RESUMO
We have studied the influence of new N,N'-substituted piperazines with variable nature of the linker between piperazine and aromatic cycles (carbonyl group in VR-0411 versus sulfonyl group in VR-0511) on thrombin-induced platelet aggregation, cytoplasmic Ca2+ mobilization in platelets, and P-selectin exposure on the platelet plasma membrane. The inhibitory effect of VR-0511 on platelet aggregation exceeds the effects of the reference compound aspirin and VR-0411 by 35 and 42%, respectively (p < or = 0.01). The effects of test compounds on the mobilization of cytoplasmic Ca2+ in platelets and P-selectin exposure indicate that VR-0411 and VR-0511 inhibit platelet activation in these tests by 28 and 61%, (p < or = 0.01) and 34 and 58% (p < or = 0.01), respectively. The possible targets for VR-0411 and VR-0511 are thromboxane and inositol triphosphate-dependent (IP3 formation) pathways of activation signal transfer.
Assuntos
Plaquetas/efeitos dos fármacos , Piperazinas/farmacologia , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Trombina/farmacologia , Adulto , Aspirina/farmacologia , Plaquetas/citologia , Plaquetas/metabolismo , Cálcio/metabolismo , Feminino , Expressão Gênica , Humanos , Fosfatos de Inositol/metabolismo , Masculino , Selectina-P/genética , Selectina-P/metabolismo , Piperazinas/síntese química , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/síntese química , Transdução de Sinais , Tromboxanos/metabolismoRESUMO
We examined 41 patients with ischemic heart disease (n=26) and dilated cardiomyopathy (DCM) (n=15). Control group comprised 15 practically healthy subjects. We found no substantial differences in the presence of CD34+CD133- and CD34+CD133-VEGFR-2+ cells in peripheral blood of patients with chronic heart failure (CHF) but noted lowering of level of CD34-CD133+VEGFR-2+ cells mainly in DCM group. Most significant factors determining lowering of number of circulating endothelial precursor cells (EPC) were age, level of low density lipoprotein cholesterol, and intima media thickness of common carotid arteries. We found lowering of colony forming ability of EPC in patients with CHF first of all in the group of patients with DCM. Abnormality of qualitative and quantitative composition of EPC can be considered as one of risk factors of endothelial dysfunction, pathological remodeling of cardiovascular system and CHF progression.
Assuntos
Cardiomiopatia Dilatada/patologia , Células Endoteliais/patologia , Células-Tronco Hematopoéticas/patologia , Isquemia Miocárdica/patologia , Adulto , Cardiomiopatia Dilatada/sangue , Doença Crônica , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/sangueRESUMO
We assessed effect of therapy with HMG--CoA reductase inhibitor rosuvastatin on the number of circulating hemopoietic stem CD34+, CD133+ cells in peripheral blood of patients with systolic left ventricular dysfunction of ischemic genesis. Number of circulating hemopoietic stem CD34+, CD133+ cells in patients with chronic heart failure did not differ from their number in control group, however we revealed tendency to increase of number of endothelial CD34+, CD133+, VEGFR-2+ progenitor cells. We confirmed presence of relationship between quantity of circulating stem and progenitor cells and traditional risk factors of cardiovascular events: age, excessive body mass, arterial hypertension, and intima media thickness of common carotid arteries. Besides lipid lowering effect therapy with rosuvastatin was associated with lowering of C-reactive protein level and increase of number of circulating CD34+, CD133+ cells.
