Coronary ischemia/reperfusion increases proliferating cell nuclear antigen in vascular endothelial cells in rat hearts

To elucidate the sequence of early events in the increase in capillarity caused by reperfusion following transient coronary occlusion, the time course of expression of proliferating cell nuclear antigen (PCNA) was studied immunohistochemically in rat hearts subjected to different periods of reperfusion after a 3 minute occlusion. Twenty-one male Wistar rats were killed after different periods of reperfusion following occlusion of the coronary artery for 3 minutes. The left ventricles were removed and paired serial sections were treated immunohistochemically for PCNA or stained to show the enzymes characteristic of the arteriolar, intermediate and venular portions of the capillary bed. The time course of PCNA expression, and its distribution in relation to the different portions, was examined. An increase in PCNA-expressing nuclei was found at 24 hours after the start of reperfusion; numbers reached a maximum between 72 and 96 hours, and at 168 hours had decreased again. The majority of PCNA-expressing elements were localized to the dipeptidylpeptidase IV-reactive (i.e. venular) capillary portions, with some in the intermediate and alkaline phosphatase-reactive (i.e. arteriolar) portions. The distribution of PCNA in the early reperfusion period suggests that angiogenesis after transient ischemia occurs mainly from the venular side of the capillary bed, with some contribution from intermediate and arteriolar capillary portions.