Opportunistic infections in the oral cavity of the elderly may increase the incidence of systemic disease. The objective of this study was to investigate the differences in the oral bacterial flora between dependent elderly (inpatients) and independent elderly (community-dwelling residents). After multiple variables were taken into account, inpatients had significantly lower detection rates than community-dwelling residents for alpha-streptococci (p < 0.001) and Neisseria (p 0.004), and higher detection rates for Pseudomonas aeruginosa (p 0.024), methicillin-resistant Staphylococcus aureus (MRSA) (p 0.011) and Actinomyces spp. (p 0.005). Among inpatients, the requirement for a high degree of care was related negatively to detection of alpha-streptococci, but was related significantly to detection of P. aeruginosa (p 0.018) or MRSA (p 0.004). Tube-fed inpatients had a significantly lower detection rate for alpha-streptococci (p 0.041) and a higher detection rate for P. aeruginosa (p 0.004) than those who did not require tube feeding. Inpatients with a history of antibiotic use had a significantly lower detection rate for alpha-streptococci (p 0.049) and a higher detection rate for MRSA (p 0.007) than those without a history of antibiotic use. The detection rates for P. aeruginosa or MRSA in inpatients without alpha-streptococci were higher than in inpatients with alpha-streptococci after controlling for age and gender (P. aeruginosa, p 0.006; MRSA, p 0.001). Overall, detection of alpha-streptococci had an inverse correlation with the detection of P. aeruginosa and MRSA in the oral cavity and is likely to be an indicator of pathogenic bacterial infection.

Most seven transmembrane receptors (7TMRs) are G protein-coupled receptors; however, some 7TMRs evoke intracellular signals through β-arrestin as a biased receptor. As several β-arrestin-biased agonists have been reported to be cardioprotective, we examined the role of the chemokine receptor CXCR7 as a β-arrestin-biased receptor in the heart. Among 510 7TMR genes examined, Cxcr7 was the most abundantly expressed in the murine heart. Single-cell RNA-sequencing analysis revealed that Cxcr7 was abundantly expressed in cardiomyocytes and fibroblasts. Cardiomyocyte-specific Cxcr7 null mice showed more prominent cardiac dilatation and dysfunction than control mice 4 weeks after myocardial infarction. In contrast, there was no difference in cardiac phenotypes between fibroblast-specific Cxcr7-knockout mice and control mice even after myocardial infarction. TC14012, a specific agonist of CXCR7, significantly recruited β-arrestin to CXCR7 in CXCR7-expressing cells and activated extracellular signal-regulated kinase (ERK) in neonatal rat cardiomyocytes. Cxcr7 expression was significantly increased and ERK was activated in the border zone of the heart in control, but not Cxcr7 null mice. These results indicate that the abundantly expressed CXCR7 in cardiomyocytes may play a protective role in the heart as a β-arrestin-biased receptor and that CXCR7 may be a novel therapeutic target for myocardial infarction.

Oxidative stress has been implicated in cardiac remodeling (cardiac fibrosis and hypertrophy), which impairs cardiac function and metabolism; therefore, it is anticipated antioxidative compounds will have protective properties against cardiac remodeling. Luteolin (3’,4’,5,7-tetrahydroxyflavone), a widely distributed flavonoid found in many herbal extracts including celery, green pepper, perilla leaves and seeds, and chamomile, is a known to be a potent antioxidant and was previously demonstrated to exert an antifibrotic effect in the lungs and the liver. In this study, we clearly demonstrate that oral pretreatment with the higher-luteolin diet (0.035% (wt/wt)) protected against cardiac fibrosis and hypertrophy as well as a hyperoxidative state in Ang II-infused rats. In cardiac tissue, increased gene expression levels of TGFβ1, CTGF, Nox2, Nox4, ANP, and BNP induced by Ang II were restored by oral pretreatment of this high-luteolin diet. In cultured rat cardiac fibroblasts, H2O2-induced TGFβ1 expression and the phosphorylation of JNK were suppressed by luteolin pretreatment. In conclusion, food-derived luteolin has protective actions against Ang II-induced cardiac remodeling, which could be mediated through attenuation of oxidative stress.

SummaryAngiotensin II (AngII) type I receptor (AT1R) recognizes AngII, a cardiovascular peptide hormone that acts as a terminal effector of the renin-angiotensin system (RAS). AT1R belongs to the rhodopsin-like peptidergic family of G protein-coupled receptors (GPCRs) and serves as a therapeutic target for the treatment of cardiovascular diseases, such as hypertension, cardiac hypertrophy and heart failure. Classically, AT1R was considered to signal only through G proteins. However, recent studies have revealed that AT1R is capable of activating G protein-independent signaling that is mediated by β-arrestins. β-arrestin is a cytosolic scaffold that is recruited to the activated GPCRs. In vitro and ex vivo studies have demonstrated that the activation of the AT1R-β-arrestin pathway stimulates contractility and exerts prosurvival effects in cardiomyocytes. TRV027, a potent synthetic β-arrestin-biased ligand for AT1R, specifically activates AT1R-β-arrestin signaling without stimulating G proteins. In preclinical studies, TRV027 not only produced vasodilation by antagonizing the AT1R-Gαq pathway but also enhanced cardiac performance by activating AT1R-β-arrestin signaling. Because of this unique pharmacological profile, TRV027 is now being evaluated in a phase II clinical trial as a novel therapeutic for acute heart failure (AHF). (Int Heart J 2015; 56: 485-488)

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