2781496-8
ISSN	2297-055X
ISSN	2297-055X
DOI	10.3389/fcvm.2024.1385809
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Article ; Online: Interplay Between Plasma Glycine and Branched-Chain Amino Acids Contributes to the Development of Hypertension and Coronary Heart Disease.

Dziedzic, Mateusz / Józefczuk, Ewelina / Guzik, Tomasz J / Siedlinski, Mateusz

Hypertension (Dallas, Tex. : 1979)

2024

Abstract: Background: Higher levels of plasma glycine are linked to a reduced risk, while increased levels of total branched-chain amino acids (tBCAAs) are associated with a higher risk of essential hypertension (HTN) and coronary heart disease (CHD). As these ... ...

Abstract	Background: Higher levels of plasma glycine are linked to a reduced risk, while increased levels of total branched-chain amino acids (tBCAAs) are associated with a higher risk of essential hypertension (HTN) and coronary heart disease (CHD). As these metabolic components are interconnected, analyzing the tBCAAs/glycine ratio may help to understand their interplay in the pathogenesis of cardiovascular disease. Methods: The Cox regression approach was combined with the development of novel genetic tools for assessments of associations between plasma metabolomic data (glycine, tBCAAs, and tBCAAs/glycine ratio) from the UK Biobank and the development of hypertension and CHD. Genome-wide association study was performed on 186 523 White UK Biobank participants to identify new independent genetic instruments for the 2-sample Mendelian randomization analyses. Results: The tBCAAs/glycine ratio was prospectively associated with a higher risk of developing hypertension and CHD (hazard ratio quintile, Q5 versus Q1, 1.196 [95% CI, 1.109-1.289] and 1.1226 [95% CI, 1.160-1.1296], respectively). Mendelian randomization analysis demonstrated that tBCAAs/glycine ratio ( Conclusions: The total BCAAs/glycine ratio is a key element of the metabolic signature contributing to hypertension and CHD, which may reflect biological pathways shared by glycine and tBCAAs.
Language	English
Publishing date	2024-04-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	423736-5
ISSN	1524-4563 ; 0194-911X ; 0362-4323
ISSN (online)	1524-4563
ISSN	0194-911X ; 0362-4323
DOI	10.1161/HYPERTENSIONAHA.123.22649
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Zs.A 1488: Show issues

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Article ; Online: Novel biomarkers and emerging tools to identify causal molecular pathways in hypertension and associated cardiovascular diseases.

Józefczuk, Ewelina / Guzik, Tomasz J / Siedlinski, Mateusz

Kardiologia polska

2023 Volume 81, Issue 3, Page(s) 221–231

Abstract: Hypertension (HT) is a modifiable risk factor for life-threatening cardiovascular diseases (CVDs) including coronary artery disease, heart failure, or stroke. Despite significant progress in understanding the pathophysiological mechanisms of the disease, ...

Abstract	Hypertension (HT) is a modifiable risk factor for life-threatening cardiovascular diseases (CVDs) including coronary artery disease, heart failure, or stroke. Despite significant progress in understanding the pathophysiological mechanisms of the disease, the molecular pathways targeted by HT treatment remain largely unchanged. This warrants the need for finding novel biomarkers, which are causally related to persistent high blood pressure (BP) and may be pharmacologically targeted. Analytical output derived from large-scale biobanks, containing high-throughput genetic and biochemical data, such as OLINK and SomaScan-based proteomics or Nuclear Magnetic Resonance-based metabolomics, as well as novel analytical tools including the Mendelian randomization (MR) approach, enabling genetic causal inference, may create new treatment opportunities for HT and related CVDs. MR analysis may constitute additional evidence for observational studies and facilitate selection of drug targets for clinical testing and has been already used to nominate potentially causal biomarkers for HT and CVDs such as circulating glycine, branched-chain amino acids, lipoprotein(a), insulin-like growth factor 1, or fibronectin 1. Using the MR framework, genetic proxies for targets of already known drugs, such as statins, PCSK9, and ACE inhibitors, may additionally be informative about potential side effects and eventually contribute to more personalized medicine. Finally, genetic causal inference may disentangle independent direct effects of correlated traits such as lipid classes or markers of inflammation on cardiovascular clinical outcomes such as atherosclerosis and HT. While several novel HT-targeting drugs are currently under clinical investigation (e.g. brain renin-angiotensin-aldosterone system inhibitors or endothelin-1 receptor antagonists), analysis of high-throughput proteomic and metabolomic data from well-powered studies may deliver novel druggable molecular targets for HT and associated CVDs.
MeSH term(s)	Humans ; Cardiovascular Diseases/genetics ; Proprotein Convertase 9 ; Proteomics ; Hypertension/drug therapy ; Hypertension/genetics ; Biomarkers
Chemical Substances	PCSK9 protein, human (EC 3.4.21.-) ; Proprotein Convertase 9 (EC 3.4.21.-) ; Biomarkers
Language	English
Publishing date	2023-02-05
Publishing country	Poland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	411492-9
ISSN	1897-4279 ; 0022-9032
ISSN (online)	1897-4279
ISSN	0022-9032
DOI	10.33963/KP.a2023.0037
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Zs.MO 474: Show issues

