scholarly journals Polarized Proteins in Endothelium and Their Contribution to Function

2021 ◽  
pp. 1-27
Author(s):  
Abigail G. Wolpe ◽  
Claire A. Ruddiman ◽  
Phillip J. Hall ◽  
Brant E. Isakson
Keyword(s):  
Endothelial Cells ◽  
Endothelial Function ◽  
Planar Cell Polarity ◽  
Protein Localization ◽  
Peripheral Resistance ◽  
Specific Protein ◽  
Resistance Arteries ◽  
Extracellular Stimuli ◽  
Small Resistance ◽  
Signaling Domains

Protein localization in endothelial cells is tightly regulated to create distinct signaling domains within their tight spatial restrictions including luminal membranes, abluminal membranes, and interendothelial junctions, as well as caveolae and calcium signaling domains. Protein localization in endothelial cells is also determined in part by the vascular bed, with differences between arteries and veins and between large and small arteries. Specific protein polarity and localization is essential for endothelial cells in responding to various extracellular stimuli. In this review, we examine protein localization in the endothelium of resistance arteries, with occasional references to other vessels for contrast, and how that polarization contributes to endothelial function and ultimately whole organism physiology. We highlight the protein localization on the luminal surface, discussing important physiological receptors and the glycocalyx. The protein polarization to the abluminal membrane is especially unique in small resistance arteries with the presence of the myoendothelial junction, a signaling microdomain that regulates vasodilation, feedback to smooth muscle cells, and ultimately total peripheral resistance. We also discuss the interendothelial junction, where tight junctions, adherens junctions, and gap junctions all convene and regulate endothelial function. Finally, we address planar cell polarity, or axial polarity, and how this is regulated by mechanosensory signals like blood flow.

scholarly journals SP284BETA-TRACE PROTEIN CORRELATES WITH ENDOTHELIAL FUNCTION IN PERIPHERAL RESISTANCE ARTERIES IN END STAGE RENAL DISEASE

2017 ◽  
Vol 32 (suppl_3) ◽  
pp. iii202-iii202
Author(s):  
Samsul Arefin ◽  
Amaryllis Van Craenenbroeck ◽  
Neja Mudrovcic ◽  
Ann-Christin Bragfors-Helin ◽  
Peter Stenvinkel ◽  
...  
Keyword(s):  
Renal Disease ◽  
Endothelial Function ◽  
End Stage Renal Disease ◽  
Peripheral Resistance ◽  
Resistance Arteries ◽  
Stage Renal Disease ◽  
End Stage

P2250P66Shc mediates the influence of Sirt-1 on age and obesity related endothelial function

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Masi ◽  
E Duranti ◽  
M Chiriaco ◽  
R Mancini ◽  
M Nannipieri ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Promoter Region ◽  
Control Group ◽  
Chip Assay ◽  
Resistance Arteries ◽  
Control Groups ◽  
Age Related ◽  
Small Resistance ◽  
Obese Subjects ◽  
And Control

