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  1. Article: The Causal Relationship between Endothelin-1 and Hypertension: Focusing on Endothelial Dysfunction, Arterial Stiffness, Vascular Remodeling, and Blood Pressure Regulation.

    Kostov, Krasimir

    Life (Basel, Switzerland)

    2021  Volume 11, Issue 9

    Abstract: Hypertension (HTN) is one of the most prevalent diseases worldwide and is among the most important risk factors for cardiovascular and cerebrovascular complications. It is currently thought to be the result of disturbances in a number of neural, renal, ... ...

    Abstract Hypertension (HTN) is one of the most prevalent diseases worldwide and is among the most important risk factors for cardiovascular and cerebrovascular complications. It is currently thought to be the result of disturbances in a number of neural, renal, hormonal, and vascular mechanisms regulating blood pressure (BP), so crucial importance is given to the imbalance of a number of vasoactive factors produced by the endothelium. Decreased nitric oxide production and increased production of endothelin-1 (ET-1) in the vascular wall may promote oxidative stress and low-grade inflammation, with the development of endothelial dysfunction (ED) and increased vasoconstrictor activity. Increased ET-1 production can contribute to arterial aging and the development of atherosclerotic changes, which are associated with increased arterial stiffness and manifestation of isolated systolic HTN. In addition, ET-1 is involved in the complex regulation of BP through synergistic interactions with angiotensin II, regulates the production of catecholamines and sympathetic activity, affects renal hemodynamics and water-salt balance, and regulates baroreceptor activity and myocardial contractility. This review focuses on the relationship between ET-1 and HTN and in particular on the key role of ET-1 in the pathogenesis of ED, arterial structural changes, and impaired vascular regulation of BP. The information presented includes basic concepts on the role of ET-1 in the pathogenesis of HTN without going into detailed analyses, which allows it to be used by a wide range of specialists. Also, the main pathological processes and mechanisms are richly illustrated for better understanding.
    Language English
    Publishing date 2021-09-20
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2662250-6
    ISSN 2075-1729
    ISSN 2075-1729
    DOI 10.3390/life11090986
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The Causal Relationship between Endothelin-1 and Hypertension

    Krasimir Kostov

    Life, Vol 11, Iss 986, p

    Focusing on Endothelial Dysfunction, Arterial Stiffness, Vascular Remodeling, and Blood Pressure Regulation

    2021  Volume 986

    Abstract: Hypertension (HTN) is one of the most prevalent diseases worldwide and is among the most important risk factors for cardiovascular and cerebrovascular complications. It is currently thought to be the result of disturbances in a number of neural, renal, ... ...

    Abstract Hypertension (HTN) is one of the most prevalent diseases worldwide and is among the most important risk factors for cardiovascular and cerebrovascular complications. It is currently thought to be the result of disturbances in a number of neural, renal, hormonal, and vascular mechanisms regulating blood pressure (BP), so crucial importance is given to the imbalance of a number of vasoactive factors produced by the endothelium. Decreased nitric oxide production and increased production of endothelin-1 (ET-1) in the vascular wall may promote oxidative stress and low-grade inflammation, with the development of endothelial dysfunction (ED) and increased vasoconstrictor activity. Increased ET-1 production can contribute to arterial aging and the development of atherosclerotic changes, which are associated with increased arterial stiffness and manifestation of isolated systolic HTN. In addition, ET-1 is involved in the complex regulation of BP through synergistic interactions with angiotensin II, regulates the production of catecholamines and sympathetic activity, affects renal hemodynamics and water–salt balance, and regulates baroreceptor activity and myocardial contractility. This review focuses on the relationship between ET-1 and HTN and in particular on the key role of ET-1 in the pathogenesis of ED, arterial structural changes, and impaired vascular regulation of BP. The information presented includes basic concepts on the role of ET-1 in the pathogenesis of HTN without going into detailed analyses, which allows it to be used by a wide range of specialists. Also, the main pathological processes and mechanisms are richly illustrated for better understanding.
    Keywords endothelin-1 ; hypertension ; oxidative stress ; low-grade inflammation ; endothelial dysfunction ; arterial stiffness ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2021-09-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Effects of Magnesium Deficiency on Mechanisms of Insulin Resistance in Type 2 Diabetes: Focusing on the Processes of Insulin Secretion and Signaling.

