Similar inflammatory response and conduit artery vascular function between sexes following induced inflammation

Background: Bone marrow-derived progenitor cells (PCs) are involved in vascular regeneration and correlate with vascular function and cumulative cardiovascular risk. Systemic inflammation is associated with increased mobilization and differentiation of circulating PCs (CPCs) which may ultimately lead to exhaustion of vascular regenerative capacity. Individuals with coronary artery disease (CAD) exhibit a pro-inflammatory response to a mental stress challenge that has been associated with an elevated risk of adverse outcomes. We sought to determine whether subjects with reduced numbers of circulating PCs (CPCs) are at higher risk of a pro-inflammatory response to acute mental stress. Methods: 500 outpatients with stable CAD were enrolled into the Mental Stress Ischemia Prognosis study and underwent a laboratory-based mental stress protocol. Mononuclear cells expressing CD45med, CD34 and CXCR4 epitopes, known to be enriched for hematopoietic PCs, were enumerated using flow cytometry. Interleukin-6 (IL6) and C-Reactive Protein (CRP) levels were measured before and after mental stress. Baseline and changes in IL6 levels were compared across CPC tertiles using linear regression after adjusting for patient characteristics. Results: Mean age was 63± 9 years, 77% male, 70% white. Median CD34+ CPC count was 1.64 (1.02-2.43 cells/μL. CPC levels were not associated with either the baseline IL6 level (Beta= 0.071 95%CI, -0.091, 0.23) or CRP levels (Beta, 0.60, 95%CI, -0.25, 0.44). However, independent of demographics, CAD risk factors and baseline IL6 levels, lower CD34+/CXCR4+ CPC counts were associated with a higher inflammatory response during mental stress, measured as a rise in IL6 level (Beta= -0.11, 95%CI, -0.20, -0.028). Conclusions: Patients with reduced CPC levels have a greater pro-inflammatory response to mental stress. Thus, the observed higher risk in subjects with impaired regenerative capacity might be at least partly due to a higher stress-related pro-inflammatory response.

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Heterogeneity in conduit artery function in humans: impact of arterial size

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00405.2008 ◽

2008 ◽

Vol 295 (5) ◽

pp. H1927-H1934 ◽

Cited By ~ 95

Author(s):

Dick H. J. Thijssen ◽

Ellen A. Dawson ◽

Mark A. Black ◽

Maria T. E. Hopman ◽

N. Timothy Cable ◽

...

Keyword(s):

Shear Rate ◽

Vascular Function ◽

Time Course ◽

Inverse Correlation ◽

Common Femoral Artery ◽

Ultrasound Images ◽

Flow Mediated Dilation ◽

Functional Responses ◽

Conduit Artery ◽

Influence Functional

To determine whether conduit artery size affects functional responses, we compared the magnitude, time course, and eliciting shear rate stimulus for flow-mediated dilation (FMD) in healthy men ( n = 20; 31 ± 7 yr). Upper limb (brachial and radial) and lower limb (common and superficial femoral) FMD responses were simultaneously assessed, whereas popliteal responses were measured in the same subjects during a separate visit. Glyceryl trinitrate (GTN)-mediated responses were similarly examined. Edge detection and wall tracking of high-resolution B-mode arterial ultrasound images, combined with synchronized Doppler waveform envelope analysis, were used to calculate conduit artery diameter, blood flow, and shear rate continuously across the cardiac cycle. Baseline artery size correlated inversely with the FMD response ( r = −0.57, P < 0.001). Within-artery comparisons revealed a significant inverse correlation between artery size and FMD% for the radial ( r = −0.66, P = 0.001), brachial ( r = −0.55, P = 0.01), and popliteal artery ( r = −0.48, P = 0.03), but not for the superficial and common femoral artery. Normalization of FMD responses for differences in eliciting shear rate did not abolish the between-artery relationship for artery function and size ( r = −0.48, P < 0.001), suggesting that differences between artery function responses were not entirely due to size-related differences in shear rate. This was reinforced by a significant between-artery correlation for GTN responses and baseline artery size ( r = −0.74, P < 0.001). In summary, systematic differences exist in vascular function responses of conduit arteries that differ in size. This raises the possibility that differences in artery size within or between individuals may influence functional responses.

