scholarly journals Protection of Coronary Endothelial Function during Cardiac Surgery: Potential of Targeting Endothelial Ion Channels in Cardioprotection

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Qin Yang ◽  
Cheuk-Man Yu ◽  
Guo-Wei He ◽  
Malcolm John Underwood
Keyword(s):  
Endothelial Cells ◽  
Blood Flow ◽  
Cardiac Surgery ◽  
Ion Channels ◽  
Endothelial Function ◽  
Trp Channels ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Coronary Endothelial Function ◽  
Vasoactive Factors

Vascular endothelium plays a critical role in the control of blood flow by producing vasoactive factors to regulate vascular tone. Ion channels, in particular, K+channels and Ca2+-permeable channels in endothelial cells, are essential to the production and function of endothelium-derived vasoactive factors. Impairment of coronary endothelial function occurs in open heart surgery that may result in reduction of coronary blood flow and thus in an inadequate myocardial perfusion. Hyperkalemic exposure and concurrent ischemia-reperfusion during cardioplegic intervention compromise NO and EDHF-mediated function and the impairment involves alterations of K+channels, that is,KATPandKCa, and Ca2+-permeable TRP channels in endothelial cells. Pharmacological modulation of these channels during ischemia-reperfusion and hyperkalemic exposure show promising results on the preservation of NO and EDHF-mediated endothelial function, which suggests the potential of targeting endothelial K+and TRP channels for myocardial protection during cardiac surgery.

scholarly journals Ion channel networks in the control of cerebral blood flow

2015 ◽  
Vol 36 (3) ◽  
pp. 492-512 ◽  
Author(s):  
Thomas A Longden ◽  
David C Hill-Eubanks ◽  
Mark T Nelson
Keyword(s):  
Endothelial Cells ◽  
Blood Flow ◽  
Smooth Muscle ◽  
Cerebral Blood Flow ◽  
Ion Channels ◽  
Ion Channel ◽  
Vascular Endothelial Cells ◽  
Neurovascular Unit ◽  
Muscle Membrane ◽  
Neuronal Stimulation

One hundred and twenty five years ago, Roy and Sherrington made the seminal observation that neuronal stimulation evokes an increase in cerebral blood flow.1 Since this discovery, researchers have attempted to uncover how the cells of the neurovascular unit—neurons, astrocytes, vascular smooth muscle cells, vascular endothelial cells and pericytes—coordinate their activity to control this phenomenon. Recent work has revealed that ionic fluxes through a diverse array of ion channel species allow the cells of the neurovascular unit to engage in multicellular signaling processes that dictate local hemodynamics. In this review we center our discussion on two major themes: (1) the roles of ion channels in the dynamic modulation of parenchymal arteriole smooth muscle membrane potential, which is central to the control of arteriolar diameter and therefore must be harnessed to permit changes in downstream cerebral blood flow, and (2) the striking similarities in the ion channel complements employed in astrocytic endfeet and endothelial cells, enabling dual control of smooth muscle from either side of the blood–brain barrier. We conclude with a discussion of the emerging roles of pericyte and capillary endothelial cell ion channels in neurovascular coupling, which will provide fertile ground for future breakthroughs in the field.

scholarly journals Mechanisms of the protective effects of urocortin on coronary endothelial function during ischemia-reperfusion in rat isolated hearts

2005 ◽  
Vol 145 (4) ◽  
pp. 490-494 ◽  
Author(s):  
Angel Luis García-Villalón ◽  
Yesika María Amezquita ◽  
Luis Monge ◽  
Nuria Fernández ◽  
Belén Climent ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Ischemia Reperfusion ◽  
Protective Effects ◽  
Isolated Hearts ◽  
Coronary Endothelial Function

Urocortin Protects Coronary Endothelial Function During Ischemia-Reperfusion: A Brief Communication

2004 ◽  
Vol 229 (1) ◽  
pp. 118-120 ◽  
Author(s):  
Angel Luis García-Villalón ◽  
Elena Sanz ◽  
Luis Monge ◽  
Nuria Fernández ◽  
Belén Climent ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Ischemia Reperfusion ◽  
Coronary Endothelial Function

scholarly journals Randomized Trial of Anti-inflammatory Medications and Coronary Endothelial Dysfunction in Patients With Stable Coronary Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Allison G. Hays ◽  
Michael Schär ◽  
Gabriele Bonanno ◽  
Shenghan Lai ◽  
Joseph Meyer ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Primary Endpoint ◽  
Low Dose ◽  
Critical Role ◽  
Isometric Handgrip ◽  
Coronary Endothelial Function ◽  
Markers Of Inflammation ◽  
Anti Inflammatory ◽  
Stable Cad ◽  
The Impact

