Modulation of Nitric Oxide Synthases by Oxidized LDLs: Role in Vascular Inflammation and Atherosclerosis Development

Gliozzi, Micaela; Scicchitano, Miriam; Bosco, Francesca; Musolino, Vincenzo; Carresi, Cristina; Scarano, Federica; Maiuolo, Jessica; Nucera, Saverio; Maretta, Alessia; Paone, Sara; Mollace, Rocco; Ruga, Stefano; Zito, Maria Caterina; Macrì, Roberta; Oppedisano, Francesca; Palma, Ernesto; Salvemini, Daniela; Muscoli, Carolina; Mollace, Vincenzo

doi:10.3390/ijms20133294

Cited by 169 publications

(113 citation statements)

References 99 publications

(126 reference statements)

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“…The activated TLR4 on macrophages can trigger a cascade of signaling events, inducing inflammatory cytokines, and proteases. OxLDL, a TLR4 agonist, is responsible for early endothelial dysfunction and its link to TLR4 contributes to the initiation of atherosclerosis [ [76] , [77] , [78] , [79] ]. The activation of this receptor may also promote the instability of atherosclerotic plaques and enhance their susceptibility for physical disruption and acute thrombosis [ 80 ].…”

Section: Toll-like Receptorsmentioning

confidence: 99%

Is Toll-like receptor 4 involved in the severity of COVID-19 pathology in patients with cardiometabolic comorbidities?

Brandão

Ramos

Dompieri

et al. 2021

Cytokine & Growth Factor Reviews

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Highlights Some inflammatory diseases are related to severe forms of COVID-19, characterized by an immune system overactivation. SARS-CoV-2 Spike protein binds with human innate immune receptors, mainly TLR4, increasing secretion of IL‐ 6 and TNF‐ α. The main inflammatory diseases seen as risk factors for COVID-19 are hypertension, diabetes, obesity, and atherosclerosis. The TLR4 signaling pathway is connected to inflammatory diseases seen as risk factors for COVID-19.

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Section: Toll-like Receptorsmentioning

confidence: 99%

Is Toll-like receptor 4 involved in the severity of COVID-19 pathology in patients with cardiometabolic comorbidities?

Brandão

Ramos

Dompieri

et al. 2021

Cytokine & Growth Factor Reviews

View full text Add to dashboard Cite

show abstract

“…iNOS derived NO is closely correlated with inflammation and apoptosis in the cardiovascular system. 21 To investigate whether ER stress promotes apoptosis through the iNOS/NO-NF-κB signaling pathway and the NLRP3 inflammasome, we analyzed apoptosis in HUVECs. Compared with controls, increased levels of apoptosis were found in MG, which were attenuated by inhibiting ER stress with TUDCA/4-PBA ( Figure 2C,D).…”

Section: Huvecs Through the Inos/no-mediated Nf-κb Signaling Pathway mentioning

confidence: 99%

Endoplasmic reticulum stress‐dependent activation of iNOS/NO‐NF‐κB signaling and NLRP3 inflammasome contributes to endothelial inflammation and apoptosis associated with microgravity

et al. 2020

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Exposure to microgravity results in vascular remodeling and cardiovascular dysfunction. To elucidate the mechanism involved in this condition, we investigated whether endoplasmic reticulum (ER) stress during simulated microgravity induced endothelial inflammation and apoptosis in human umbilical vein endothelial cells (HUVECs). Microgravity was simulated by clinorotation in the current study. We examined markers of ER stress, inducible nitric oxide (NO) synthase (iNOS)/NO content, proinflammatory cytokine production, nuclear factor kappa B (NF-κB)/IκB signaling, NLRP3 inflammasome, and detected apoptosis in HUVECs. We found that the levels of C/EBP homologous protein and glucose-regulated protein 78, proinflammatory cytokines (IL-6, TNF-α, IL-8, and IL-1β), and iNOS/NO content were upregulated by clinorotation. ER stress inhibition with tauroursodeoxycholic acid or 4-phenylbutyric acid and iNOS inhibition with 1400 W dramatically suppressed activation of the NF-κB/IκB pathway and the NLRP3 inflammasome, and decreased the production of pro-inflammatory cytokines. The increase of apoptosis in HUVECs during clinorotation was significantly suppressed by inhibiting ER stress, iNOS activity, NF-κB/IκB, and the NLRP3 inflammasome signaling pathway. Therefore, simulated microgravity causes ER stress in HUVECs, and subsequently activates iNOS/NO-NF-κB/IκB and the NLRP3 inflammasome signaling pathway, which have key roles in the induction of endothelial inflammation and apoptosis.

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“…Hypercholesterolemia is considered one of the main risk factors for the development of atherosclerosis [2,6,119,127,128]. The atherogenic endothelial phenotype has higher permeability to circulating LDL.…”

Section: Hypercholesterolemiamentioning

confidence: 99%

Use of Human Umbilical Vein Endothelial Cells (HUVEC) as a Model to Study Cardiovascular Disease: A Review

et al. 2020

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Cardiovascular disease (CVD) is the leading cause of death worldwide, and extensive research has been performed to understand this disease better, using various experimental models. The endothelium plays a crucial role in the development of CVD, since it is an interface between bloodstream components, such as monocytes and platelets, and other arterial wall components. Human umbilical vein endothelial cell (HUVEC) isolation from umbilical cord was first described in 1973. To date, this model is still widely used because of the high HUVEC isolation success rate, and because HUVEC are an excellent model to study a broad array of diseases, including cardiovascular and metabolic diseases. We here review the history of HUVEC isolation, the HUVEC model over time, HUVEC culture characteristics and conditions, advantages and disadvantages of this model and finally, its applications in the area of cardiovascular diseases.

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Modulation of Nitric Oxide Synthases by Oxidized LDLs: Role in Vascular Inflammation and Atherosclerosis Development

Cited by 169 publications

References 99 publications

Is Toll-like receptor 4 involved in the severity of COVID-19 pathology in patients with cardiometabolic comorbidities?

Is Toll-like receptor 4 involved in the severity of COVID-19 pathology in patients with cardiometabolic comorbidities?

Endoplasmic reticulum stress‐dependent activation of iNOS/NO‐NF‐κB signaling and NLRP3 inflammasome contributes to endothelial inflammation and apoptosis associated with microgravity

Use of Human Umbilical Vein Endothelial Cells (HUVEC) as a Model to Study Cardiovascular Disease: A Review

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