Lack of Hemodynamic Forces Triggers Apoptosis in Vascular Endothelial Cells

Kaiser, D.; Freyberg, Mark-André; Friedl, Peter

doi:10.1006/bbrc.1997.6146

Cited by 149 publications

(99 citation statements)

References 25 publications

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“…With the increase of Hct, the RBC column expands, which in turn decreases the size of the plasma layer, causing erythrocytes to more effectively interact with endothelial cells, leading to increased shear stress and thus stimulation of NO release. Shear stress is essential to maintain endothelial cell integrity and functioning, and decreased shear stress can lead to apoptosis (7,19). Because cardiovascular diseases have been shown to be accompanied by endothelial dysfunction, it could be of clinical interest to focus on patients' Hct levels, given the importance of Hct in generating shear stress.…”

Section: Discussionmentioning

confidence: 99%

Paradoxical hypotension following increased hematocrit and blood viscosity

Martini¹,

Carpentier²,

Negrete³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

106

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-Hematocrit (Hct) of awake hamsters and CD-1 mice was acutely increased by isovolemic exchange transfusion of packed red blood cells (RBCs) to assess the relation between Hct and blood pressure. Increasing Hct 7-13% of baseline decreased mean arterial blood pressure (MAP) by 13 mmHg. Increasing Hct above 19% reversed this trend and caused MAP to rise above baseline. This relationship is described by a parabolic function (R 2 ϭ 0.57 and P Ͻ 0.05). Hamsters pretreated with the nitric oxide (NO) synthase (NOS) inhibitor N -nitro-L-arginine methyl ester (L-NAME) and endothelial NOS-deficient mice showed no change in MAP when Hct was increased by Ͻ19%. Nitrate/nitrite plasma levels of Hct-augmented hamsters increased relative to control and L-NAME treated animals. The blood pressure effect was stable 2 h after exchange transfusion. These findings suggest that increasing Hct increases blood viscosity, shear stress, and NO production, leading to vasodilation and mild hypotension. This was corroborated by measuring A1 arteriolar diameters (55.0 Ϯ 21.5 m) and blood flow in the hamster window chamber preparation, which showed statistically significant increased vessel diameter (1.04 Ϯ 0.1 relative to baseline) and microcirculatory blood flow (1.39 Ϯ 0.68 relative to baseline) after exchange transfusion with packed RBCs. Larger increases of Hct (Ͼ19% of baseline) led blood viscosity to increase Ͼ50%, overwhelming the NO effect through a significant viscosity-dependent increase in vascular resistance, causing MAP to rise above baseline values. nitric oxide; shear stress; vascular resistance; hypertension IT IS A GENERAL MEDICAL and clinical perception that an increase in blood viscosity may lead to short-and long-term negative physiological conditions, and there appears to be universal agreement that increased blood viscosity is a factor in hypertension. Lowering blood viscosity, however, is not advocated as a means for controlling hypertension with the exception of erythrocytosis, substantial Hct increases consequent to adaptation to high altitudes, and cardiovascular impairment in premature infants. These conditions represent extremes of an increase in blood viscosity and clearly must be corrected by lowering Hct, because the extreme excess of red blood cells (RBCs) is superfluous in providing adequate oxygen-carrying capacity and is in fact a hindrance to blood flow and therefore oxygen delivery.Clinical studies (14, 37) report a significant relationship between hypertension and high Hct levels. Hypertensive patients have higher Hct values than normotensive control individuals (23). Patients suffering from polycythemia vera or other erythrocytoses present with pathologically high Hcts leading to hypertension, thromboembolism, and other severe clinical complications (2, 15). There is evidence, however, that individuals, such as Peruvian miners, survive with Hct levels of 75-91% (18), suggesting the existence of an adaptive mechanism.Endothelial cells play a key role in the regulation of blood pressure and blood flow beca...