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Article ; Online: Immunology in COPD and the use of combustible cigarettes and heated tobacco products.

Błach, Justyna / Siedliński, Mateusz / Sydor, Wojciech

European journal of medical research

2023 Volume 28, Issue 1, Page(s) 397

Abstract: Chronic obstructive pulmonary disease (COPD) is one of the most common chronic respiratory diseases, characterised by high morbidity and mortality. COPD is characterised by a progressive decline of lung function caused by chronic inflammatory reactions ... ...

Abstract	Chronic obstructive pulmonary disease (COPD) is one of the most common chronic respiratory diseases, characterised by high morbidity and mortality. COPD is characterised by a progressive decline of lung function caused by chronic inflammatory reactions in the lung tissue due to continual exposure to harmful molecules by inhalation. As prevention plays a very important role in COPD, quitting smoking is the most important factor in reducing the decline in lung function. Unfortunately, many people are unable to break their nicotine addiction. This paper summarises current knowledge about combustible cigarettes (CSs) and alternative tobacco products such as heated tobacco products (HTPs) in COPD. The paper focuses on the immunological aspects of COPD and the influence of tobacco products on lung tissue immunology. There are differences in research results between HTPs and CSs in favour of HTPs. More long-term studies are needed to look at the effects of HTPs, especially in COPD. However, there is no doubt that it would be best for patients to give up their nicotine addiction completely.
MeSH term(s)	Humans ; Tobacco Use Disorder ; Tobacco Products/adverse effects ; Smoking/adverse effects ; Pulmonary Disease, Chronic Obstructive
Language	English
Publishing date	2023-10-04
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1329381-3
ISSN	2047-783X ; 0949-2321
ISSN (online)	2047-783X
ISSN	0949-2321
DOI	10.1186/s40001-023-01374-2
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Article ; Online: Significance of sphingosine-1-phosphate in cardiovascular physiology and pathology.

Jozefczuk, E / Guzik, T J / Siedlinski, M

Pharmacological research

2020 Volume 156, Page(s) 104793

Abstract: Sphingosine-1-phosphate (S1P) is a signaling lipid, synthetized by sphingosine kinases (SPHK1 and SPHK2), that affects cardiovascular function in various ways. S1P signaling is complex, particularly since its molecular action is reliant on the ... ...

