P.047 CCR5-DEL32 GENOTYPE MODIFIES PRO-INFLAMMATORY//ANTI-INFLAMMATORY CYTOKINE RATIO; POSSIBLE ROLE IN ATHEROGENESIS
H. Moattar, G. Foteinos, K. Mandel, B. Zal, A. Weerasinghe, S. Fredricks, M. Jahangiri, N.D. Carter, A. Afzal
Integrin a1 knockout mice (a1-/-) were used to investigate the role of the integrin a1b1 in the cardiac and vascular functions of angiotensin II (AngII)-induced hypertension. Carotid artery (CA) elasticity was measured by incremental elastic modulus (Einc)-wall stress curves using an ultrasonic echo-tracking device and the measurement of medial cross-sectional area (MCSA) to evaluate in vivo CA mechanical properties. Cardiac function was studied by echocardiography in anaesthetized animals.
... sion of Ang II (200ng/kg/min) in a1-/mice and their control (a1+/+) for 4 weeks led to similar hypertensive effect (SAP +31 vs +37 mmHg). In a1-/-Ang II failed to increase MCSA of CA whereas it did in a1+/+ mice. The Einc-stress curve of Ang II-treated a1-/was shifted to the right compared to Ang II-treated a1+/+, indicating a decreased arterial stiffness. The a1+/+ had an increased cardiac hypertrophy, evaluated by an increase of the end diastolic thickness of the septum (IVSd: 1.2±1 vs 0.9±0.08 mm) without modification of the posterior wall (LVPWd: 0.10±0.6 vs 0.97±0.07 mm) and without dilation of the ventricular cavity. This septal hypertrophy was not found in the a1-/mice in response to Ang II. Cardiac fibrosis measured by collagen quantification (total, and type I and III), was lower in the a1-/mice, compared with the a1+/+. In conclusion, our results show an impaired of cardiovascular response to Ang II-induced hypertension in the integrin a1 knockout mouse. These results suggest the involvement of this integrin in the cardiovascular effects of Ang II. P.045 Background: Successful RTx from living-related donors, by removal of the uremic milieu and improvement in cardiovascular risk factors can be associated with improvement in indices of arterial stiffness. The aim of this study was to assess the arterial stiffness after one year of follow-up in live related RTx patients. Methods: The augmentation index (AIx) was determined from arterial waveforms contour analysis recorded by applanation tonometry using SphygmoCor ® device in 31 living related RTx (19 M, age 34.6±8.5 yrs; RTx duration 29.7±24.8 Mo, mean Cr.Cl. = 69.2±1.2 ml/min). All studies were performed before CsA administration, at baseline and at one-year follow-up. As a surrogate marker of the pulse wave velocity (PWV) we used the time to shoulder (TTS) parameter on the reconstructed central pulse pressure contour wave. Results: Overall, during follow-up, mean AIx increased from 13.5±13.3% to 15.6±10.5% (p = NS). TTS increased from 107.7±9.5 ms at baseline to 109.3±9.5 ms at follow-up (p = NS). Biochemical parameters, blood pressure and heart rate remained unchanged over the follow-up period. On univariate analysis, at both moments, AIx and TTS correlated with anthropometric parameters (height and weight) and serum creatinine (independent predictor at baseline R 2 = 0.443; p < 0.05). There was no correlation of the arterial stiffness parameters with creatinine clearance or CsA therapy (dosage/levels). Conclusions: In our study we demonstrate that there are no significant overall changes in arterial stiffness properties after one-year follow-up in stable renal transplant patients.