While several previous studies have indicated the link between periodontal disease (PD) and myocardial infarction (MI), theunderlying mechanisms remain unclear. Autophagy, a cellular quality control process that is ac...While several previous studies have indicated the link between periodontal disease (PD) and myocardial infarction (MI), theunderlying mechanisms remain unclear. Autophagy, a cellular quality control process that is activated in several diseases, includingheart failure, can be suppressed by Porphyromonas gingivalis (P.g.). However, it is uncertain whether autophagy impairment byperiodontal pathogens stimulates the development of cardiac dysfunction after MI. Thus, this study aimed to investigate therelationship between PD and the development of MI while focusing on the role of autophagy. Neonatal rat cardiomyocytes(NRCMs) and MI model mice were inoculated with wild-type P.g. or gingipain-deficient P.g. to assess the effect of autophagyinhibition by P.g. Wild-type P.g.-inoculated NRCMs had lower cell viability than those inoculated with gingipain-deficient P.g. Thisstudy also revealed that gingipains can cleave vesicle-associated membrane protein 8 (VAMP8), a protein involved in lysosomalsensitive factor attachment protein receptors (SNAREs), at the 47th lysine residue, thereby inhibiting autophagy. Wild-type P.g.-inoculated MI model mice were more susceptible to cardiac rupture, with lower survival rates and autophagy activity thangingipain-deficient P.g.-inoculated MI model mice. After inoculating genetically modified MI model mice (VAMP8-K47A) with wildtype P.g., they exhibited significantly increased autophagy activation compared with the MI model mice inoculated with wild-typeP.g., which suppressed cardiac rupture and enhanced overall survival rates. These findings suggest that gingipains, which arevirulence factors of P.g., impair the infarcted myocardium by cleaving VAMP8 and disrupting autophagy. This study confirms thestrong association between PD and MI and provides new insights into the potential role of autophagy in this relationship.展开更多
BACKGROUND Low-molecular-weight dextran(LMWD)is considered a safe alternative to contrast media for blood displacement during optical coherence tomography(OCT)imaging.AIM To investigate whether the use of LMWD for OCT...BACKGROUND Low-molecular-weight dextran(LMWD)is considered a safe alternative to contrast media for blood displacement during optical coherence tomography(OCT)imaging.AIM To investigate whether the use of LMWD for OCT is protective against kidney injury in patients with advanced renal insufficiency.METHODS In this retrospective cohort study,we identified 421 patients with advanced renal insufficiency(estimated glomerular filtration rate<45 mL/min/1.73 m2)who underwent coronary angiography or percutaneous coronary intervention;79 patients who used additional LMWD for OCT imaging(LMWD group)and 342 patients who used contrast medium exclusively(control group).We evaluated the differences between these two groups and performed a propensity score-matched subgroup comparison.RESULTS The median total volume of contrast medium was 133.0 mL in the control group vs 140.0 mL in the LMWD group.Although baseline renal function was not statistically different between these two groups,the LMWD group demonstrated a strong trend toward the progression of renal insufficiency as indicated by the greater change in serum creatinine level during the 1-year follow-up compared with the control group.Patients in the LMWD group experienced worsening renal function more frequently than patients in the control group.Propensity score matching adjusted for total contrast media volume consistently indicated a trend toward worsening renal function in the LMWD group at the 1-year follow-up.Delta serum creatinine at 1-year follow-up was significantly greater in the LMWD group than that in the control group[0.06(-0.06,0.29)vs-0.04(-0.23,0.08)mg/dL,P=0.001],despite using similar contrast volume.CONCLUSION OCT using LMWD may not be protective against worsening renal function in patients with advanced renal insufficiency.展开更多
基金supported by Japan Society for the Promotion of Science (JSPS) KAKENHI Grant-in-Aid for Scientific Research (C) 20K08399 (to Yasuhiro Maejima)KAKENHI 19K18985,Grant-in-Aid for JSPS Fellows+1 种基金MSD Life Science FoundationPublic Interest Incorporated Foundation (to Yuka Shiheido-Watanabe)
文摘While several previous studies have indicated the link between periodontal disease (PD) and myocardial infarction (MI), theunderlying mechanisms remain unclear. Autophagy, a cellular quality control process that is activated in several diseases, includingheart failure, can be suppressed by Porphyromonas gingivalis (P.g.). However, it is uncertain whether autophagy impairment byperiodontal pathogens stimulates the development of cardiac dysfunction after MI. Thus, this study aimed to investigate therelationship between PD and the development of MI while focusing on the role of autophagy. Neonatal rat cardiomyocytes(NRCMs) and MI model mice were inoculated with wild-type P.g. or gingipain-deficient P.g. to assess the effect of autophagyinhibition by P.g. Wild-type P.g.-inoculated NRCMs had lower cell viability than those inoculated with gingipain-deficient P.g. Thisstudy also revealed that gingipains can cleave vesicle-associated membrane protein 8 (VAMP8), a protein involved in lysosomalsensitive factor attachment protein receptors (SNAREs), at the 47th lysine residue, thereby inhibiting autophagy. Wild-type P.g.-inoculated MI model mice were more susceptible to cardiac rupture, with lower survival rates and autophagy activity thangingipain-deficient P.g.-inoculated MI model mice. After inoculating genetically modified MI model mice (VAMP8-K47A) with wildtype P.g., they exhibited significantly increased autophagy activation compared with the MI model mice inoculated with wild-typeP.g., which suppressed cardiac rupture and enhanced overall survival rates. These findings suggest that gingipains, which arevirulence factors of P.g., impair the infarcted myocardium by cleaving VAMP8 and disrupting autophagy. This study confirms thestrong association between PD and MI and provides new insights into the potential role of autophagy in this relationship.
文摘BACKGROUND Low-molecular-weight dextran(LMWD)is considered a safe alternative to contrast media for blood displacement during optical coherence tomography(OCT)imaging.AIM To investigate whether the use of LMWD for OCT is protective against kidney injury in patients with advanced renal insufficiency.METHODS In this retrospective cohort study,we identified 421 patients with advanced renal insufficiency(estimated glomerular filtration rate<45 mL/min/1.73 m2)who underwent coronary angiography or percutaneous coronary intervention;79 patients who used additional LMWD for OCT imaging(LMWD group)and 342 patients who used contrast medium exclusively(control group).We evaluated the differences between these two groups and performed a propensity score-matched subgroup comparison.RESULTS The median total volume of contrast medium was 133.0 mL in the control group vs 140.0 mL in the LMWD group.Although baseline renal function was not statistically different between these two groups,the LMWD group demonstrated a strong trend toward the progression of renal insufficiency as indicated by the greater change in serum creatinine level during the 1-year follow-up compared with the control group.Patients in the LMWD group experienced worsening renal function more frequently than patients in the control group.Propensity score matching adjusted for total contrast media volume consistently indicated a trend toward worsening renal function in the LMWD group at the 1-year follow-up.Delta serum creatinine at 1-year follow-up was significantly greater in the LMWD group than that in the control group[0.06(-0.06,0.29)vs-0.04(-0.23,0.08)mg/dL,P=0.001],despite using similar contrast volume.CONCLUSION OCT using LMWD may not be protective against worsening renal function in patients with advanced renal insufficiency.