    Kostov, Krasimir

    International journal of molecular sciences

    2019  Volume 20, Issue 6

    Abstract: Magnesium ( ... ...

    Abstract Magnesium (Mg
    MeSH term(s) Animals ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/pathology ; Humans ; Insulin Resistance ; Insulin Secretion ; Magnesium Deficiency/complications ; Magnesium Deficiency/pathology ; Models, Biological ; Signal Transduction
    Language English
    Publishing date 2019-03-18
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms20061351
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Effects of Magnesium Deficiency on Mechanisms of Insulin Resistance in Type 2 Diabetes

    Krasimir Kostov

    International Journal of Molecular Sciences, Vol 20, Iss 6, p

    Focusing on the Processes of Insulin Secretion and Signaling

    2019  Volume 1351

    Abstract: Magnesium (Mg2+) is an essential mineral for human health and plays an important role in the regulation of glucose homeostasis and insulin actions. Despite the widespread clinical evidences for the association of Mg2+ deficiency (MgD) and type 2 diabetes ...

    Abstract Magnesium (Mg2+) is an essential mineral for human health and plays an important role in the regulation of glucose homeostasis and insulin actions. Despite the widespread clinical evidences for the association of Mg2+ deficiency (MgD) and type 2 diabetes mellitus (T2D), molecular mechanisms by which Mg2+ contributes to insulin resistance (IR) are still under discussion. Mg2+ regulates electrical activity and insulin secretion in pancreatic beta-cells. Intracellular Mg2+ concentrations are critical for the phosphorylation of the insulin receptor and other downstream signal kinases of the target cells. Low Mg2+ levels result in a defective tyrosine kinase activity, post-receptor impairment in insulin action, altered cellular glucose transport, and decreased cellular glucose utilization, which promotes peripheral IR in T2D. MgD triggers chronic systemic inflammation that also potentiates IR. People with T2D may end up in a vicious circle in which MgD increases IR and IR causes MgD, that requires periodic monitoring of serum Mg2+ levels.
    Keywords magnesium deficiency ; insulin resistance ; type 2 diabetes ; insulin secretion ; insulin signaling ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 571
    Language English
    Publishing date 2019-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article: Changes in Serum Levels of Matrix Metalloproteinase-1 and Tissue Inhibitor of Metalloproteinases-1 in Patients with Essential Hypertension.

    Kostov, Krasimir / Blazhev, Alexander

    Bioengineering (Basel, Switzerland)

    2022  Volume 9, Issue 3

    Abstract: Hypertension (HTN) is a leading risk factor for cardiovascular (CV) disease. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are thought to be actively involved in the remodeling of the CV extracellular matrix (ECM) during ... ...

    Abstract Hypertension (HTN) is a leading risk factor for cardiovascular (CV) disease. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are thought to be actively involved in the remodeling of the CV extracellular matrix (ECM) during hypertensive damage. Therefore, in this study, we aimed to investigate serum levels of MMP-1 and TIMP-1 in patients with essential HTN and compare them with those of normotensive individuals. We measured serum concentrations of MMP-1 and TIMP-1 in 60 patients with HTN and 20 healthy controls using an ELISA. The obtained results showed that in patients with HTN, the mean levels of MMP-1 (1.82 ± 0.9 ng/mL) were significantly higher (
    Language English
    Publishing date 2022-03-15
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2746191-9
    ISSN 2306-5354
    ISSN 2306-5354
    DOI 10.3390/bioengineering9030119
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Elevated IgG and IgM Autoantibodies to Advanced Glycation End Products of Vascular Elastin in Hypertensive Patients with Type 2 Diabetes: Relevance to Disease Initiation and Progression.