Abstract	Sphingosine-1-phosphate (S1P) is a signaling lipid, synthetized by sphingosine kinases (SPHK1 and SPHK2), that affects cardiovascular function in various ways. S1P signaling is complex, particularly since its molecular action is reliant on the differential expression of its receptors (S1PR1, S1PR2, S1PR3, S1PR4, S1PR5) within various tissues. Significance of this sphingolipid is manifested early in vertebrate development as certain defects in S1P signaling result in embryonic lethality due to defective vasculo- or cardiogenesis. Similar in the mature organism, S1P orchestrates both physiological and pathological processes occurring in the heart and vasculature of higher eukaryotes. S1P regulates cell fate, vascular tone, endothelial function and integrity as well as lymphocyte trafficking, thus disbalance in its production and signaling has been linked with development of such pathologies as arterial hypertension, atherosclerosis, endothelial dysfunction and aberrant angiogenesis. Number of signaling mechanisms are critical - from endothelial nitric oxide synthase through STAT3, MAPK and Akt pathways to HDL particles involved in redox and inflammatory balance. Moreover, S1P controls both acute cardiac responses (cardiac inotropy and chronotropy), as well as chronic processes (such as apoptosis and hypertrophy), hence numerous studies demonstrate significance of S1P in the pathogenesis of hypertrophic/fibrotic heart disease, myocardial infarction and heart failure. This review presents current knowledge concerning the role of S1P in the cardiovascular system, as well as potential therapeutic approaches to target S1P signaling in cardiovascular diseases.
MeSH term(s)	Animals ; Cardiovascular Diseases/metabolism ; Cardiovascular Diseases/pathology ; Cardiovascular Diseases/physiopathology ; Cardiovascular System/embryology ; Cardiovascular System/metabolism ; Cardiovascular System/physiopathology ; Embryonic Development ; Hemodynamics ; Humans ; Lysophospholipids/metabolism ; Neovascularization, Physiologic ; Receptors, Lysosphingolipid/metabolism ; Signal Transduction ; Sphingosine/analogs & derivatives ; Sphingosine/metabolism
Chemical Substances	Lysophospholipids ; Receptors, Lysosphingolipid ; sphingosine 1-phosphate (26993-30-6) ; Sphingosine (NGZ37HRE42)
Language	English
Publishing date	2020-04-08
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1003347-6
ISSN	1096-1186 ; 0031-6989 ; 1043-6618
ISSN (online)	1096-1186
ISSN	0031-6989 ; 1043-6618
DOI	10.1016/j.phrs.2020.104793
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Zs.A 721: Show issues

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Article ; Online: Systemic and vascular inflammation in experimental allergic asthma.

Konior-Rozlachowska, A / Siedlinski, M / Szczepaniak, P / Nosalski, R / Murray, E / Mikolajczyk, T P

Journal of physiology and pharmacology : an official journal of the Polish Physiological Society

2021 Volume 72, Issue 2

Abstract: Allergic asthma and atherosclerosis are inflammatory diseases characterized by similar sets of circulating inflammatory cells, in addition to mast cells in the airway and vessel wall. Animal models and human studies provide evidence of a potential ... ...

Abstract	Allergic asthma and atherosclerosis are inflammatory diseases characterized by similar sets of circulating inflammatory cells, in addition to mast cells in the airway and vessel wall. Animal models and human studies provide evidence of a potential interaction between the two apparently unrelated diseases. The main objective of this study was to determine whether experimental allergic asthma is accompanied by inflammatory responses, measured as the activation of the vasculature and the presence of immune cells in the perivascular adipose tissue. For this purpose, male Dunkin Hartley guinea pigs weighing 250 - 300 g were sensitized twice with 10 μg ovalbumin dissolved in aluminium hydroxide (Al(OH)
MeSH term(s)	Allergens ; Animals ; Asthma ; Bronchoalveolar Lavage Fluid ; Disease Models, Animal ; Guinea Pigs ; Inflammation ; Male ; Ovalbumin
Chemical Substances	Allergens ; Ovalbumin (9006-59-1)
Language	English
Publishing date	2021-08-06
Publishing country	Poland
Document type	Journal Article
ZDB-ID	1125221-2
ISSN	1899-1505 ; 0867-5910 ; 0044-6033
ISSN (online)	1899-1505
ISSN	0867-5910 ; 0044-6033
DOI	10.26402/jpp.2021.2.03
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Article ; Online: Response by Siedlinski et al to Letters Regarding Article, "White Blood Cells and Blood Pressure: A Mendelian Randomization Study".

