The metabolism of Phe-Pro was investigated in Caco-2 cell monolayers, a model of small intestinal epithelium. The results indicate that the majority of Phe-Pro was hydrolyzed during passage from the apical (AP) to basolateral (BL) side. The enzyme responsible for the hydrolysis is prolidase, a cytosolic enzyme. Through kinetic studies of a supernatant enzyme preparation, a Km of 30.4 microM and Vmax of 38.9 nmol/min per mg of protein were obtained. The enzyme catalyzed hydrolysis was inhibited by proline (66%), Zn+ (86%), Cu++ (100%), Fe (100%), PCMB (89%), and captopril (66%), but not by leucine. We also studied the transcellular transport of Phe-Pro by measuring the amount of Phe in the receiver media. In the presence of a proton gradient (AP pH6, BL pH7.4), the appearance rate of Phe in the BL media after Phe-Pro was loaded apically was at least 100 times faster than that in the AP media after Phe-Pro was loaded basolaterally. The former is also higher than the appearance rate of Phe without a transepithelial proton gradient (pH 6-pH 6) or against a proton gradient (pH7.4-pH6). The rate of appearance of Phe in the BL media (pH7.4) after Phe-Pro was loaded on the AP side (pH 6) was decreased by the presence in the AP media of proline (42%), leucine (40%), and captopril (17%), but not by Zn++. In conclusion, the transmembrane uptake of Phe-Pro is dependent on a proton gradient, and the intracellular metabolism of Phe-Pro is complete via hydrolysis by prolidase.

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Background and Purpose-Aortic stenosis, causing flow abnormalities, disturbs the normal hemodynamics in the common carotid arteries. The aim of the present study was to investigate the remodeling process of the common carotid arteries after surgical correction of aortic stenosis. Methods-Eleven subjects with aortic stenosis were studied before and 1 and 6 months after aortic valve replacement.Arterial diameter, intima-media thickness (IMT), and flow velocity were measured by echo-Doppler examination. Shear stress, blood flow, and pulsatility index were calculated. Blood viscosity and hematocrit were measured by standard methods. A control group was also enrolled. Results-Before surgery, compared with controls, patients had lower systolic peak velocity but higher mean and end-diastolic velocity. Arterial diameter, IMT, and blood flow were comparable in the 2 groups. Blood viscosity, hematocrit, wall shear stress, and pulsatility index were markedly lower in patients. After surgery, IMT was reduced (0.741Ϯ0.152 versus 0.627Ϯ0.108 mm before and 6 months after surgery, respectively; PϽ0.0001), and hematocrit and blood viscosity increased, leading to increased wall shear stress (mean wall shear stress, 7.83Ϯ1.97 versus 9.65Ϯ3.12 dyne/cm 2 before and 6 months after surgery, respectively; PϽ0.02). Conclusions-The present results demonstrate that aortic valve replacement, in subjects with aortic stenosis, leads to reduction of the common carotid artery IMT. Wall shear stress is increased after the intervention and probably mediates the remodeling process.

Our study confirms an increased prevalence of subclinical atherosclerosis in SSc patients and demonstrates a hitherto unknown association with corticosteroid cumulative dosage.

Atherosclerotic involvement of extracoronary arteries in patients undergoing myocardial revascularization can cause severe postoperative complications and increase postoperative mortality. Between January and November 1998, routine preoperative echo-Doppler study of carotid vessels, abdominal aorta and iliac-femoral arteries was performed in all patients undergoing coronary artery bypass grafting (CABG) at our institution, in order to assess the prevalence and the degree of associated vascular lesions. Correlations between echo-Doppler findings, angiographic patterns of coronary lesions and atherosclerotic risk factors were analyzed in all cases. Among 302 patients undergoing CABG, 186 (61.6%) had carotid disease, with a haemodynamically significant stenosis (>70%) of internal carotid in 31 (10.2%). Twenty-three patients had asymptomatic severe carotid disease. A significant correlation between severity of coronary disease and prevalence of severe carotid disease was found (p = 0.02). An abdominal aortic dilatation (diameter > 25 mm) was found in 20 cases (6.6%), with a diameter >35 mm in 7 patients (2.3%), 6 with triple-vessel coronary disease, and 1 with double-vessel disease. Atherosclerotic lesions of iliac-femoro-popliteal axis were found in 165 (54.6%) patients, with a strong correlation to the severity of coronary disease (p = 0.02); lesions were haemodynamically significant (> 70%) in 48 (15.8%) cases. Symptoms of carotid and peripheral vascular disease are no reliable predictors of perioperative risk in patients undergoing CABG. Non-invasive complete arterial investigation should be routinely performed in these patients, in order to plan the most suitable operative approach and to prevent perioperative vascular complications.