Background: Little is known about the pathogenesis of cardiomyocyte hypertrophy caused by periodontitis pathogens. The purpose of this study was to determine the effect of the periodontal pathogen Porphyromonas gingivalis on cardiomyocyte hypertrophy.
Methods: Matrix metalloproteinase (MMP)-2 and MMP-9 activities and cellular morphology were measured by gelatin zymography and immunofluorescence after P. gingivalis-medium treatment with or without SB203580 (p38 mitogen-activated protein kinase cascade [p38] inhibitor), U0126 (mitogen-activated protein kinase kinase [MAPKK] inhibitor), LY294002 (phosphoinositide 3-kinase [PI3K] inhibitor), cyclosporin A (CsA; calcineurin inhibitor), SP600125 (c-Jun N-terminal kinase [JNK] inhibitor), proinflammatory interleukin (IL)-1, or anti-inflammatory IL-10 in cultured cardiomyoblast H9c2 cells.
Results: P. gingivalis medium increased MMP-9 activities and cellular sizes (+87%) of H9c2 cells, whereas Actinobacillus actinomycetemcomitans medium and Prevotella intermedia medium had no effects. The increased activity of MMP-9 treated with P. gingivalis medium was not mediated through p38, extracellular-regulated kinase (ERK), PI3K, calcineurin, and JNK signaling pathways and was not inhibited by IL-10. However, the hypertrophy of H9c2 cells induced with P. gingivalis medium was reduced by administration of SB203580 (-37%), U0126 (-35%), LY294002 (-49%), CsA (-49%), and SP600125 (-24%).
Conclusions: Our findings suggest that P. gingivalis medium elevated MMP-9 activity and induced cardiomyoblast hypertrophy. However, P. gingivalis-induced H9c2 cell hypertrophy was mediated through p38, ERK, PI3K, calcineurin, and JNK signaling pathways, which are in a totally different regulatory pathway from P. gingivalis-elevated MMP-9 activity. These findings provide evidence that P. gingivalis infection activated multiple factors via different pathways to induce the development of hypertrophy of H9c2 cardiomyoblast cells.