# Oral Microbiome and Host Health: Review on Current Advances in Genome-Wide Analysis
## 9 Oral Disease and Systemic Disease
### Non-Communicable Diseases
#### 9.1.1 Cardiovascular Disease  
CVD is a general term for atherosclerotic diseases, and atherosclerotic CVD is one of the leading causes of death in the world [100]. Generally, circulating leukocytes in the blood vessels do not adhere to the endothelium under normal conditions. However, when an inflammatory response occurs, various adhesion molecules, such as vascular cell adhesion molecule \(1\) (VCAM-1), intercellular adhesion molecule \(1\) (ICAM-1), and P-selectin, are expressed in the endothelial cells, inducing the adhesion of leukocytes [101]. When leukocytes adhere to the endothelium, they migrate into the intima, and diapedesis occurs via the expression of matrix metalloproteinases [102]. Several studies regarding the link between periodontitis and CVD have reported their positive association [100; 105; 106]. Several risk factors including smoking, diabetes, hypertension, and hypercholesterolemia have been focused on as the contributory factors in atherosclerosis; however, recent studies have suggested that immune and inflammatory mechanisms caused by oral bacteria could be an important factor in atherosclerosis [103; 104]. Oral bacteria, such as periodontal and carigenic pathogens, are known as etiological factors in the development of atherosclerosis, which is the first step of CVD. To investigate the association between oral microbiomes and atherosclerosis, several studies have been performed examining atheromatous lesions with various molecular biologic techniques. Fundamentally, periodontal pathogens were cultured in atheromatous plaque [105], and fluorescence in situ hybridization [106], DNA-DNA hybridization [107], and real-time PCR [108] results showed the presence of oral pathogens in atheromatous lesions. Based on these results, oral microbiome studies have been widely conducted on oral bacteria-induced atherosclerotic CVD (Table 2).  
\begin{table}
\begin{tabular}{p{128.0 pt} p{128.0 pt} p{128.0 pt}} \hline
**Mechanism** & **Organism** & **Result** & **Reference** \\ \hline \hline \multirow{8}{*}{Endothelial cell invasion} & & Infection of human aortic endothelial cells with invasive P. g. strain 381 resulted in the upregulation of 68 genes that code for the pro-inflammatory cytokines, adhesion molecules, and chemokines. In addition, P. g. induces procoagulant effects including enhanced tissue factor expression and activity, and suppression of tissue factor pathway inhibitors & [109] \\ \cline{2-3}  & & Co-infection with F. n. resulted in a 2–20-fold increase in the invasion of endothelial cells by P. g. strains & [110] \\ \hline \hline \multirow{8}{*}{Endothelial cell activation} & & A.a. infection in apolipoprotein E-deficient mice increased expressions of ICAM-1, E-selectin, P-selectin, MCP-1, chemokine (C-C motif) ligand 19 (CCL19), CCL21, and CCR7 in the aorta & [111] \\ \cline{2-3}  & & Coculture of endothelial cells with P.g. increased ICAM-1, VCAM-1 and P-and E-selectins & [112; 113] \\ \cline{2-3}  & & P.g. & P.g. cleaves apoB-100 and increases the expression of apoM in LDL in whole blood & [114] \\ \cline{2-3}  & & A.a. induces MMP-9 expression and proatherogenic lipoprotein profile in apoE-deficient mice & [115] \\ \cline{2-3}  & & & \\ \cline{2-3}  & & & \\ \end{tabular}
\end{table}
Table 2: Oral Microbiome Related to CVD.