Objective:To investigate the regulation of matrix metalloproteinases(MMPs) and tissue inhibitors of metalloproteinases(TIMPs) in human microvascular endothelium(HMEC-1) exposed to erythrocytes infected by different strains ofPlasmodium falciparum (P. falciparum).Methods:HMEC-1 cells were co-incubated for72 h with erythrocytes infected by late stage trophozoite of D10(chloroquine-sensitive) orW2(chloroquine-resistant)P. falciparum strains.Cell supatants were then collected and the levels of pro- or active gelatinasesMMP-9 andMMP-2 were evaluated by gelatin zymography and densitometry.The release of pro-MMP-9,MMP-3,MMP-1 andTIMP-1 proteins was analyzed by west blotting and densitometry.Results:Infected erythrocytes inducedde novo proMMP-9 andMMP-9 release.Neither basal levels of proMMP-2 were altered, nor activeMMP-2 was found.MMP-3 andMMP-1 secretion was significantly enhanced, whereas basalTIMP-1 was unaffected.All effects were similar for both strains. Conclusions:P. falciparum parasites, either chloroquine-sensitive or -resistant, induce the release of activeMMP-9 protein from human microvascular endothelium, by impairing balances between proMMP-9 and its inhibitor, and by enhancing the levels of its activators.This work provides new evidence onMMP involvement in malaria, pointing atMMP-9 as a possible target in adjuvant therapy.