to the regulatory role of LPP3 in vascular and embryonic development, inactivation of this protein can contribute to cardiovascular disease and developmental complications. For example, inducible inactivation of LPP3 in both endothelial and hematopoietic cells leads to atherosclerosis due to accumulation of LPA in human plaques. Likewise, plasma LPA levels are significantly elevated in patients with acute coronary syndromes. It was further observed that reduced levels of endothelial LPP3 is associated with disturbed flow and mechano-regulation in blood vessels. During embryonic development in mice, inactivation of LPP3 results in early lethality in part due to failure of extra-embryonic vascular development. Abnormal activation of LPA signaling has also been implicated in cancer, fibrotic disorders, and metabolic syndrome (involving insulin resistance). Clinical Marker In humans, PPAP2B emerged as 1 of 13 new loci associated with coronary artery disease by genome-wide association studies (GWAS). This prediction appears to be independent of traditional risk factors for cardiovascular disease such as high cholesterol levels, high blood pressure, obesity, smoking, and diabetes mellitus. Additionally, a multi-locus genetic risk score study, based on a combination of 27 loci including the PPAP2B gene, identified individuals at increased risk for both incident and recurrent coronary artery disease events, as well as an enhanced clinical benefit from statin therapy. The study was based on a community cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE IT-TIMI 22). Taken together, these findings also suggest that PPAP2B and LPA may serve a role in predicting and screening coronary artery disease for early prevention. Interactions Interactive Pathway Map LPP3 participates in interactions within the triacylglyceride synthesis and sphingolipid metabolism pathways. References Further reading