RESUMEN
Combined action of irradiation (IR), shear stress, and high blood pressure is well recognized to induce damage to vasculature, while data on pathological effects of IR in large peripheral vessels with low blood pressure are scarce. The purpose of the present study was hence to investigate time- and dose-dependent effects of local IR on inflammatory and prothrombotic processes in the Arteria (A.) saphena of C57BL/6 wild-type and apolipoprotein E (ApoE)-knockout mice. Single doses of 2, 5, 8, 10, or 16 Gy were locally delivered to the A. saphena of the left leg of the animals. The expression of CD31, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, monocyte chemoattractant protein-1 (MCP-1), and thrombomodulin (TM) was quantified by semiautomatic TissueFax fluorescence analysis in frozen arterial sections. Follow-up periods were 3, 6, 9, 12, or 18 months. Protein expression in the arterial wall displayed dose-dependent changes. Proinflammatory reactions were observed for CD31, E-selectin, ICAM, and VCAM already at doses of 2 Gy. Anti-inflammatory changes were detected for MCP-1 and TM. The effects were more pronounced in wild-type versus ApoE(-/-) mice. Changes remain mostly transient up to 16 Gy. Dose- and time-dependent changes in inflammatory and thrombotic mediators in the wall of the A. saphena were found after local IR but did not transform into histopathological consequences.
Asunto(s)
Apolipoproteínas E/deficiencia , Apolipoproteínas E/genética , Arterias/metabolismo , Arterias/efectos de la radiación , Regulación de la Expresión Génica/efectos de la radiación , Animales , Biomarcadores/metabolismo , Inflamación/metabolismo , Ratones , Ratones Noqueados , Factores de TiempoRESUMEN
Two-dimensional echocardiography (2-D echo) was performed in 86 consecutive patients with mitral valve prolapse (MVP) and in 25 normal subjects. In normal subjects, mitral leaflet thickness was 3.5 +/- 0.8 mm (mean +/- standard deviation) and the mitral leaflet thickness to aortic wall thickness ratio was 1.0 +/- 0.2. Patients with MVP were separated into 2 groups: those with normal mitral thickness (less than or equal to mean + 2 SD observed in normal subjects, i.e., less than or equal to 5.1 mm) and normal mitral thickness to aortic wall thickness ratio (less than or equal to mean + 2 SD observed in normal subjects, i.e., less than or equal to 1.4) (group I) and others in whom these values were increased (group II). In group I, mitral thickness was 3.6 +/- 0.6 mm and mitral thickness to aortic wall thickness ratio was 1.1 +/- 0.1, and in group II, mitral thickness was 8.8 +/- 1.2 mm and mitral thickness to aortic wall thickness ratio was 2.2 +/- 0.5. The only significant cardiovascular abnormalities in group I were mitral regurgitation in 2 patients and tricuspid valve prolapse in 1 patient. In group II, 7 patients had clinically significant mitral regurgitation, 8 had aortic root abnormalities, 4 had tricuspid valve prolapse and 6 had Marfan's syndrome. Cardiovascular abnormalities were present in 60% (18 of 30) of patients in group II and in 6% (3 of 56) of patients in group I (p less than 0.001). Two-dimensional echo enabled the identification of a subset of patients with MVP who had thickened mitral leaflets. These patients had an increased incidence of cardiovascular abnormalities.