In the current work, we constructed two lentiviral vectors to knock down Lp-PLA2 and YKL-40 following collar-induced atherosclerosis in apoE-/- mice and elucidate whether selective or combined knockdown of the Lp-PLA2 and YKL-40 genes may ameliorate atherosclerotic plaques in apoE-/- mice. Here, APOE is linked to atherosclerosis.