Abstract Background Sirtuins are histone deacetylase downregulated in conditions of excessive calory intake, with important roles in controlling cellular ageing pathways. Among their different isoforms, Sirt-1 is the most studied and experimental models suggest it could contribute to the downregulation of the ageing protein p66Shc in conditions of reduced energy intake, ultimately resulting in a reduced mitochondrial free radical production (mtROS). Purpose We assessed the combined influence of ageing and obesity (a condition of excessive calory intake) on the expression and functional activity of Sirt-1 in humans small resistance arteries, as well as whether the effects of Sirt-1 on endothelial function might depend from the regulation of p66Shc activity and its influence on mtROS. Methods Small resistance arteries were isolated from subcutaneous tissue of obese subjects and healthy controls undergoing bariatric surgery of inguinal hernia repair, respectively. The obese and control groups were further divided into young (<40 years old) and old (>40 years old) subjects. Arteries were mounted on a pressurised myograph and endothelial function was assessed using dose-response curves to acetylcholine before and after incubation with SRT1720 (selective agonist of Sirt-1), L-NAME (eNOS inhibitor), MitoTEMPO (mtROS scavenger) and gp91ds-tat (NADPH oxidase inhibitor), alone or in combination. The expression of Sirt-1 and p66Shc in the vascular wall of obese and control subjects was assessed by qPCR while the ChIP assay was used to assess the binding of Sirt-1 to the promoter region of p66Shc. Results Endothelial function was lower in older than younger and in obese than control groups (p<0.001). Incubation with SRT1720 did not affect endothelial function in young controls, slightly improved endothelial function in young obese (p<0.01) and induced a substantial improvement in endothelial function in both the old control and old obese groups (p<0.001). Pre-incubation with L-NAME suggested that the effects of Sirt-1 were dependent from an improved vascular NO availability. Incubation with gp91ds-tat improved endothelial function in both obese groups and the old control group (p<0.01), but to a lesser extent than SRT1720. Conversely, incubation with MitoTEMPO induced the same improvement of endothelial function than SRT1720 in all study groups and, when vessels were preincubated with MitoTEMPO, the addition of Sirt-1 did not produce further improvement of endothelial function. The expression of Sirt-1 and p66Shc was increased in the vessels from obese subjects compared to the non-obese group (p<0.001), while the ChIP assay revealed a lower binding of Sirt-1 to the promoter region of p66Shc in obese than controls subjects (p<0.001). Conclusions Our results suggest that Sirt-1 has an important role in the obesity and age-related endothelial dysfunction, throughout epigenetic regulation of p66Shc and, thus, controlling the production of mtROS. Acknowledgement/Funding Ministero dell'istruzione, dell'università e della ricerca

Microcirculation and Macrocirculation in Hypertension: A Dangerous Cross-Link?

Hypertension ◽  
2022 ◽  
Author(s):  
Stephane Laurent ◽  
Claudia Agabiti-Rosei ◽  
Rosa Maria Bruno ◽  
Damiano Rizzoni
Keyword(s):  
Total Peripheral Resistance ◽  
Peripheral Resistance ◽  
Left Ventricular ◽  
Vicious Circle ◽  
Large Artery ◽  
Resistance Arteries ◽  
Cross Link ◽  
Small Artery ◽  
Structural Abnormalities ◽  
Small Resistance

Microcirculation and macrocirculation are tightly interconnected into a dangerous cross-link in hypertension. Small artery damage includes functional (vasoconstriction, impaired vasodilatation) and structural abnormalities (mostly inward eutrophic remodeling). These abnormalities are major determinants of the increase in total peripheral resistance and mean blood pressure (BP) in primary hypertension, which in the long term induces large artery stiffening. In turn, large artery stiffening increases central systolic and pulse pressures, which are further augmented by wave reflection in response to the structural alterations in small resistance arteries. Finally, transmission of high BP and flow pulsatility to small resistance arteries further induces functional and structural abnormalities, thus leading to increased total peripheral resistance and mean BP, thus perpetuating the vicious circle. Hyperpulsatility, in addition to higher mean BP, exaggerates cardiac, brain, and kidney damages and leads to cardiovascular, cerebral, and renal complications. The dangerous cross-link between micro and macrocirculation can be reversed into a virtuous one by ACE (angiotensin-converting enzyme) inhibitors, sartans, and calcium channel blockers. These three pharmacological classes are more potent than β-blockers and diuretics for reducing arterial stiffness and small artery remodeling. The same ranking was observed for their effectiveness at reducing left ventricular hypertrophy, preserving glomerular filtration rate, and preventing dementia, suggesting that they can act beyond brachial BP reduction, by breaking the micro/macrocirculation vicious circle.