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Section: Discussionmentioning

confidence: 99%

Paradoxical hypotension following increased hematocrit and blood viscosity

Martini¹,

Carpentier²,

Negrete³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

106

View full text Add to dashboard Cite

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“…A link between mechanical stimulation and cell survival or death has been therefore suggested by several groups. Indeed, human umbilical vein endothelial cells (HUVEC) cultured under static conditions undergo a basal level of apoptosis (Kaiser et al, 1997). The empty space left between cells induces proliferation of adjacent cells so that an equilibrium state is reached with low levels of apoptosis and proliferation.…”

Section: Survival Pathwaysmentioning

confidence: 99%

“…The empty space left between cells induces proliferation of adjacent cells so that an equilibrium state is reached with low levels of apoptosis and proliferation. Exposure to¯ow in a perfusion chamber or in an ex vivo organ culture directly inhibits the apoptotic process and indirectly suppresses proliferation, leading to a`truly' quiescent monolayer (Kaiser et al, 1997).…”

Section: Survival Pathwaysmentioning

confidence: 99%

Apoptosis in the vasculature: mechanisms and functional importance

Mallat¹,

Tedgui²

2000

British J Pharmacology

304

214

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Apoptotic death has now been recognized in a number of common and threatening vascular diseases, including atherosclerosis. Interest in apoptosis research relates to the fact that apoptosis, in contrast to oncosis, is a highly regulated process of cell death which raises the hope for the development of speci®c therapeutic strategies to alter disease progression. This review summarizes the mechanisms involved in vascular endothelial and smooth muscle cell survival/apoptosis, and the potential roles of apoptotic death in atherosclerosis and restenosis. The potential e ects of modulation of apoptosis in these diseases are also discussed.

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“…29) Excessively low WSS within the aneurysm dome could promote various mechanisms that cause degradation of the aneurysm wall which could ultimately lead to rupture. 1,2,5,14,24) High values of WSSG indicate regions with high spatial changes in the WSS magnitude; these are typically regions of flow detachment and stagnation points. 15) A combination of high WSS and positive WSSG represents dangerous hemodynamics likely to induce aneurysm remodeling.…”

Section: Discussionmentioning

confidence: 99%

Changes in Hemodynamics After Placing Intracranial Stents

Ishida

Miura

Umeda

et al. 2013

Neurol. Med. Chir.(Tokyo)

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Stent-assisted coil embolization has enabled the endovascular treatment of wide-necked cerebral aneurysms. Moreover, recent reports demonstrated that stent-assisted coil embolization was associated with a significant decrease in angiographic recurrences of coiled cerebral aneurysms. One of the possible explanations for this adjunctive effect of stent-assisted coil embolization is changes in the local hemodynamics caused by placing intracranial stents. This study investigated the hemodynamic effect of intracranial stents using computational fluid dynamics (CFD) analysis. The geometry of the intracranial stent, Enterprise TM VRD, was acquired by using micro computed tomography and virtually placed across the aneurysm orifice of a saccular aneurysm model (saccular model) and a blister-like aneurysm model (blister-like model) constructed from patient-specific three-dimensional (3D) rotational angiography data. Transient CFD analysis was performed with these models with and without stents. Stent placement induced no significant changes in the 3D streamline in the saccular model and slight changes in the blister-like model. Both saccular and blister-like models with stents had lower wall shear stress (WSS) and flow velocity, and higher oscillatory shear index, WSS gradient, and relative residence time than the equivalent models without stents, indicating the possibility that stent placement induced stagnant and disturbed blood flow. Cross-sectional vector velocity around the stent strut revealed complex blood flow patterns with variable direction and velocity. Although this study was a simulation under limited conditions, similar hemodynamic changes might be induced in the neck remnants treated with stent-assisted coil embolization.

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Lack of Hemodynamic Forces Triggers Apoptosis in Vascular Endothelial Cells

Cited by 149 publications

References 25 publications

Paradoxical hypotension following increased hematocrit and blood viscosity

Paradoxical hypotension following increased hematocrit and blood viscosity

Apoptosis in the vasculature: mechanisms and functional importance

Changes in Hemodynamics After Placing Intracranial Stents

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