Effects of Shear Stress on the Gene Expressions of Endothelial Nitric Oxide Synthase, Endothelin-1, and Thrombomodulin in Human Retinal Microvascular Endothelial Cells

Ishibazawa, Akihiro; Nagaoka, Taiji; Takahashi, Tatsuhisa; Yamamoto, Kimiko; Kamiya, Akira; Ando, Jun; Yoshida, Akitoshi

doi:10.1167/iovs.11-7686

Cited by 67 publications

(60 citation statements)

References 41 publications

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“…22 In an endothelial cell culture experiment, Ishibazawa et al showed that decreased shear rate is able to modulate endothelial gene expression including decreased thrombomodulin and decreased endothelial nitric oxide along with increased endothelin-1, with an overall effect of vasoconstriction and prothrombogenic endothelial profile. 33 Overall, the low shear rate seen in our patients compared to controls is consistent with highly abnormal endothelial function in these poorly controlled diabetics, which would severely compromise their response to laser therapy as well as their overall clinical outcomes.…”

Section: Discussionsupporting

confidence: 69%

Pilot Study of Doppler Optical Coherence Tomography of Retinal Blood Flow Following Laser Photocoagulation in Poorly Controlled Diabetic Patients

Lee

Wong

Tan

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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Section: Discussionsupporting

confidence: 69%

Pilot Study of Doppler Optical Coherence Tomography of Retinal Blood Flow Following Laser Photocoagulation in Poorly Controlled Diabetic Patients

Lee

Wong

Tan

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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“…21 The laminar flow is associated with shear stress, which is important for regulating blood flow. 22,23 The DOCT flowmeter can visualize the retinal blood velocity profile (RBVP), which is the velocity profile of the red blood cells in the horizontal center of a vessel at a given moment (Fig. 1C).…”

Section: Discussionmentioning

confidence: 99%

Repeatability and Reproducibility of Retinal Blood Flow Measurement Using a Doppler Optical Coherence Tomography Flowmeter in Healthy Subjects

Tani

Song

Yoshioka

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To evaluate the repeatability and reproducibility of retinal blood flow (RBF) measurements in humans by using new auto-alignment and measurement software in a commercially available Doppler optical coherence tomography (DOCT) system. METHODS.The DOCT flowmeter assessed the intrasession repeatability and the intersession and interobserver reproducibility of the RBF measurements. For intrasession repeatability, the coefficients of variation (CVs) of five repeated RBF measurements were calculated at the retinal arteries and veins in 20 normal eyes of 20 healthy volunteers. For intersession reproducibility, two sets of three measurements obtained by one observer on 2 different days were compared. For interobserver reproducibility, two sets of three measurements obtained by two observers on the same day were compared. Intraclass correlation coefficients (ICCs) also were used to evaluate the repeatability and reproducibility. The relevance of the DOCT flowmeter and laser Doppler velocimetry (LDV) also was assessed.RESULTS. Regarding intrasession repeatability, the ICC of the RBF exceeded 0.90 in arterioles and venules (ICC: 0.994 and 0.970, respectively). The CVs of the RBF in the arterioles and venules were 6.0% 6 3.4% and 8.8% 6 5.1%, respectively. The intersession and interobserver RBF values had high reproducibility in the arterioles (ICC: 0.980 and 0.993, respectively) and venules (ICC: 0.982 and 0.986, respectively). The RBF measured with the DOCT flowmeter was correlated strongly with LDV in the arterioles (r ¼ 0.76; P < 0.001).CONCLUSIONS. The DOCT flowmeter had good reproducibility in the arterioles and venules and precisely measured the RBF as compared to the LDV in the arterioles.

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“…In retinal endothelial cells, continuous laminar shear stress upregulates the expression of TM in a time-and dose-dependent manner [49]. Some studies have nonconsistently shown decreased endothelial TM expression upon cyclic strain [8].…”

Section: Tm In Mhtmentioning

confidence: 99%

Thrombomodulin and Endothelial Dysfunction: A Disease-Modifier Shared between Malignant Hypertension and Atypical Hemolytic Uremic Syndrome

Demeulenaere

Devreese

Vanbelleghem

et al. 2018

Nephron

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Thrombomodulin (TM) is an endothelial glycoprotein that is present in all blood vessels. Five percent of all patients with atypical hemolytic uremic syndrome (aHUS) have mutations in the gene coding for TM, with a peak presentation in young children. Mutations often translate into quantitative and qualitative abnormalities of this endothelial glycoprotein. Outcome of the TM-associated aHUS is relatively poor with frequent relapses after transplantation despite its membrane-bound character. We observed a woman presenting with malignant hypertension (MHT) and associated kidney, brain, cardiac, and hematological involvement with thrombotic microangiopathy on kidney biopsy. She had a documented mutation of the gene coding for TM, which was associated with both aHUS and an increased risk for venous and arterial thrombosis. As TM has anti-coagulant, anti-inflammatory, and cytoprotective properties and also attenuates alternative complement activation, this glycoprotein could play an active role in other diseases with endothelial involvement apart from aHUS. We discuss the potential role of TM in the pathophysiology of various endotheliopathies including MHT. We also provide a framework for future therapeutic options.

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Effects of Shear Stress on the Gene Expressions of Endothelial Nitric Oxide Synthase, Endothelin-1, and Thrombomodulin in Human Retinal Microvascular Endothelial Cells

Cited by 67 publications

References 41 publications

Pilot Study of Doppler Optical Coherence Tomography of Retinal Blood Flow Following Laser Photocoagulation in Poorly Controlled Diabetic Patients

Pilot Study of Doppler Optical Coherence Tomography of Retinal Blood Flow Following Laser Photocoagulation in Poorly Controlled Diabetic Patients

Repeatability and Reproducibility of Retinal Blood Flow Measurement Using a Doppler Optical Coherence Tomography Flowmeter in Healthy Subjects

Thrombomodulin and Endothelial Dysfunction: A Disease-Modifier Shared between Malignant Hypertension and Atypical Hemolytic Uremic Syndrome

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