Endothelial Nitric Oxide Synthase (eNOS) and the Cardiovascular System: in Physiology and in Disease States

Nauli, Surya M.

doi:10.34297/ajbsr.2022.15.002087

Cited by 25 publications

(9 citation statements)

References 209 publications

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“…5C, 5D and 5F), it stimulates endothelial cells, probably through endothelial nitric oxide synthases (eNOS or NOS3) to produce nitric oxide (NO). It was con med by in vivo studies, in which the dose of 100 mg/kg (91.86 ± 12.31µM) markedly increased indirect levels of nitric oxide quanti ed as nitrite content, which could be one of the factors responsible for inhibiting platelet aggregation (Radomski et al 1990;Tran et al 2022). This method was established using a calibration curve (R 2 = 0.9942) (Fig.…”

Section: Antiplatelet Effect and Nitrite Dosage Of γ-Tpnmentioning

confidence: 99%

Non-clinical investigations about cytotoxic and anti-platelet activities of gamma-terpinene

Souza,

Pimentel,

de Sousa

et al. 2024

Naunyn-Schmiedeberg's Arch Pharmacol

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Gamma-terpinene (γ-TPN) is a cyclohexane monoterpene, isolated from essential oils of pharmacologically active plant species, such as tea tree (Melaleuca alternifolia), oregano (Origanum vulgare), rosemary (Rosmarinus o cinalis L.), thyme (Thymus vulgaris Marchand) and eucalyptus (Eucalyptus sp.). Terpenes are widely studied for their recognized pharmacological actions on the cardiovascular system, hemostasis and antioxidant actions. The objective of this study was to investigate the cytotoxic and antiplatelet activity of γ-TPN in non-clinical study models. For the in silico evaluation, the PreADMET, SwissADME and SwissTargetPrediction software were used. Molecular docking was performed using the AutoDockVina and BIOVIA Discovery Studio databases. The cytotoxicity of γ-TPN was analyzed by the MTT assay with normal murine endothelial (SVEC4-10) and broblast (L929) lines. Platelet aggregation was evaluated with platelet-rich (PRP) and platelet-poor (PPP) plasma from spontaneously hypertensive rats (SHR), in addition to SVEC4-10 cells pre-incubated with γ-TPN (50, 100 and 200 µM) for 24 h. In in vivo tests, SHR animals were also used, pre-treated by gavage with γ-TPN for 7 days, distributed into four groups (control, 25, 50 and 100 mg/Kg). At the end, blood samples were collected to measure nitrites using the Griess reagent. γ-TPN proved to be quite lipid-soluble (Log P = + 4.50), with a quali ed pro le of similarity to the drug, good bioavailability, and adequate pharmacokinetics. The monoterpene exhibited a nity mainly for the P2Y12 receptor (6.450 ± 0.232 Kcal/mol), moderate cytotoxicity for L929 (CC 50 = 333.3 µM) and SVEC 4-10 (CC 50 = 366.7 µM). The presence of γ-TPN in SVEC 4-10 cells was also able to reduce platelet aggregation by 51.57 and 44.20%, respectively, at the lowest concentrations (50 and 100 µM). It was concluded that γ-TPN has a good a nity with purinergic receptors and an effect on the reversal of platelet aggregation and oxidative stress, being promising and safe for therapeutic targets and subsequent studies in the control of thromboembolic diseases.

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Section: Antiplatelet Effect and Nitrite Dosage Of γ-Tpnmentioning

confidence: 99%

Non-clinical investigations about cytotoxic and anti-platelet activities of gamma-terpinene

Souza,

Pimentel,

de Sousa

et al. 2024

Naunyn-Schmiedeberg's Arch Pharmacol

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“…The circular layers exhibit a tendency for impeding hemodynamic circulation, whereas the longitudinal sections, if present, exert a retractile force on the vasculature, causing it to recede into the adjacent tissue. In relation to vessel injury, it is postulated that the release of endothelin (ET -1,2,3) by endothelial cells and nociceptors triggers the vascular spasm response [2]. This particular phenomenon generally exhibits a duration of approximately 30 minutes, although it may persist for extended periods of time depending on the gravity of the injury and the promptness of the body's essential physiological mechanisms in mounting a response.…”

Section: Introductionmentioning

confidence: 99%

Elevated factor VIII level: An implication for thrombosis during pregnancy

Chikamso Favour Agbo,

Freedom Amarachi Nkwocha,

Reuben Chukwuma Odo

et al. 2023

Open Access Res. J. Life Sci.

