Introduction: Lipoprotein (a) [Lp(a)] is a peculiar lipoprotein species containing a unique glycoprotein apolipoprotein(a) [apo(a)] encoded by the LPA gene. Lp(a) is causatively, independently and significantly associated with CAD and calcified aortic valve stenosis. MiRs are approximately 22 nucleotides in length and work by inducing RNA silencing, thus reducing target genes expression. The influence of these regulatory elements on the expression of LPA remains unknown. Hypothesis: Apo(a) and Lp(a) plasma levels are genetically regulated by miRs. Method: A prediction software was used to identify miR candidates targeting the human LPA mRNA open reading frame (ORF). We investigated the selected candidates by transfecting these miRs (i) in HEK293 cells stably expressing a short LPA isoform (i.e. 17 KIV domains) and (ii) in the Hep3B human hepatoma cell line that endogenously express LPA . A validated siRNA targeting LPA and a scrambled siRNA were used as positive and negative controls, respectively. LPA expression was assessed by RT-qPCR. Apo(a) protein expression and secretion in the culture medium were assessed by Western Blot and ELISA, respectively. Results: We identified four miR candidates (miR22, miR194, miR218, and miR455) based on sequence complementarity between their seed region and the LPA mRNA ORF. Compared with the negative control, only miR455 significantly reduced LPA mRNA expression (-67±8%) as well as apo(a) intracellular abundance (-41±9%) and apo(a) secretion (-36±9%) in the culture medium ( p<0.001 , all). Similar reductions were observed with the positive siRNA control (-77±4%, -41±11%, -53±11 %, p<0.001 all, respectively). No significant effect on LPA expression was seen with the three other miR candidates. Conclusion: These in vitro results suggest that at least one human miR has the potential to regulate the circulating levels of Lp(a) in vivo . This will be verified by measuring miR455 abundance in liver and plasma samples from individuals with high vs. low Lp(a) plasma concentrations. Our study also underlines that targeting LPA with interfering RNAs is likely a regulatory process occurring in humans.