Table 4.

Review of the key molecular elements and their mechanism of action used by P. gingivalis to induce foam cell formation

Authors (Year)	Key molecular element	Mechanism of Action	References
Yang et al. (2020)	LIMP2	P. gingivalis induces foam cell formation via NF-κB and JNK pathways, which enhance the expression of LIMP2, caveolin-1 (CAV-1), and their interactions.	[41]
Gupta et al. (2019)	TRPV4	TRPV4 can regulate oxLDL uptake in macrophages and this mechanosensitive channel is sensitive to the extracellular matrix stiffness induced by P. gingivalis LPS.	[44]
Kim et al. (2018)	HDL	P. gingivalis can induce HDL oxidation, which prevents its athero-protective effects and promotes athero-inductive effects by eliciting pro-inflammatory cytokines secretion.	[48]
Liang et al. (2016)	CD36, NF-κB, ERK1/2, and p65	The P. gingivalis infection can cause CD36 upregulation through the pathways mediated by NF-κB, ERK1/2, and p65.	[46]
Shaik-Dasthagirisaheb et al. (2016)	Modification of genes subsequent in macrophage-infected P. gingivalis	P. gingivalis can up-regulate and down-regulate the genes involved in lipid uptake and efflux, respectively. P. gingivalis can also enhance the expression of genes associated with inflammatory biomarkers, cell adhesion, and ECM modification.	[43]
Li et al. (2013)	P. gingivalis LPS, CD36, ABCA-1, calpain, HO-1	P. gingivalis LPS induces foam cell formation through HO-1 expression, which results in the activation of the cJun/AP-1 pathway that can promote upregulation of CD36 and downregulation of ABCA-1via upregulation of calpain activity.	[47]
Shaik-Dasthagirisaheb et al. (2013)	P. gingivalis LPS, Myeloid differentiation factor 88 (MyD88)	P. gingivalis LPS can induce foam cell formation, regardless of the presence or the absence of LDL. Moreover, the knockout of the MyD88 gene can markedly reduce foam cell formation.	[42]
Miyakawa et al. (2004)	OMV	P. gingivalis and its OMVs could induce LDL aggregation in a dose-dependent manner by proteolysis of apo B-100 protein and modification of LDL to induce higher mobility of the final LDLs.	[36]
Giacona et al. (2004)	P. gingivalis fimbria	The major fimbria of P. gingivalis plays a key role in inducing foam cell formation and P. gingivalis invasion into the macrophage cells. Moreover, the major fimbria enhances the recovery of P. gingivalis in the presence of antibiotics.	[37]
Kuramitso et al. (2003)	P. gingivalis fimbria, P. gingivalis LPS, MCP-1	The induction of MCP-1 secretion from the endothelial cells, caused by P. gingivalis, can attract more monocytes to the site and accelerate the process of foam cell formation and eventually, atherosclerosis.	[45]
Qi et al. (2003)	P. gingivalis LPS, OMV	Induction of cholesterol binding and intake by macrophages	[35]

Abbreviations: ECM: Extra-cellular matrix, HDL: High-density lipoprotein, HO-1: heme oxygenase-1, LIMP2: lysosomal integral protein 2, P. gingivalis: Porphyromonas gingivalis, OMV: Outer Membrane Vesicles, TRPV4: Transient receptor potential channel of the vanilloid subfamily 4