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Hemostasis is the process by which the body maintains the integrity of blood vessels and regulates blood circulation. It involves arresting bleeding, and possibly mending broken or severed blood vessels. It is achieved through a series of steps, including vascular spasm, platelet plug formation, coagulation cascade, and fibrinolysis. Skipping any of these steps causes severe bleeding and death. During pregnancy, the hemostatic system undergoes significant changes to adapt to the physiological demands. These changes aim to prevent excessive bleeding during and after childbirth. Hypercoagulability, characterized by elevated clotting factors and reduced fibrinolytic activity, is common during pregnancy. While these alterations in the coagulation system help prevent postpartum bleeding, they also increase the mother's risk of thrombosis by a factor of five. This hypercoagulable state is caused by pregnancy-related factors like venous stasis, endothelial damage, and hormonal fluctuations. However, studies have shown that an increase in Factor VIII levels poses as a risk factor for both venous and arterial thrombosis. The determination of plasma factor VIII levels is influenced by genetic factors, as well as the levels of von Willebrand factor (VWF) and the individual's blood group. The findings of familial investigations have revealed that the concentration of factor VIII is indeed hereditary, exhibiting a lesser degree of variability among twins when compared with individuals who lack a familial connection. Continuous monitoring should be performed on pregnant patients with thrombosis risk factors. This intervention is implemented with the aim of mitigating the potential aggravation of deep vein thrombosis (DVT) and the subsequent development of post-thrombotic syndrome.

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“…Hence, it remains urgent to search for new therapies capable to efficiently re-establish perfusion and provide oxygen and nutrients to mitigate ischemic damages. During MI, ischemia and healing cardiac tissue trigger a cascade of signaling reactions involving an increase in reactive oxygen species (ROS) and intracellular Ca 2+ levels, a dysregulation of endothelial NO synthase (eNOS) [5][6][7], and the activation of hypoxia-induced factor dysregulation of endothelial NO synthase (eNOS) [5][6][7], and the activation of hypoxiainduced factor 1α (HIF-1α) required for blood vessels formation from pre-existing vasculature, an action carried out by endothelial cells (ECs) known as angiogenesis [8], as summarized in Figure 1. In addition to the role of ECs in post-infraction angiogenesis, many reports demonstrated that most cell populations of the heart, including cardiomyocytes, macrophages, fibroblasts, and monocytes, participate in this process because they express a high amount of vascular endothelial growth factor (VEGF), the proangiogenic factor par excellence, up to one week after the ischemic event, and other growth factors.…”

Section: Introductionmentioning

confidence: 99%

New Insights into the Reparative Angiogenesis after Myocardial Infarction

Martín-Bórnez,

Falcón,

Morrugares

et al. 2023

IJMS

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Myocardial infarction (MI) causes massive loss of cardiac myocytes and injury to the coronary microcirculation, overwhelming the limited capacity of cardiac regeneration. Cardiac repair after MI is finely organized by complex series of procedures involving a robust angiogenic response that begins in the peri-infarcted border area of the infarcted heart, concluding with fibroblast proliferation and scar formation. Efficient neovascularization after MI limits hypertrophied myocytes and scar extent by the reduction in collagen deposition and sustains the improvement in cardiac function. Compelling evidence from animal models and classical in vitro angiogenic approaches demonstrate that a plethora of well-orchestrated signaling pathways involving Notch, Wnt, PI3K, and the modulation of intracellular Ca2+ concentration through ion channels, regulate angiogenesis from existing endothelial cells (ECs) and endothelial progenitor cells (EPCs) in the infarcted heart. Moreover, cardiac repair after MI involves cell-to-cell communication by paracrine/autocrine signals, mainly through the delivery of extracellular vesicles hosting pro-angiogenic proteins and non-coding RNAs, as microRNAs (miRNAs). This review highlights some general insights into signaling pathways activated under MI, focusing on the role of Ca2+ influx, Notch activated pathway, and miRNAs in EC activation and angiogenesis after MI.

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Endothelial Nitric Oxide Synthase (eNOS) and the Cardiovascular System: in Physiology and in Disease States

Cited by 25 publications

References 209 publications

Non-clinical investigations about cytotoxic and anti-platelet activities of gamma-terpinene

Non-clinical investigations about cytotoxic and anti-platelet activities of gamma-terpinene

Elevated factor VIII level: An implication for thrombosis during pregnancy

New Insights into the Reparative Angiogenesis after Myocardial Infarction

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