Siedlinski, Mateusz / Holmes, Michael V / Guzik, Tomasz J

Circulation

2020 Volume 142, Issue 13, Page(s) e191–e192

MeSH term(s)	Blood Pressure ; Leukocyte Count ; Leukocytes ; Mendelian Randomization Analysis
Language	English
Publishing date	2020-09-28
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	80099-5
ISSN	1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
ISSN (online)	1524-4539
ISSN	0009-7322 ; 0069-4193 ; 0065-8499
DOI	10.1161/CIRCULATIONAHA.120.049870
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Article ; Online: E-vaporating benefits of e-vaping.

Siedlinski, Mateusz / Harrison, David G / Guzik, Tomasz J

European heart journal

2020 Volume 41, Issue 26, Page(s) 2484–2486

MeSH term(s)	Brain ; E-Cigarette Vapor ; Electronic Nicotine Delivery Systems ; Humans ; NADPH Oxidases ; Oxidative Stress ; Vaping
Chemical Substances	E-Cigarette Vapor ; NADPH Oxidases (EC 1.6.3.-)
Language	English
Publishing date	2020-01-16
Publishing country	England
Document type	Editorial ; Comment
ZDB-ID	603098-1
ISSN	1522-9645 ; 0195-668X
ISSN (online)	1522-9645
ISSN	0195-668X
DOI	10.1093/eurheartj/ehz875
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Zs.A 1563: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 640: Show issues

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Article ; Online: Silencing of

Jozefczuk, Ewelina / Szczepaniak, Piotr / Guzik, Tomasz Jan / Siedlinski, Mateusz

International journal of molecular sciences

2021 Volume 22, Issue 7

Abstract: Sphingosine kinase-1 (Sphk1) and its product, sphingosine-1-phosphate (S1P) are important regulators of cardiac growth and function. Numerous studies have reported that Sphk1/S1P signaling is essential for embryonic cardiac development and promotes ... ...

Abstract	Sphingosine kinase-1 (Sphk1) and its product, sphingosine-1-phosphate (S1P) are important regulators of cardiac growth and function. Numerous studies have reported that Sphk1/S1P signaling is essential for embryonic cardiac development and promotes pathological cardiac hypertrophy in adulthood. However, no studies have addressed the role of Sphk1 in postnatal cardiomyocyte (CM) development so far. The present study aimed to assess the molecular mechanism(s) by which
MeSH term(s)	Animals ; Animals, Newborn/metabolism ; Cell Differentiation/physiology ; Cell Proliferation/drug effects ; Lysophospholipids/metabolism ; Mice ; Mice, Inbred C57BL ; Myocytes, Cardiac/metabolism ; Myocytes, Cardiac/physiology ; Phosphotransferases (Alcohol Group Acceptor)/genetics ; Phosphotransferases (Alcohol Group Acceptor)/metabolism ; RNA, Small Interfering/pharmacology ; Receptors, Lysosphingolipid/metabolism ; Signal Transduction/drug effects ; Sphingosine/analogs & derivatives ; Sphingosine/metabolism
Chemical Substances	Lysophospholipids ; RNA, Small Interfering ; Receptors, Lysosphingolipid ; sphingosine 1-phosphate (26993-30-6) ; Phosphotransferases (Alcohol Group Acceptor) (EC 2.7.1.-) ; Sphk1 protein, mouse (EC 2.7.1.-) ; sphingosine kinase (EC 2.7.1.-) ; Sphingosine (NGZ37HRE42)
Language	English
Publishing date	2021-03-31
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/ijms22073616
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Article ; Online: Nox1/4 inhibition exacerbates age dependent perivascular inflammation and fibrosis in a model of spontaneous hypertension.

Nosalski, R / Mikolajczyk, T / Siedlinski, M / Saju, B / Koziol, J / Maffia, P / Guzik, T J

Pharmacological research

2020 Volume 161, Page(s) 105235

Abstract: Hypertension is associated with oxidative stress and perivascular inflammation, critical contributors to perivascular fibrosis and accelerated vascular ageing. Oxidative stress can promote vascular inflammation, creating options for potential use of ... ...

