Abstract: | Background: Periodontitis (PD), which possesses bidirectional relationships with diabetes (Engebretson, 2013), has been reported to increase the risk of cardiovascular diseases (CVD) in systematic reviews (Bahekar, 2007). Moreover, this association between PD and CVD is independent of confounders such as diabetes, as suggested by American Heart Association (Lockhart, 2012). However, the causal link remains inconclusive (Tonetti, 2013). Objective: We sought to investigate the mechanisms underlying the correlation between PD and CVDs. Methods: Canonical pathway Analysis was conducted by comparing differentially expressed RNA-seq data using p-value and z-score visualization to identify underlying mechanisms among patients with indications of atherosclerotic CVD (ACVD) (n = 101), myocardial infarction (n = 34), ischemic stroke (n = 25), and periodontitis (n = 90). Collected samples included plaques for ACVD, peripheral blood for myocardial infarction and ischemic stroke, and periodontium for periodontitis. RNA-seq data with -log10(P) values larger than 1.3 were considered significant, and positive z-scores indicate up-regulation. Results: Among the mechanisms underlying the correlation between PD and CVD ordered based on the sum of -log10(P) values for the recruited diseases, leukocyte extravasation signaling was highly expressed in all CVD subgroups when compared to healthy donors, with -log10(P) values being 15.62 for ACVD, 14.52 for myocardial infarction, 18.63 for ischemic stroke, and 18.14 for PD; and Z scores being 3.87 for ACVD, 4.5 for myocardial infarction, 2.6 for ischemic stroke, and 3.68 for PD. Conclusion: Pathways underlying the association between PD and CVDs involved activation of leukocyte extravasation signaling. Further cohort studies are warranted. |