Hypercholesterolemia induces leukocyte entrapment in the retinal microcirculation of rats

Tomida, Kazuyuki; Tamai, Kazushi; Matsuda, Yoshito; Matsubara, Akiko; Ogura, Yuichiro

doi:10.1076/ceyr.23.1.38.5424

Cited by 16 publications

(9 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…9 Tomida et al showed that hypercholesterolemia itself induces leukocyte accumulation in the rat retina. 18 However, serum lipid levels are unchanged by pitavastatin administration in rats. It has also been reported that pitavastatin prevents NMDA-induced retinal ganglion cell death by suppressing leukocyte recruitment in rats.…”

Section: Discussionmentioning

confidence: 99%

Pitavastatin Attenuates Leukocyte-Endothelial Interactions Induced by Ischemia-Reperfusion Injury in the Rat Retina

Miyaki

Matsubara

Nishiwaki

et al. 2009

Current Eye Research

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Pitavastatin Attenuates Leukocyte-Endothelial Interactions Induced by Ischemia-Reperfusion Injury in the Rat Retina

Miyaki

Matsubara

Nishiwaki

et al. 2009

Current Eye Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…Chen et al (39) reported that dyslipidemia, not hyperglycemia, induces inflammatory adhesion molecules in human retinal vascular endothelial cells. In fact, leukocyte entrapment in the retinal microcirculation is enhanced in the early stage of hypercholesterolemia even in nondiabetic rats and was increased as the period of hypercholesterolemia was prolonged (6).…”

Section: Fig 5 Linear Regression Analysis Of Polymorphonuclear Leukmentioning

confidence: 96%

“…Leukocyte entrapment in the retinal microcirculation was enhanced in the early stage of hypercholesterolemia even in nondiabetic rats (6). Dyslipidemia has been associated with endothelial dysfunction and impaired vasodilatory response, and postprandial hypertriglyceridemia is exaggerated in type 2 diabetes (7).…”

mentioning

confidence: 99%

Neutrophils Are Associated With Capillary Closure in Spontaneously Diabetic Monkey Retinas

et al. 2005

View full text Add to dashboard Cite

Type 2 diabetes develops spontaneously in obese aging rhesus monkeys (Macaca mulatta). This study investigates the association between polymorphonuclear leukocytes and development of retinopathy. Blood pressure and plasma glucose levels were determined in 15 diabetic and 6 nondiabetic monkeys. The plasma levels of total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides were determined just before the start of the animal's final decline and elective necropsy. Retinas were incubated for ADPase (labels viable retinal blood vessels) and nonspecific esterase (labels neutrophils) activities. Polymorphonuclear leukocytes were counted per millimeter squared of retina. After the retina was flat-embedded in glycol methacrylate, tissue sections were taken through areas of interest and observed microscopically. Elevated numbers of intravascular polymorphonuclear leukocytes were present adjacent to areas with retinal capillary nonperfusion. There were significantly more polymorphonuclear leukocytes per millimeter squared in diabetic retinas (6.91 ؎ 5.01) compared with normal retinas (1.45 ؎ 1.62, P ‫؍‬ 0.018). Severity of hypertension in diabetes was also significantly associated with greater numbers of polymorphonuclear leukocytes (P ‫؍‬ 0.02). There was a significant positive exponential correlation between the number of polymorphonuclear leukocytes per millimeter squared and the level of total cholesterol (R ‫؍‬ 0.907), LDL cholesterol (R ‫؍‬ 0.875), the total cholesterol-to-HDL cholesterol ratio (R ‫؍‬ 0.86), and total triglycerides (R ‫؍‬ 0.888). This study demonstrates that severity of diabetes and the development of retinopathy are associated with increased numbers of polymorphonuclear leukocytes in the retina of diabetic monkeys. Hypertension, high plasma levels of LDL cholesterol and triglycerides, and low plasma levels of HDL cholesterol also are associated with increased polymorphonuclear leukocytes in retina. Diabetes 54:1534 -1542, 2005 A n early event in diabetic retinopathy is retinal capillary nonperfusion. Recent evidence suggests that leukocytes may initiate vaso-occlusion in diabetic retinal microvasculature (1). Miyamoto et al. (2) and Ogura (3) used acridine orange labeling and a scanning laser ophthalmoscope to observe leukocytes in diabetic rats. The number of leukocytes trapped in the retinal microcirculation was significantly elevated in streptozotocin-induced diabetic rats (2.5-fold) and Otsuka Long-Evans Tokushima Fatty (OLETF) rats (2-fold) in the early stages of diabetes compared with nondiabetic rats. They hypothesized that accumulation of leukocytes in diabetic retinas during the preretinopathy stage could cause microvascular occlusions and dysfunction, in turn causing retinopathy. Barouch et al. (4) later demonstrated that the increase in leukocyte accumulation or leukostasis was dependent on the adhesion molecule responsible for modulating firm adherence of leukocytes to endothelial cells, intracellular adhesion molecule-1 (ICAM-1), which is elevated in human diabetic retina (...

show abstract

“…Conceivably, conformational activity of FPRs and CD18 integrins, both of which have been reported to exhibit shear sensitivity for neutrophils, may be influenced by membrane cholesterol levels that potentially interfere with mechanotransduction processes [138]. Moreover, there is substantial evidence [58,60,[147][148][149] demonstrating a relationship between hypercholesterolemia and enhanced leukocyte activity in the microcirculation. Thus, similar to the case for hypertension, elevated leukocyte activity in the microcirculation may be linked to microvascular dysfunction and impaired tissue perfusion.…”

Section: Impaired Neutrophil Shear Response and Microvascular Dysfuncmentioning

confidence: 99%

Impaired Neutrophil Mechanoregulation by Fluid Flow: A Potential Contributing Factor for Microvascular Dysfunction in Obesity

Akenhead

Zhang

Shin

2014

The Mechanobiology of Obesity and Related Diseases

View full text Add to dashboard Cite

In this chapter, we discuss evidence that potentially implicates impaired neutrophil responses to shear stress as a putative factor in obesity-related cardiovascular disease. We do so by presenting evidence connecting obesity with microvascular disorders due to chronic inflammation and highlighting this link in the setting of hypertension and hypercholesterolemia. Furthermore, the potential impact of neutrophils on these obesity-related disease processes is discussed. Notably, both hypertension and hypercholesterolemia are associated with a deficiency in the neutrophil responsiveness to fluid shear stress. In this regard, we define the neutrophil responses to shear stress exposure and how these responses may play a role in microvascular function under physiological conditions as well as how their impairment may result in microcirculatory dysfunction. Finally, we point to data consistent with an impaired neutrophil shear sensitivity being a manifestation of obesity, particularly as it relates to hypertension and hypercholesterolemia. In this regard, we aim to suggest a novel perspective; specifically, that impaired neutrophil shear sensitivity precedes a chronic inflammatory state and serves as a putative source of obesity-related pathobiology.

show abstract

Hypercholesterolemia induces leukocyte entrapment in the retinal microcirculation of rats

Cited by 16 publications

References 19 publications

Pitavastatin Attenuates Leukocyte-Endothelial Interactions Induced by Ischemia-Reperfusion Injury in the Rat Retina

Pitavastatin Attenuates Leukocyte-Endothelial Interactions Induced by Ischemia-Reperfusion Injury in the Rat Retina

Neutrophils Are Associated With Capillary Closure in Spontaneously Diabetic Monkey Retinas

Impaired Neutrophil Mechanoregulation by Fluid Flow: A Potential Contributing Factor for Microvascular Dysfunction in Obesity

Contact Info

Product

Resources

About