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Photobiomodulation Improves the Inflammatory Response and Intracellular Signaling Proteins Linked to Vascular Function and Cell Survival in the Brain of Aged Rats

Molecular Neurobiology ◽

10.1007/s12035-021-02606-4 ◽

2021 ◽

Author(s):

Fabrízio dos Santos Cardoso ◽

Fernanda Cristina Borini Mansur ◽

Bruno Henrique Silva Araújo ◽

F. Gonzalez-Lima ◽

Sérgio Gomes da Silva

Keyword(s):

Inflammatory Response ◽

Cell Survival ◽

Intracellular Signaling ◽

Vascular Function ◽

Signaling Proteins ◽

Aged Rats ◽

The Brain

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Photobiomodulation Improves the Inflammatory Response and Intracellular Signaling Proteins Linked To Vascular Function and Cell Survival in the Brain of Aged Rats

10.21203/rs.3.rs-293139/v1 ◽

2021 ◽

Author(s):

Fabrizio Cardoso ◽

Fernanda Mansur ◽

Bruno Araújo ◽

Francisco Gonzalez-Lima ◽

Sérgio Gomes da Silva

Keyword(s):

Cerebral Cortex ◽

Inflammatory Response ◽

Cell Survival ◽

Laser Treatment ◽

Intracellular Signaling ◽

Vascular Function ◽

Signaling Proteins ◽

Aged Rats ◽

Cytokines And Chemokines ◽

Aged Brain

Abstract Photobiomodulation is a non-pharmacological tool widely used to reduce inflammation in many tissues. However, little is known about its effects on the inflammatory response in the aged brain. We conducted the study to examine anti-inflammatory effects of photobiomodulation in aging brains. We used aged rats (20 months old) with control (handled, laser off) or transcranial laser (660 nm wavelength, 100 mW power) treatments for 10 consecutive days and evaluated the level of inflammatory cytokines and chemokines, and the expression and activation of intracellular signaling proteins in the cerebral cortex and the hippocampus. Inflammatory analysis showed that aged rats submitted to transcranial laser treatment had increased levels of IL-1alpha and decreased levels of IL-5 in the cerebral cortex. In the hippocampus, the laser treatment increased the levels of IL-1alpha and decreased levels of IL-5, IL-18 and fractalkine. Regarding the intracellular signaling proteins, a reduction in the ERK and p38 expression and an increase in the STAT3 and ERK activation were observed in the cerebral cortex of aged rats from the laser group. In addition, the laser treatment increased the hippocampal expression of p70S6K, STAT3 and p38 of aged rats. Taken together, our data indicate that transcranial photobiomodulation can improve the inflammatory response and the activation of intracellular signaling proteins linked to vascular function and cell survival in the aged brain.

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High-Intensity Exercise Enhances Conduit Artery Vascular Function in Older Adults

Medicine & Science in Sports & Exercise ◽

10.1249/mss.0000000000001405 ◽

2018 ◽

Vol 50 (1) ◽

pp. 124-130 ◽

Cited By ~ 8

Author(s):

ERIKA IWAMOTO ◽

JOSHUA M. BOCK ◽

DARREN P. CASEY

Keyword(s):

Older Adults ◽

High Intensity ◽

Vascular Function ◽

High Intensity Exercise ◽

Conduit Artery

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ELTD1-deletion reduces vascular abnormality and improves T-cell recruitment after PD-1 blockade in glioma

Neuro-Oncology ◽

10.1093/neuonc/noab181 ◽

2021 ◽

Author(s):

Hua Huang ◽

Maria Georganaki ◽

Lei Liu Conze ◽

Bàrbara Laviña ◽

Luuk van Hooren ◽

...

