Activated Platelets from Diabetic Rats Cause Endothelial Dysfunction by Decreasing Akt/Endothelial NO Synthase Signaling Pathway

Recent data suggest that diabetes is a risk factor for pulmonary hypertension. The aim of the present study was to analyze whether diabetes induces endothelial dysfunction in pulmonary arteries and the mechanisms involved. Male Sprague-Dawley rats were randomly divided into a control (saline) and a diabetic group (70 mg/kg−1 streptozotocin). After 6 wk, intrapulmonary arteries were mounted for isometric tension recording, and endothelial function was tested by the relaxant response to acetylcholine. Protein expression and localization were measured by Western blot and immunohistochemistry and superoxide production by dihydroethidium staining. Pulmonary arteries from diabetic rats showed impaired relaxant response to acetylcholine and reduced vasoconstrictor response to the nitric oxide (NO) synthase inhibitor l-NAME, whereas the response to nitroprusside and the expression of endothelial NO synthase remained unchanged. Endothelial dysfunction was reversed by addition of superoxide dismutase or the NADPH oxidase inhibitor apocynin. An increase in superoxide production and increased expression of the NADPH oxidase regulatory subunit p47phox were also found in pulmonary arteries from diabetic rats. In conclusion, the pulmonary circulation is a target for diabetes-induced endothelial dysfunction via enhanced NADPH oxidase-derived superoxide production.

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The gene polymorphism of endothelial NO-synthase and the structural and functional state of large vessels in hypertensive patients with left ventricular hypertrophy

Arterial’naya Gipertenziya (Arterial Hypertension) ◽

10.18705/1607-419x-2005-11-3-195-200 ◽

2005 ◽

Vol 11 (3) ◽

pp. 195-200 ◽

Cited By ~ 1

Author(s):

O. I. Yakovleva ◽

N. V. Vakhrameyeva ◽

V. I. Larionova ◽

M. A. Bogdanova ◽

A. O. Konradi

Keyword(s):

Endothelial Dysfunction ◽

Left Ventricular Hypertrophy ◽

Gene Polymorphism ◽

Ventricular Hypertrophy ◽

Left Ventricular ◽

No Synthase ◽

Hypertensive Disease ◽

Large Arteries ◽

Endothelial No Synthase ◽

The Impact

Remodeling of large arteries and endothelial dysfunction, as left ventricular hypertrophy, is associated with the development of severe cardiovascular events and worse prognosis in patients with hypertensive disease. The impact of genetic determinants on the development of such lesions to target organs in this group of patients was the subject of wide speculation. We determined the genotype of endothelial NO-synthase (the polymorphisms 4a/4b and Glu298Asp) in 51 patients (28 males and 23 females; mean age |48,0±6,3 years) with hypertensive disease and left ventricular hypertrophy; the profile of blood pressure (BP) was assessed by its 24-hour monitoring data; the thickness of an intima-media complex was measured during ultrasound study. Endothelial function was determined by the increase in the diameter of the brachial artery during a reactive hyperemia test. The remodeling of large arteries in the examinees was found to be associated with both the average BP levels and age. There was no relationship of the gene polymorphism of endothelial NO-synthase to the daily BP profile and the remodeling of the large arteries alike. Endothelial dysfunction in t lie examinees was associated with the carriage of the mutant allele T of the gene of endothelial NO-synthase.

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Chronic periodontitis and ischemic heart disease: morphofunctional relation-ships

Российский стоматологический журнал ◽

10.17816/1728-2802-2020-24-4-219-224 ◽

2020 ◽

Vol 24 (4) ◽

pp. 219-224

Author(s):

Andrey V. Eremin ◽

A. V. Lepilin ◽

T. E. Lipatova ◽

I. M. Kvetnoy

Keyword(s):

Heart Disease ◽

Endothelial Dysfunction ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Chronic Periodontitis ◽

Vascular Wall ◽

No Synthase ◽

Endothelial Progenitor ◽

Endothelial No Synthase ◽

Cd34 Cells

The relationship between periodontal diseases and cardiovascular pathology is actively being studied. The clinical significance of tissue markers of endothelial dysfunction in acute or chronic periodontitis needs to be clarified. Materials and methods. The results of the examination of 65 patients with chronic generalized periodontitis (CP), 35 patients with chronic coronary heart disease (CHD), and 35 patients with combined pathology including CHD and CP were presented. Clinical instrumental examination, assessment of the functional state of the endothelium, immunohistochemical, and morphometric studies were performed. Results. Patients with moderate CP were characterized by functional changes in the endothelium, decreased expression of the vasodilating factor (e-NO-synthase), and endothelial progenitor cells (CD34+cells) in the vascular wall. In patients with CHD without periodontitis, there was also a decrease in the expression and optical density of endothelial NO-synthase and endothelial progenitor cell in the periodontal vessels. Conclusion. Apparently, changes in the expression of endothelial NO-synthase and endothelial progenitor cells (CD34+cells) in the vascular wall are generalized, and the gum can serve as a promising material for the early assessment of endothelial dysfunction.

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Vitamin D Is a Regulator of Endothelial Nitric Oxide Synthase and Arterial Stiffness in Mice

Molecular Endocrinology ◽

10.1210/me.2013-1252 ◽

2014 ◽

Vol 28 (1) ◽

pp. 53-64 ◽

Cited By ~ 106

Author(s):

Olena Andrukhova ◽

Svetlana Slavic ◽

Ute Zeitz ◽

Sabine C. Riesen ◽

Monika S. Heppelmann ◽

...