Aims: Inflammation plays a critical role in the pathogenesis of coronary artery disease (CAD), however the impact of anti-inflammatory therapies to reduce those processes which promote atherosclerosis in CAD patients is unknown. We aimed to test the hypothesis that anti-inflammatory approaches improve impaired coronary endothelial function (CEF), a driver of coronary atherosclerosis, in stable CAD patients.Methods and Results: We performed a single-center, randomized, placebo-controlled, double-blinded trial to assess whether low dose methotrexate (MTX), low dose colchicine (LDC), and/or their combination (MTX+LDC), improves CEF using non-invasive MRI measures in patients with stable CAD (N = 94). The primary endpoint was the MRI-detected change in coronary cross-sectional area from rest to isometric handgrip exercise (IHE), a predominantly nitric oxide-dependent endothelial dependent stressor. Coronary and systemic endothelial endpoints, and serum inflammatory markers, were collected at baseline, 8 and 24 weeks. Anti-inflammatory study drugs were well-tolerated. There were no significant differences in any of the CEF parameters among the four groups (MTX, LDC, MTX+LDC, placebo) at 8 or 24 weeks. Serum markers of inflammation and systemic endothelial function measures were also not significantly different among the groups.Conclusion: This is the first study to examine the effects of the anti-inflammatory approaches using MTX, LDC, and/or the combination in stable CAD patients on CEF, a marker of vascular health and the primary endpoint of the study. Although these anti-inflammatory approaches were relatively well-tolerated, they did not improve coronary endothelial function in patients with stable CAD.Clinical Trial Registration:www.clinicaltrials.gov, identifier: NCT02366091.

Abstract 11809: Trans-Endothelial Electrical Resistance to Assess Cell Layer Integrity in Coronary Artery Endothelial Cells After Hypoxia/Reoxygenation Injury

Circulation ◽  
2021 ◽  
Vol 144 (Suppl_2) ◽  
Author(s):  
Matthew J Hampton ◽  
Insha H Maknojia ◽  
zhu li ◽  
Matthew B Barajas ◽  
Matthias L Riess
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Coronary Artery ◽  
Electrical Resistance ◽  
Cell Layer ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Membrane Integrity ◽  
Cardiac Cells

Introduction: Cardiovascular disease remains one of the leading causes of complications and death worldwide. Therefore, accurate and reliable methods of mimicking ischemia/reperfusion (IR) injury in cardiac cells in vivo are crucial when testing drugs/substances for prevention and treatment. Coronary artery endothelial cells play a critical role in not only supplying blood to myocardial cells but protecting them from insult as well. However, the endothelial layer can be compromised by ischemic injury, heightening damage to the heart during reperfusion. Hypothesis: Varied ischemic insult of mouse coronary artery endothelial cells (MCAECs) affects cell layer integrity as measured by Trans-Endothelial Electrical Resistance (TEER). Methods: MCAECs were cultured on Grenier Bio-One ThinCert™-cell culture inserts for 72 hrs to allow for adequate confluency. Cells were then subjected to either continued normoxic conditions or hypoxia for 3, 6, 12, or 24 hrs, with a 2-hr reperfusion period immediately following. TEER was used to measure the integrity of the endothelial cell layer on the insert. Results: Our data showed a significant decrease in TEER between control and hypoxic groups after 6 hrs (p = 0.0400), 12 hrs (p = 0.0179) and 24 hrs (p = 0.0103), but not after 3 hrs (p = 0.4453) of hypoxia. Conclusion: This indicates that titrating the hypoxia time to a sufficient duration is necessary to achieve an adequate H/R injury which can then be used for potential cardioprotective agents and/or strategies to be tested. Furthermore, TEER is a reliable and reproducible method to assess the role of endothelial cell membrane integrity in cardioprotection.

