Biomedical subjects

Anitaben Tailor

Publications and source records attributed to Anitaben Tailor.

6 recordsLinked to original sources

PubMed2003

HMG-CoA reductase inhibitor attenuates platelet adhesion in intestinal venules of hypercholesterolemic mice.

Whereas the anti-inflammatory properties of statins have been extensively studied, less attention has been devoted to the antithrombogenic effects of these drugs. We evaluated the effect of short-term (18 h) treatment with pravastatin (1 mg/kg) on hypercholesterolemia-induced platelet-endothelial (P/E) cell adhesion in intestinal venules. Mice were placed on either a normal diet (ND) or cholesterol-enriched diet (HCD) for 2 wk. Wild-type mice fed a HCD exhibited significantly elevated blood serum cholesterol levels, which were unaltered by pravastatin treatment. ND or HCD platelets were isolated, fluorescently labeled, and administered to either ND or HCD recipients. Intravital videomicroscopy was used to quantify transient (saltation) and firm adhesion of platelets. HCD mice receiving platelets from either ND or HCD mice exhibited increased P/E cell interactions compared with ND mice receiving platelets from ND or HCD mice. P/E adhesion was dramatically reduced when platelets from donor mice, recipient mice, or both were treated with pravastatin. The protective effect of pravastatin in hypercholesterolemia-induced P/E cell adhesion was abolished in N(G)-nitro-l-arginine methyl ester-treated mice. These results indicate that 1). hypercholesterolemia-induced P/E cell adhesion is mediated by changes in the vascular wall rather than circulating platelets; 2). pravastatin treatment inhibits the prothrombogenic effects of hypercholesterolemia via an action on both endothelial cells and platelets; and 3). the protective effect of pravastatin is nitric oxide dependent.

Animals↗

PubMed2003

Hypercholesterolemia promotes P-selectin-dependent platelet-endothelial cell adhesion in postcapillary venules.

OBJECTIVE: The objectives of this study were to determine whether hypercholesterolemia promotes platelet-endothelial cell (P/E) adhesion in murine postcapillary venules and define the contributions of endothelial or platelet associated P-selection to hypercholesterolemia-induced P/E interactions. METHODS AND RESULTS: Wild-type (WT) or P-selectin deficient (P-sel-/-) platelets were isolated and labeled with the fluorochrome CFSE and administered to either WT or P-sel-/- mice placed on a normal diet (ND) or high cholesterol diet (HCD). Intravital videomicroscopy was used to quantify platelet saltation and firm adhesion. HCD-WT mice exhibited a time-dependent increase in P/E cell interactions (relative to ND-WT). Flow cytometry revealed an increased expression of P-selectin on circulating platelets of HCD-WT mice at 2 weeks compared with ND-WT mice. When WT platelets were monitored in HCD-P-sel-/- mice, P/E adhesion was dramatically reduced. However, when P-sel-/- platelets were monitored in HCD-WT recipients, P/E adhesive interactions were reduced even further, comparable to ND-WT mice. CONCLUSIONS: These results indicate that elevated cholesterol levels promote P/E adhesion in postcapillary venules and that whereas both endothelial and platelet P-selectin contribute to hypercholesterolemia-induced recruitment of platelets, platelet-associated P-selectin seems to play a more important role in producing the prothrombogenic phenotype in venules.

Animals↗

PubMed2002

Hypercholesterolemia promotes inflammation and microvascular dysfunction: role of nitric oxide and superoxide.

Relatively brief periods (days) of hypercholesterolemia can exert profound effects on endothelium-dependent functions of the microcirculation, including dilation of arterioles, fluid filtration across capillaries, and regulation of leukocyte recruitment in postcapillary venules. Hypercholesterolemia appears to convert the normal anti-inflammatory phenotype of the microcirculation to a proinflammatory phenotype. This phenotypic change appears to result from a decline in nitric oxide (NO) bioavailability that results from a reduction in NO biosynthesis, inactivation of NO by superoxide (O(2)(*)(-)), or both. A consequence of the hypercholesterolemia-induced microvascular responses is an enhanced vulnerability of the microcirculation to the deleterious effects of ischemia and other inflammatory conditions. Hence, therapeutic strategies that are directed towards preventing the early microcirculatory dysfunction and inflammation caused by hypercholesterolemia may prove effective in reducing the high mortality associated with ischemic tissue diseases. Agents that act to maintain the normal balance between NO and reactive oxygen species (ROS) in vascular endothelial cells may prove particularly useful in this regard.

