Increased leukocyte aggregation in patients with hypercholesterolaemia

Hypercholesterolemia induces leukocyte entrapment in the retinal microcirculation of rats

“…§ : P < 0.01. also detected in other studies. [21][22][23] Stragliotto et al observed a discrete number of morphologically abnormal monocytes and macrophages in the bloodstream of familial hypercholesterolemic patients. 21 Lechi et al suggested that the increased levels of plasma cholesterol might induce an intrinsic cellular membrane abnormality, because of an alteration of cholesterol-phospholipid ratio, which was responsible for the increased leukocyte aggregation.…”

“…21 Lechi et al suggested that the increased levels of plasma cholesterol might induce an intrinsic cellular membrane abnormality, because of an alteration of cholesterol-phospholipid ratio, which was responsible for the increased leukocyte aggregation. 22 Moreover, expression of an adhesion molecule, CD11b is reportedly related to increased leukocyte adhesion in hypercholesterolemia. 23 Thus, alterations of both endothelium and leukocytes including up-regulation of various adhesion molecules are considered responsible for increased leukocyte entrapment in the retinal microcirculation under hypercholesterolemia.…”

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

“…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.…”

Linking the Pathobiology of Hypercholesterolemia with the Neutrophil Mechanotransduction

“…For example, neutrophils with increased membrane cholesterol exhibit enhanced tethering and firm arrest on activated endothelial cell monolayers [41,71,72]. Moreover, neutrophils exposed to hypercholesterolemia display increased heterotypic adhesion to platelets [73] as well as increased homotypic aggregation in response to 10 M N-formyl-Met-Leu-Phe (fMLP) [74]. These studies confirm that cholesterol-dependent modulation of adhesion molecule expression has an impact on neutrophil adhesion to other leukocytes, platelets, or the endothelium lining the blood vessel lumen.…”

“…hypercholesterolemia and diabetes [74,140]. The critical issues are to increase efforts to define the link between chronic inflammation and impaired neutrophil mechanotransduction and to determine if chronic inflammation precedes or results from an impairment of vascular mechanotransduction.…”