LMCD1 Acts As a Coactivator for E2F1 in CDC6 Expression to Promote Human Aortic Smooth Muscle Cell Replication and Atherogenesis

In exploring the mechanisms underlying restenosis, we have identified LMCD1 as a highly responsive gene to thrombin in human aortic smooth muscle cells (HASMCs). Depletion of LMCD1 levels inhibited human but not murine vascular smooth muscle cell replication. LMCD1 via interacting with E2F1 mediates thrombin‐induced CDC6 expression in the regulation of HASMC replication. Thrombin‐induced LMCD1 and CDC6 expression exhibited a requirement for PAR1‐mediated Gαq/11‐dependent PLCβ3 activation. In addition, the expression of LMCD1 was highly induced in SMC of human atherosclerotic lesions and correlated with CDC6 expression and replication marker Ki67. Furthermore, the LMCD1 and SMCαactin‐positive cells were found to possess higher cholesterol levels in the atherosclerotic lesions. Thus, these findings for the first time show that LMCD1 via acting as a coactivator for E2F1 in CDC6 expression modulates HASMC replication and hence promotes human atherogenesis.Support or Funding InformationThis work was supported by grants HL069908 and HL103575 (to GNR) and HL098435 and HL133497 (to AWO) from NHLBI of NIH.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.