Porphyromonas gingivalis Induced Fragmentation of Type IV Collagen Through Macrophage-Activated MMP-9: (In Vitro Study of Collagenolytic Mechanism in Pathogenesis of Atherosclerotic Plaque Rupture)

Abstract

BACKGROUND: Periodontitis is caused mostly by Porphyromonas gingivalis (P.gingivalis) and it is related to acute coronary syndrome. P.gingivalis readily invades blood circulation and potentially induces collagenolytic activity of inflammatory cells that results in collagen vascular degradation leading to atherosclerotic plague rupture (APR). APR is responsible for the occurence of fatal cardiovascular events such as acute myocardial infraction (AMI).AIMS: To show that P.gingivalis potentially induces fragmentation of the type IV vascular collagen due to macrophage-activated MMP-9.MATERIAL AND METHODS: The ability of P.gingivalis to induce the type IV collagen fragmentation, shown by digesting type IV collagen with the supernatant of monocyte-derived macrophage activated by exposure to P.gingivalis suspension for 18 hours, 37oC, 5%CO2. The type IV collagen fragments were analyzed by SDS-PAGE and confirmed by Western-blotting. Antibody of type IV collagen produced and confirmed by dot-blotting prior to its being used as primary antibody of Western-blotting. The existence of MMP-9 was detected by Dot-blot and Western-blot technique, while the MMP-9 activity was assessed by SDS-PAGE and zymograms.RESULTS: Our data showed that P.gingivalis induced macrophage to produce MMP-9 as one of collagenolytic components, and interaction with P.gingivalis proteases enhanced the proteolytic activity and resulted in degradation of type IV collagen with molecular weight of 88 kDa into two smaller fragments with molecular weight of 80 kDa and 60 kDa. CONCLUSION: P.gingivalis induced macrophage to activate its MMP-9 that led to fragmentation of vascular type IV collagen in the pathogenesis of atherosclerotic plaque rupture. KEYWORDS: P.gingivalis, macrophage, type IV collagen fragmentation, atherosclerotic plaque rupture, AMI

The Roles of Periodontal Bacteria in Atherosclerosis

“…This contributed to an enlarged AS lesion area, accompanied by an escalation in macrophage content and a reduction in VSMC area, thereby fostering plaque instability [ 63 ]. Pg also triggered macrophages to secret MMP9, thereby inducing the fragmentation of vascular type IV collagen, which weakened the structural support of the plaque and worsen its destabilized [ 109 ]. Be, the heightened vascular inflammation, also impairs plaque stability [ 110 ].…”

“…Pg -induced imbalance in the differentiation of Th17 and Treg cells worsens inflammation within the plaque [ 63 ]. Increased secretion of MMP9 by macrophages promotes collagen degradation and plaque instability [ 109 ]. Pg promotes platelet aggregation and thrombus formation by interacting with IgG and Fc γRIIa receptors [ 111 ] (drawn by Figdraw).…”

Unexpected Relationships: Periodontal Diseases: Atherosclerosis–Plaque Destabilization? From the Teeth to a Coronary Event

“…In the study by Mubarokah et al, it was found that P. gingivalis induced macrophage to secrete matrix metallopeptidase 9 that led to fragmentation of vascular type IV collagen. This mechanism plays an important role in pathogenesis of atherosclerotic plaque rupture [ 86 ].…”