Cytokines and vascular reactivity in resistance arteries

2005 ◽  
Vol 288 (3) ◽  
pp. H1016-H1021 ◽  
Author(s):  
Elisabet Vila ◽  
Mercedes Salaices
Keyword(s):  
Vascular Reactivity ◽  
Peripheral Resistance ◽  
Resistance Arteries ◽  
Vascular Effects ◽  
Arterial Blood ◽  
Vasoactive Mediators ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Small Resistance ◽  
Vascular Beds

Cytokine levels are elevated in many cardiovascular diseases and seem to be implicated in the associated disturbances in vascular reactivity reported in these diseases. Arterial blood pressure is maintained within a normal range by changes in peripheral resistance and cardiac output. Peripheral resistance is mainly determined by small resistance arteries and arterioles. This review focuses on the effects of cytokines, mainly TNF-α, IL-1β, and IL-6, on the reactivity of resistance arteries. The vascular effects of cytokines depend on the balance between the vasoactive mediators released under their influence in the different vascular beds. Cytokines may induce a vasodilatation and hyporesponsiveness to vasoconstrictors that may be relevant to the pathogenesis of septic shock. Cytokines may also induce vasoconstriction or increase the response to vasoconstrictor agents and impair endothelium-dependent vasodilatation. These effects may help predispose to vessel spasm, thrombosis, and atherogenesis and reinforce the link between inflammation and vascular disease.

scholarly journals NADPH oxidase 4 has a crucial impact on the microcirculation of hypercholesteremic LDL receptor deficient mice

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
P Diaba-Nuhoho ◽  
A Shahid ◽  
C Brunssen ◽  
H Morawietz ◽  
H Brendel
Keyword(s):  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
Mouse Model ◽  
Nadph Oxidase ◽  
Endothelial Function ◽  
Vascular Function ◽  
Mesenteric Arteries ◽  
Resistance Arteries ◽  
Enos Expression ◽  
Small Resistance

Abstract Introduction NADPH oxidase (NOX) 4-generated H2O2 has anti-atherosclerotic properties in conduit arteries like the aorta and carotids. However, the role of NOX4 on vascular function of small resistance arteries and blood pressure in a mouse model of familial hypercholesterolemia is unknown. Purpose We evaluated whether NOX4-generated H2O2 might play a role in perivascular adipose tissue of the thoracic aorta (tPVAT) and small resistance arteries on vascular function in a mouse model of familial hypercholesterolemia. Methods Aortic segments and mesenteric arteries from 26-week-old Ldlr−/− and Nox4−/− / Ldlr−/− mice were analysed by Mulvany myograph. In addition, vascular contraction and relaxation was analysed in the presence of L-NAME and catalase. Analysis of mRNA expression was performed in murine and human tissue by quantitative real-time PCR. Blood pressure was detected by tail cuff method in conscious, trained mice. Results Loss of NOX4 led to severe endothelial dysfunction in mesenteric arteries of Ldlr−/− mice. Blocking of NO synthases with L-NAME led to decreased endothelial relaxation in Ldlr−/− mice at the level of Nox4−/− / Ldlr−/− mice. However, incubation with L-NAME did not worsen the established endothelial dysfunction of the mesenteric arteries from Nox4−/− / Ldlr−/− mice. These results are strikingly different from the aorta, where inhibition of NO synthases led to a similarly impaired endothelial relaxation in both mouse strains. We detected a similar eNOS expression in the aorta of Ldlr−/− and Nox4−/− / Ldlr−/−, but a reduced eNOS expression in the mesenteric arteries of Nox4−/− / Ldlr−/− mice. H2O2 can induce eNOS expression. Therefore, we analysed the vascular function after catalase incubation and again found a significant reduction of endothelial function in the mesenteric arteries of Ldlr−/− mice. Finally, we analysed blood pressure of these mice and did not observe differences in systolic blood pressure, despite significant differences in endothelial function of resistant arteries. Conclusion NOX4 protects against severe endothelial dysfunction in the mesenteric artery in a model of hypercholesterolemia. FUNDunding Acknowledgement Type of funding sources: Other. Main funding source(s): Ghanaian-German postgraduate training scholarship program (DAAD)

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