Keyword(s):

T Cell ◽

Inflammatory Response ◽

Differentially Expressed Genes ◽

Vascular Function ◽

Patient Survival ◽

Vascular Dysfunction ◽

Treatment Resistance ◽

Differentially Expressed ◽

Vascular Abnormality

Abstract Background Tumor vessels in glioma are molecularly and functionally abnormal, contributing to treatment resistance. Proteins differentially expressed in glioma vessels can change vessel phenotype and be targeted for therapy. ELTD1 (Adgrl4) is an orphan member of the adhesion G-protein-coupled receptor family upregulated in glioma vessels, and has been suggested as a potential therapeutic target. However, the role of ELTD1 in regulating vessel function in glioblastoma is poorly understood. Methods ELTD1 expression in human gliomas and its association with patient survival was determined using tissue microarrays and public databases. The role of ELTD1 in regulating tumor vessel phenotype was analyzed using orthotopic glioma models and ELTD1 -/- mice. Endothelial cells isolated from murine gliomas were transcriptionally profiled to determine differentially expressed genes and pathways. The consequence of ELTD1-deletion on glioma immunity was determined by treating tumor bearing mice with PD-1-blocking antibodies. Results ELTD1 levels were upregulated in human glioma vessels, increased with tumor malignancy, and were associated with poor patient survival. Progression of orthotopic gliomas was not affected by ELTD1-deletion, however, tumor vascular function was improved in ELTD1 -/- mice. Bioinformatic analysis of differentially expressed genes indicated increased inflammatory response and decreased proliferation in tumor endothelium in ELTD1 -/- mice. Consistent with an enhanced inflammatory response, ELTD1-deletion improved T-cell infiltration in GL261-bearing mice after PD-1 checkpoint blockade. Conclusion Our data demonstrate that ELTD1 participates in inducing vascular dysfunction in glioma, and suggests that targeting of ELTD1 may normalize the vessels and improve the response to immunotherapy.

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Selective PDE1 inhibition ameliorates vascular function, reduces inflammatory response, and lowers blood pressure in ageing animals

Journal of Pharmacology and Experimental Therapeutics ◽

10.1124/jpet.121.000628 ◽

2021 ◽

pp. JPET-AR-2021-000628

Author(s):

Keivan Golshiri ◽

Ehsan Ataei Ataabadi ◽

Eloísa Rubio-Beltran ◽

Sophie Dutheil ◽

Wei Yao ◽

...

Keyword(s):

Blood Pressure ◽

Inflammatory Response ◽

Vascular Function

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Influence of spontaneously occurring bursts of muscle sympathetic nerve activity on conduit artery diameter

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00372.2013 ◽

2013 ◽

Vol 305 (6) ◽

pp. H867-H874 ◽

Cited By ~ 15

Author(s):

Seth T. Fairfax ◽

Jaume Padilla ◽

Lauro C. Vianna ◽

Seth H. Holwerda ◽

Michael J. Davis ◽

...

Keyword(s):

Sympathetic Nerve ◽

Vascular Function ◽

Regional Differences ◽

Sympathetic Nerve Activity ◽

Pressor Response ◽

Muscle Sympathetic Nerve Activity ◽

Nerve Activity ◽

Conduit Artery ◽

Spike Triggered Averaging ◽

Similar Peak

Large increases in muscle sympathetic nerve activity (MSNA) can decrease the diameter of a conduit artery even in the presence of elevated blood pressure, suggesting that MSNA acts to regulate conduit artery tone. Whether this influence can be extrapolated to spontaneously occurring MSNA bursts has not been examined. Therefore, we tested the hypothesis that MSNA bursts decrease conduit artery diameter on a beat-by-beat basis during rest. Conduit artery responses were assessed in the brachial (BA), common femoral (CFA) and popliteal (PA) arteries to account for regional differences in vascular function. In 20 young men, MSNA, mean arterial pressure (MAP), conduit artery diameter, and shear rate (SR) were continuously measured during 20-min periods of supine rest. Spike-triggered averaging was used to characterize beat-by-beat changes in each variable for 15 cardiac cycles following all MSNA bursts, and a peak response was calculated. Diameter increased to a similar peak among the BA (+0.14 ± 0.02%), CFA (+0.17 ± 0.03%), and PA (+0.18 ± 0.03%) following MSNA bursts (all P < 0.05 vs. control). The diameter rise was positively associated with an increase in MAP in relation to increasing amplitude and consecutive numbers of MSNA bursts ( P < 0.05). Such relationships were similar between arteries. SR changes following MSNA bursts were heterogeneous between arteries and did not appear to systematically alter diameter responses. Thus, in contrast to our hypothesis, spontaneously occurring MSNA bursts do not directly influence conduit arteries with local vasoconstriction or changes in shear, but rather induce a systemic pressor response that appears to passively increase conduit artery diameter.

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