Animals↗

PubMed2002

Low venular shear rates promote leukocyte-dependent recruitment of adherent platelets.

The influence of reductions in venular shear rate on platelet-endothelial (P/E) cell adhesion has not been previously addressed. The objectives of this study were to define the effects of reductions in venular shear rate on P/E cell adhesion and to determine the interdependence of P/E cell adhesion and leukocyte-endothelial (L/E) cell adhesion at low shear rates. Intravital videomicroscopy was used to quantify P/E and L/E cell adhesion in rat mesenteric venules exposed to shear rates ranging between 118 +/- 9 and 835 +/- 44 s(-1). Shear rate was altered in postcapillary venules by rapid, graded blood withdrawal, without retransfusion of shed blood. Reducing shear rate from >600 s(-1) to <200 s(-1) resulted in an eightfold increase in L/E cell adhesion, whereas P/E cell adhesion increased 18-fold. A blocking antibody directed against P-selectin blunted both the P/E and L/E cell adhesion elicited by low shear rates. Immunoneutralization of CD11/CD18 on leukocytes or rendering animals neutropenic also blocked the shear rate-dependent recruitment of both platelets and leukocytes. These findings indicate that 1) low shear rates promote P/E and L/E cell adhesion in mesenteric venules, and 2) adherent neutrophils (mediated by CD11/CD18) create a platform onto which platelets can bind to the venular wall at low shear rates.

Animals↗

PubMedDate not supplied

Hypercholesterolemia promotes leukocyte-dependent platelet adhesion in murine postcapillary venules.

OBJECTIVE: Leukocyte-platelet aggregates form in blood during the development of cardiovascular diseases, including atherosclerosis. The study determined whether leukocytes contribute to the platelet adhesion induced by hypercholesterolemia in postcapillary venules. METHODS: Wild-type (WT) C57Bl/6 or CD18-deficient (CD18-/-) mice were placed on a normal (ND) or high-cholesterol (HC) diet for 2 weeks. Platelets isolated from ND, HC, or CD18-/- mice were fluorescently labeled with CFSE, and administered to either ND, HC, HC-CD18-/- or anti-neutrophil serum (HC-ANS)-treated mice. Rhodamine 6G was administered to label and visualize leukocytes. Intravital fluorescence microscopy was used to quantify leukocyte and platelet adhesion in intestinal postcapillary venules. RESULTS: HC increased both leukocyte and platelet adhesion (relative to ND). Greater than 50% of adherent platelets in HC mice were bound to adherent leukocytes. When HC platelets were examined in HC-ANS-treated or HC-CD18-/- mice, leukocyte-dependent platelet adhesion was significantly attenuated. Conversely, when HC-CD18-/- platelets were observed in HC recipients both leukocyte-dependent and endothelium-dependent platelet adhesion was comparable to HC mice receiving WT platelets. CONCLUSIONS: The findings demonstrate that the pro-thrombogenic phenotype assumed in the microvasculature during hypercholesterolemia is largely attributed to leukocyte-dependent platelet adhesion.

Animals↗

PubMedDate not supplied

Platelet-vessel wall interactions in the microcirculation.

Platelet adhesion in the microcirculation is being reported and studied in a growing number of animal models of human disease. The adhesion molecules utilized by platelets to attach to the walls of microscopic blood vessels have been defined in most model systems, with P-selectin-PSGL-1, GPIIb/IIIa-fibrinogen-ICAM-1, and vWF-GPIba interactions serving as major adhesion pathways. The binding of platelets to adherent leukocytes appears to contribute significantly to the platelet-vessel wall interactions elicited in many models of disease. Shear forces generated by the movement of blood through the microcirculation exert an important influence on platelet adhesion. Physiologic regulation of platelet adhesion is mediated by both nitric oxide and superoxide, with the former inhibiting and the latter promoting platelet adhesion. The interactions between platelets and the walls of microscopic blood vessels appear to have important implications in the initiation and/or progression of tissue injury associated with different experimental models of human disease.

Blood Platelets↗