Exploration of available transcriptomic datasets revealed crosstalk genes (e.g., RASGRP2, VAMP7, SNX3, HMGB1, SUMO1, FIBP, PSMB2, SELPLG, and SEC61G) and significant pathways (bacterial invasion of epithelial cells, platelet activation, and VEGF signaling pathway) as the top candidate molecular linkage mechanisms between atherosclerosis and periodontitis. The gene discussed is HMGB1; the disease is periodontitis.