Dou-dou Hu1, Sohail Habib2, Xin-min Li3, Tai-ling Wang4, Bao-en Wang5, Xin-yan Zhao6. 1. Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, P.R. China. hudoudou1984@163.com. 2. International School, Capital Medical University, Beijing, P.R. China. sohail.habib@me.com. 3. Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, P.R. China. xinmin1105@gmail.com. 4. Department of Pathology, China-Japan Friendship Hospital, Beijing, P.R. China. Wang_tailing@126.com. 5. Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, P.R. China. wangbbee@126.com. 6. Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, P.R. China. Zhao_xinyan@ccmu.edu.cn.
Abstract
AIM: Angiogenesis is considered an important pathophysiological feature of portal hypertension. We investigated the ability of angiogenesis, as CD34-positive microvessel density (MVD), to differentiate portal pressure in a CCl4-induced rat cirrhosis model. METHODS: Cirrhosis was induced by intraperitoneal injection of carbon tetrachloride in 46 male adult Sprague-Dawley rats. A catheter connected to a highly sensitive pressure transducer was inserted into the portal vein to continuously record portal pressure. Fibrosis area, nodule size and MVD were assessed by image morphometry. RESULTS: Of 42 rats in which portal pressure was measured successfully, 27 (64%) had portal pressure ≥10 mmHg, defined as significant portal hypertension. MVD was 4.5-fold higher and fibrosis area 13.0-fold higher in rats with significant portal hypertension than in rats with portal pressure <10 mmHg. Portal pressure was significantly correlated with MVD (r=0.491, p<0.001) and fibrosis area (r=0.545, p<0.001) in all animals, but only MVD correlated with portal pressure (r=0.731 p<0.001) in rats with significant portal hypertension. The area under receiver operating characteristic curve for MVD in all rats was 0.953 (95% CI: 0.875-1.031) and optimum cutoff for MVD was 18/mm², with 96.3% sensitivity and 93.3% specificity. CONCLUSIONS: We found that MVD, measured by CD34 immunostaining, was better able than the fibrosis area to discriminate significant portal hypertension in rats, suggesting that MVD could be a surrogate marker for portal hypertension in patients with liver diseases.
AIM: Angiogenesis is considered an important pathophysiological feature of portal hypertension. We investigated the ability of angiogenesis, as CD34-positive microvessel density (MVD), to differentiate portal pressure in a CCl4-induced ratcirrhosis model. METHODS:Cirrhosis was induced by intraperitoneal injection of carbon tetrachloride in 46 male adult Sprague-Dawley rats. A catheter connected to a highly sensitive pressure transducer was inserted into the portal vein to continuously record portal pressure. Fibrosis area, nodule size and MVD were assessed by image morphometry. RESULTS: Of 42 rats in which portal pressure was measured successfully, 27 (64%) had portal pressure ≥10 mmHg, defined as significant portal hypertension. MVD was 4.5-fold higher and fibrosis area 13.0-fold higher in rats with significant portal hypertension than in rats with portal pressure <10 mmHg. Portal pressure was significantly correlated with MVD (r=0.491, p<0.001) and fibrosis area (r=0.545, p<0.001) in all animals, but only MVD correlated with portal pressure (r=0.731 p<0.001) in rats with significant portal hypertension. The area under receiver operating characteristic curve for MVD in all rats was 0.953 (95% CI: 0.875-1.031) and optimum cutoff for MVD was 18/mm², with 96.3% sensitivity and 93.3% specificity. CONCLUSIONS: We found that MVD, measured by CD34 immunostaining, was better able than the fibrosis area to discriminate significant portal hypertension in rats, suggesting that MVD could be a surrogate marker for portal hypertension in patients with liver diseases.