    Kostov, Krasimir / Blazhev, Alexander

    Pathophysiology : the official journal of the International Society for Pathophysiology

    2022  Volume 29, Issue 3, Page(s) 426–434

    Abstract: The increased glycation of elastin is an important factor in vascular changes in diabetes. Using the ELISA method, we determined serum levels of IgM and IgG autoantibodies to advanced glycation end products of vascular elastin (anti-AGE EL IgM and anti- ... ...

    Abstract The increased glycation of elastin is an important factor in vascular changes in diabetes. Using the ELISA method, we determined serum levels of IgM and IgG autoantibodies to advanced glycation end products of vascular elastin (anti-AGE EL IgM and anti-AGE EL IgG) in 59 hypertensive patients with type 2 diabetes (T2D) and 20 healthy controls. Serum levels of matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9) and the C-reactive protein (CRP) were also determined. The levels of anti-AGE EL IgM antibodies in the T2D group were similar to those in the control group, while those of anti-AGE EL IgG antibodies were significantly higher (
    Language English
    Publishing date 2022-08-01
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1212740-1
    ISSN 1873-149X ; 0928-4680
    ISSN (online) 1873-149X
    ISSN 0928-4680
    DOI 10.3390/pathophysiology29030034
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  7. Article ; Online: Circulating Levels of Endothelin-1 and Big Endothelin-1 in Patients with Essential Hypertension.

    Kostov, Krasimir / Blazhev, Alexander

    Pathophysiology : the official journal of the International Society for Pathophysiology

    2021  Volume 28, Issue 4, Page(s) 489–495

    Abstract: The role of endothelin-1 (ET-1) in the pathogenesis of hypertension (HTN) is not clearly established. There is evidence that its circulating levels are elevated in some forms of experimental and human HTN, but this was not a consistent finding. Based on ... ...

    Abstract The role of endothelin-1 (ET-1) in the pathogenesis of hypertension (HTN) is not clearly established. There is evidence that its circulating levels are elevated in some forms of experimental and human HTN, but this was not a consistent finding. Based on these controversial data, we tested serum levels of ET-1 and Big ET-1 (the precursor of ET-1) in patients with essential HTN, comparing the results with those of healthy normotensive controls. The levels of ET-1 and Big ET-1 were measured by ELISA. Our results in patients with essential HTN showed that the mean levels of ET-1 (5.01 ± 2.1 pg/mL) were significantly higher (
    Language English
    Publishing date 2021-10-25
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1212740-1
    ISSN 1873-149X ; 0928-4680
    ISSN (online) 1873-149X
    ISSN 0928-4680
    DOI 10.3390/pathophysiology28040031
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Serum Anti-Collagen IV IgM and IgG Antibodies as Indicators of Low Vascular Turnover of Collagen IV in Patients with Long-Term Complications of Type 2 Diabetes.

    Kostov, Krasimir / Blazhev, Alexander

    Diagnostics (Basel, Switzerland)

    2021  Volume 11, Issue 5

    Abstract: Thickening of the vascular basement membrane (BM) is a fundamental structural change in the small blood vessels in diabetes. Collagen type IV (CIV) is a major component of the BMs, and monitoring the turnover of this protein in type 2 diabetes (T2D) can ... ...

    Abstract Thickening of the vascular basement membrane (BM) is a fundamental structural change in the small blood vessels in diabetes. Collagen type IV (CIV) is a major component of the BMs, and monitoring the turnover of this protein in type 2 diabetes (T2D) can provide important information about the mechanisms of vascular damage. The aim of the study was through the use of non-invasive biomarkers of CIV (autoantibodies, derivative peptides, and immune complexes) to investigate vascular turnover of CIV in patients with long-term complications of T2D. We measured serum levels of these biomarkers in 59 T2D patients with micro- and/or macrovascular complications and 20 healthy controls using an ELISA. Matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9) were also tested. In the T2D group, significantly lower levels of CIV markers and significantly higher levels of MMP-2 and MMP-9 were found compared to controls. A significant positive correlation was found between IgM antibody levels against CIV and MMP-2. These findings suggest that vascular metabolism of CIV is decreased in T2D with long-term complications and show that a positive linear relationship exists between MMP-2 levels and CIV turnover in the vascular wall.
    Language English
    Publishing date 2021-05-19
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662336-5
    ISSN 2075-4418
    ISSN 2075-4418
    DOI 10.3390/diagnostics11050900
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  9. Article ; Online: Serum Anti-Collagen IV IgM and IgG Antibodies as Indicators of Low Vascular Turnover of Collagen IV in Patients with Long-Term Complications of Type 2 Diabetes

