Provided herein are methods of decreasing leukocyte extravasation from a lymph or blood vessel into a tissue in a mammal, methods of decreasing fluid leakage from a lymph or blood vessel in a mammal in need thereof, methods of decreasing formation of atherosclerotic plaques in a mammal in need thereof, and methods of treating atherosclerosis in a mammal that include administering to the mammal an oligonucleotide that decreases Mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4) mRNA expression in an endothelial cell. Also provided are methods of identifying a candidate agent useful for decreasing leukocyte extravasation or decreasing fluid leakage from a lymph or blood vessel in a mammal, and compositions containing an oligonucleotide that decreases Map4k4 mRNA expression in an endothelial cell and additional therapeutic agents.