Abstract	Hypertension is associated with oxidative stress and perivascular inflammation, critical contributors to perivascular fibrosis and accelerated vascular ageing. Oxidative stress can promote vascular inflammation, creating options for potential use of NADPH oxidase inhibitors in pharmacological targeting of perivascular inflammation and its consequences. Accordingly, we characterized age-related changes in oxidative stress and immune cell infiltration in normotensive (WKY) and spontaneously hypertensive rats (SHRs). Subsequently, we used pharmacological inhibitors of Nox1 (ML171) and Nox1/Nox4 (GKT137831; 60 mg/kg), to modulate NADPH oxidase activity at the early stage of spontaneous hypertension and investigated their effects on perivascular inflammation and fibrosis. RESULTS: Ageing was associated with a progressive increase of blood pressure as well as an elevation of the total number of leukocytes, macrophages and NK cells infiltrating perivascular adipose tissue (PVAT) in SHRs but not in WKY. At 1 month of age, when blood pressure was not yet different, only perivascular NK cells were significantly higher in SHR. Spontaneous hypertension was also accompanied by the higher perivascular T cell accumulation, although this increase was age independent. Aortic Nox1 and Nox2 mRNA expression increased with age only in SHR but not in WKY, while age-related increase of Nox4 mRNA in the vessels has been observed in both groups, it was more pronounced in SHRs. At early stage of hypertension (3-months) the most pronounced differences were observed in Nox1 and Nox4. Surprisingly, GKT137831, dual inhibitor of Nox1/4, therapy increased both blood pressure and perivascular macrophage infiltration. Mechanistically, this was linked to increased expression of proinflammatory chemokines expression (CCL2 and CCL5) in PVAT. This inflammatory response translated to increased perivascular fibrosis. This effect was likely Nox4 dependent as the Nox1 inhibitor ML171 did not affect the development of spontaneous hypertension, perivascular macrophage accumulation, chemokine expression nor adventitial collagen deposition. In summary, spontaneous hypertension promotes ageing-associated perivascular inflammation which is exacerbated by Nox4 but not Nox1 pharmacological inhibition.
MeSH term(s)	Adipose Tissue/drug effects ; Adipose Tissue/enzymology ; Adipose Tissue/immunology ; Adipose Tissue/pathology ; Age Factors ; Animals ; Aorta/drug effects ; Aorta/enzymology ; Aorta/immunology ; Aorta/pathology ; Blood Pressure ; Disease Models, Animal ; Enzyme Inhibitors/toxicity ; Fibrosis ; Hypertension/complications ; Hypertension/physiopathology ; Inflammation Mediators/metabolism ; Killer Cells, Natural/drug effects ; Killer Cells, Natural/immunology ; Killer Cells, Natural/metabolism ; Macrophages/drug effects ; Macrophages/immunology ; Macrophages/metabolism ; Male ; NADPH Oxidase 1/antagonists & inhibitors ; NADPH Oxidase 1/metabolism ; NADPH Oxidase 4/antagonists & inhibitors ; NADPH Oxidase 4/metabolism ; Pyrazolones/toxicity ; Pyridones/toxicity ; Rats, Inbred SHR ; Rats, Inbred WKY ; Signal Transduction ; T-Lymphocytes/drug effects ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Vasculitis/chemically induced ; Vasculitis/enzymology ; Vasculitis/immunology ; Vasculitis/pathology
Chemical Substances	Enzyme Inhibitors ; Inflammation Mediators ; Pyrazolones ; Pyridones ; setanaxib (45II35329V) ; NADPH Oxidase 1 (EC 1.6.3.-) ; NADPH Oxidase 4 (EC 1.6.3.-) ; NOX1 protein, rat (EC 1.6.3.-) ; Nox4 protein, rat (EC 1.6.3.-)
Language	English
Publishing date	2020-10-22
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1003347-6
ISSN	1096-1186 ; 0031-6989 ; 1043-6618
ISSN (online)	1096-1186
ISSN	0031-6989 ; 1043-6618
DOI	10.1016/j.phrs.2020.105235
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