    Krasimir Kostov / Alexander Blazhev

    Diagnostics, Vol 11, Iss 900, p

    2021  Volume 900

    Abstract: Thickening of the vascular basement membrane (BM) is a fundamental structural change in the small blood vessels in diabetes. Collagen type IV (CIV) is a major component of the BMs, and monitoring the turnover of this protein in type 2 diabetes (T2D) can ... ...

    Abstract Thickening of the vascular basement membrane (BM) is a fundamental structural change in the small blood vessels in diabetes. Collagen type IV (CIV) is a major component of the BMs, and monitoring the turnover of this protein in type 2 diabetes (T2D) can provide important information about the mechanisms of vascular damage. The aim of the study was through the use of non-invasive biomarkers of CIV (autoantibodies, derivative peptides, and immune complexes) to investigate vascular turnover of CIV in patients with long-term complications of T2D. We measured serum levels of these biomarkers in 59 T2D patients with micro- and/or macrovascular complications and 20 healthy controls using an ELISA. Matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9) were also tested. In the T2D group, significantly lower levels of CIV markers and significantly higher levels of MMP-2 and MMP-9 were found compared to controls. A significant positive correlation was found between IgM antibody levels against CIV and MMP-2. These findings suggest that vascular metabolism of CIV is decreased in T2D with long-term complications and show that a positive linear relationship exists between MMP-2 levels and CIV turnover in the vascular wall.
    Keywords type 2 diabetes ; collagen IV ; vascular basement membrane ; matrix metalloproteinases-2 and -9 ; diabetic vascular complications ; Medicine (General) ; R5-920
    Subject code 616
    Language English
    Publishing date 2021-05-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Use of Glycated Hemoglobin (A1c) as a Biomarker for Vascular Risk in Type 2 Diabetes: Its Relationship with Matrix Metalloproteinases-2, -9 and the Metabolism of Collagen IV and Elastin.

    Kostov, Krasimir / Blazhev, Alexander

    Medicina (Kaunas, Lithuania)

    2020  Volume 56, Issue 5

    Abstract: Background and ... ...

    Abstract Background and objectives
    MeSH term(s) Biomarkers/blood ; Case-Control Studies ; Collagen Type IV/blood ; Diabetes Mellitus, Type 2/blood ; Diabetes Mellitus, Type 2/complications ; Diabetic Angiopathies/blood ; Diabetic Angiopathies/diagnosis ; Diabetic Angiopathies/etiology ; Elastin/blood ; Enzyme-Linked Immunosorbent Assay/methods ; Female ; Glycated Hemoglobin A/analysis ; Humans ; Male ; Matrix Metalloproteinase 2/blood ; Matrix Metalloproteinase 9/blood ; Middle Aged ; Risk Assessment
    Chemical Substances Biomarkers ; Collagen Type IV ; Glycated Hemoglobin A ; Elastin (9007-58-3) ; Matrix Metalloproteinase 2 (EC 3.4.24.24) ; Matrix Metalloproteinase 9 (EC 3.4.24.35)
    Language English
    Publishing date 2020-05-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2188113-3
    ISSN 1648-9144 ; 1010-660X
    ISSN (online) 1648-9144
    ISSN 1010-660X
    DOI 10.3390/medicina56050231
    Database MEDical Literature Analysis and Retrieval System OnLINE

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