Abstract P242: Perivascular Adipose Tissue Regulates Endothelial Function And Glucose Disposal Via Leptin Control Of The 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 / NADPH Oxidase 1 Pathways

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Reem T Atawia ◽  
Thiago B Bruder-nascimento ◽  
Tetsuo Horimatsu ◽  
Xueyi Li ◽  
Simone Kennard ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Adipose Tissue ◽  
Endothelial Function ◽  
Leptin Receptor ◽  
Critical Role ◽  
Underlying Mechanism ◽  
Glucose Disposal ◽  
Perivascular Adipose Tissue ◽  
Nadph Oxidase 1 ◽  
Signaling Activation

Our group has previously reported that lack of adipose tissue (lipodystrophy) leads to glucose intolerance and impaired endothelial-dependent vasorelaxation (EDR) via reduced signaling of the adipokine, leptin in the endothelium. However, the identity of the adipose depot responsible for endothelial leptin signaling activation and the underlying mechanism remains ill-defined. Our new data indicate that the perivascular adipose tissue (PVAT) is an important source of leptin. Thus, we hypothesized that leptin specifically derived from PVAT restores EDR and glucose tolerance in a mouse model with global deficiency in adipose tissue (lipodystrophic, BSCL2 -/- ). Restoration of PVAT in BSCL2 -/- mice corrected systemic glycemic status (GTT AUC, BSCL2 -/- + PVAT 635.3 ± 31.28 vs sham 741.6 ± 45.87, p<0.05). Moreover, PVAT transplantation restored EDR locally (abdominal aorta EDR AUC, BSCL2 -/- + PVAT 224.9 ± 23.97 vs 109 ± 19, P<0.05) but not systemically (thoracic aorta EDR AUC, BSCL2 -/- + PVAT 143.8 ± 22.29 vs sham 131.3 ± 11.54, P<0.05), indicating a distinctive paracrine role for PVAT-derived leptin in the vasculature. Concomitantly, we reported that inhibition of endothelial glycolysis, the main bioenergetic pathway of endothelial cells, via inhibition of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a major regulator of the glycolytic pathway, significantly improved endothelial function in both lipodystrophic mice and endothelial leptin receptor (LepR) deficient mice, as leptin does. Also, endothelial cells extracted from aortas of BSCL2 -/- mice showed a trend towards an increase in PFKFB3 mRNA expression compared to WT mice. Moreover, we found that overexpression of PFKFB3 in aortic rings and endothelial cells impaired EDR and increased the ROS generating enzyme, Nox1 expression, respectively. Collectively, our results showed the critical role of PVAT-driven leptin and endothelial leptin receptor signaling in regulating systemic glucose disposal as well as endothelial function via a mechanism that potentially regulates endothelial glycolysis and oxidative stress-mediated via PFKFB3/NOX1.

Coenzyme Q10 protects coronary endothelial function from ischemia reperfusion injury via an antioxidant effect

Surgery ◽  
1996 ◽  
Vol 120 (2) ◽  
pp. 189-196 ◽  
Author(s):  
Hitoshi Yokoyama ◽  
David M. Lingle ◽  
Juan A. Crestanello ◽  
Joseph Kamelgard ◽  
Brian R. Kott ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Reperfusion Injury ◽  
Coenzyme Q10 ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Antioxidant Effect ◽  
Coronary Endothelial Function

scholarly journals The Effect of Lower Limb Revascularization on Flow, Perfusion, and Systemic Endothelial Function: A Systematic Review

Angiology ◽  
2020 ◽  
pp. 000331972096954
Author(s):  
Pasha Normahani ◽  
Sodabeh Khosravi ◽  
Viknesh Sounderajah ◽  
Mohamed Aslam ◽  
Nigel J. Standfield ◽  
...  
Keyword(s):  
Blood Flow ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Lower Limb ◽  
Ischemia Reperfusion ◽  
Tissue Perfusion ◽  
Current Evidence ◽  
Limb Blood Flow ◽  
Flow Perfusion ◽  
The Impact

Peripheral arterial disease (PAD) is associated with reduced lower limb blood flow and tissue perfusion. The consequent reduction in vessel wall shear stress as well as ischemia–reperfusion injury has also been associated with systemic endothelial dysfunction and inflammation. We aimed to explore the impact of lower limb revascularization on (1) lower limb blood flow, (2) tissue perfusion, and (3) systemic endothelial function. We performed a systematic literature search using the MEDLINE, Embase, and Web of Science databases. Eligible studies measured changes in lower limb blood flow, perfusion, or systemic endothelial function following revascularization for the treatment of symptomatic PAD. We found 19 eligible studies, which were limited by considerable heterogeneity. Current evidence suggests that revascularization has a positive effect on flow, perfusion, and systemic endothelial dysfunction. Any changes may take a number of weeks to become apparent. There is a need for well-designed studies to explore the association between flow, perfusion, and endothelial dysfunction.

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