Keyword(s):

Nitric Oxide ◽

Vitamin D ◽

Endothelial Dysfunction ◽

Arterial Stiffness ◽

Epidemiological Data ◽

Vitamin D Insufficiency ◽

Left Ventricular ◽

No Synthase ◽

Mutant Mice ◽

Endothelial No Synthase

Abstract The vitamin D hormone 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] is essential for the preservation of serum calcium and phosphate levels but may also be important for the regulation of cardiovascular function. Epidemiological data in humans have shown that vitamin D insufficiency is associated with hypertension, left ventricular hypertrophy, increased arterial stiffness, and endothelial dysfunction in normal subjects and in patients with chronic kidney disease and type 2 diabetes. However, the pathophysiological mechanisms underlying these associations remain largely unexplained. In this study, we aimed to decipher the mechanisms by which 1,25(OH)2D3 may regulate systemic vascular tone and cardiac function, using mice carrying a mutant, functionally inactive vitamin D receptor (VDR). To normalize calcium homeostasis in VDR mutant mice, we fed the mice lifelong with the so-called rescue diet enriched with calcium, phosphate, and lactose. Here, we report that VDR mutant mice are characterized by lower bioavailability of the vasodilator nitric oxide (NO) due to reduced expression of the key NO synthesizing enzyme, endothelial NO synthase, leading to endothelial dysfunction, increased arterial stiffness, increased aortic impedance, structural remodeling of the aorta, and impaired systolic and diastolic heart function at later ages, independent of changes in the renin-angiotensin system. We further demonstrate that 1,25(OH)2D3 is a direct transcriptional regulator of endothelial NO synthase. Our data demonstrate the importance of intact VDR signaling in the preservation of vascular function and may provide a mechanistic explanation for epidemiological data in humans showing that vitamin D insufficiency is associated with hypertension and endothelial dysfunction.

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Metabolic Syndrome: the Influence of Adipokines on the L-Arginine-NO Synthase-Nitric Oxide Signaling Pathway

Acta biomedica scientifica ◽

10.29413/abs.2021-6.2.3 ◽

2021 ◽

Vol 6 (2) ◽

pp. 22-40

Author(s):

L. A. Kuznetsova

Keyword(s):

Metabolic Syndrome ◽

Protein Kinase ◽

Signaling Pathway ◽

Posttranslational Modifications ◽

Maximum Activity ◽

No Synthase ◽

Akt Kinase ◽

Nitric Oxide Signaling ◽

Endothelial No Synthase ◽

No Signaling

Metabolic syndrome includes the following symptoms: obesity, hyperlipidemia, hypertension, insulin resistance, and cardiovascular disease. The purpose of this review is to elucidate the role of adipokines in the regulation of the L-arginine-NO-synthas-NO signaling pathway in the pathogenesis of metabolic syndrome. The main questions raised in the review are: how adipokine secretion changes, how the level of their receptors is regulated, and which signaling pathways are involved in the transmission of adipokine signals when coupled to the L-arginine-NO-synthase-NO signaling cascade. Adipokines are peptide hormones that transmit a signal from adipose tissue to targets in the brain, blood vessels, liver, pancreas, muscles, and other tissues. Some adipokines have anti-inflammatory and insulin-sensitive effects: adiponectin, omentin, adipolin, chemerin, progranulin. Others have the negative inflammatory effect in the development ofmetabolic syndrome: visfatin, vaspin, apelin. Adipokines primarily regulate the expression and activity of endothelial NO-synthase. They either activate an enzyme involving 5-AMP protein kinase or Akt kinase, increasing its activity and synthesis of NO in the tissues of healthy patients: adiponectin, adipolin, omentin, or inhibit the activity of eNOS, which leads to a decrease in NO-synthase and suppression of mRNA bioavailability: vaspin, visfatin, apelin in metabolic syndrome, and a decrease in its activity leads to dissociation and endothelial dysfunction. It should be noted that the bioavailability of NO formed by NO-synthase is affected at many levels, including: the expression ofNO-synthase mRNA and its protein; the concentration of L-arginine; the level of cofactors of the reaction; and to detect the maximum activity of endothelial NO-synthase, dimerization of the enzyme is required, posttranslational modifications are important, in particular, phosphorylation of endothelial NO-synthase by serine 1177 with the participation of 5-AMP protein kinase, Akt kinase and other kinases. It should be noted that the participation of adiponectin, omentin, and kemerin in the regulation of the L-arginine-NO-synthase-NO cascade in metabolic syndrom opens up certain opportunities for the development of new approaches for the correction of disorders observed in this disease. The review analyzes the results of research searching in PubMed databases, starting from 2001 and up to 2020 using keywords and adipokine names, more than half of the references of the last 5 years.

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26. Chronic periodontitis and endothelial dysfunction In patients with arterial hypertension

Archiv Euromedica ◽

10.35630/2199-885x/2021/11/4.26 ◽

2021 ◽

Vol 11 (4) ◽

pp. 108-110

Author(s):

Andrey Eremin ◽

Alexandr Lepilin ◽

Tatiana Lipatova

Keyword(s):

Endothelial Dysfunction ◽

Inflammatory Response ◽

Arterial Hypertension ◽

Clinical Examination ◽

Chronic Periodontitis ◽

No Synthase ◽

Systemic Inflammatory Response ◽

Endothelial No Synthase ◽

Vasoactive Mediators

The work offers a view at the data obtained through an examination of 120 patients with chronic generalized periodontitis (CP) and arterial hypertension (AH). The check-up included clinical examination, immunohistochemical, morphometric studies, as well as evaluation of the endothelium vasodilating function. CP in patients with hypertension features more significant changes in the quantitative density of gum cells positive to ET-1, endothelial NO-synthase, if compared to the CP values in patients with no background somatic pathology. Changes affecting vasoactive mediators in the gum are associated with a systemic inflammatory response and a violation of the endothelium vasodilating function. Periodontitis remission can be achieved with the therapy of the neurotransmitter imbalance.

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