RESUMEN
Emerging evidence suggests that immune receptors may participate in many aging-related processes such as energy metabolism, inflammation, and cognitive decline. CD300f, a TREM2-like lipid-sensing immune receptor, is an exceptional receptor as it integrates activating and inhibitory cell-signaling pathways that modulate inflammation, efferocytosis, and microglial metabolic fitness. We hypothesize that CD300f can regulate systemic aging-related processes and ultimately healthy lifespan. We closely followed several cohorts of two strains of CD300f-/- and WT mice of both sexes for 30 months and observed an important reduction in lifespan and healthspan in knockout mice. This was associated with systemic inflammaging, increased cognitive decline, reduced brain glucose uptake observed by 18FDG PET scans, enrichment in microglial aging/neurodegeneration phenotypes, proteostasis alterations, senescence, increased frailty, and sex-dependent systemic metabolic changes. Moreover, the absence of CD300f altered macrophage immunometabolic phenotype. Taken together, we provide strong evidence suggesting that myeloid cell CD300f immune receptor contributes to healthy aging.
Asunto(s)
Disfunción Cognitiva , Envejecimiento Saludable , Masculino , Femenino , Ratones , Animales , Macrófagos/metabolismo , Inflamación/metabolismo , Microglía/metabolismo , Ratones Noqueados , Disfunción Cognitiva/metabolismoRESUMEN
BACKGROUND AND OBJECTIVES: The state of the coronary microcirculation is an important determinant of the myocardial viability and clinical outcomes for patients suffering with acute myocardial infarction (AMI). However, there are scant comparative studies on the most reliable invasive, on-site measurement for assessing the microvascular integrity and myocardial viability in AMI patients. The aim of this study is to evaluate the usefulness of a novel index of microcirculatory resistance (IMR) and the coronary physiologic parameters for predicting the myocardial viability after primary percutaneous coronary intervention (PCI) in AMI patients. SUBJECTS AND METHODS: Twenty-four patients (21 males, mean age: 55+/-11 years) underwent primary PCI for AMI (LAD: 17, RCA: 6, LCX: 1) were enrolled. After successful PCI, using a pressure-temperature sensor-tipped coronary wire, the thermodilution-derived CFR (CFRthermo) and coronary wedge pressure (Pcw) were measured and the ratio of the Pcw and the mean aortic pressure (Pcw/Pa) was calculated, along with the IMR, which was defined as the distal coronary pressure divided by the inverse of the hyperemic mean transit time. 18F-fluorodeoxyglucose (FDG) PET was performed after primary PCI at 7 days post-AMI to evaluate the myocardial viability by the regional percentage of FDG uptake in the infarct-related segments. RESULTS: There were good correlations between all the coronary pressure measurements and the regional FDG uptake (CFRthermo, r=0.454, p=0.026; Pcw, r=-0.407, p=0.048; Pcw/Pa, r=-0.480, p=0.018; IMR, r=-0.696, p<0.001, respectively). Multiple logistic regression analysis demonstrated that the IMR was an adjusted predictor for myocardial viability as defined by the 50% FDG-PET threshold value among all the coronary pressure measurements (OR=0.884, p=0.021). The cut-off value of IMR for predicting myocardial viability was 22 U (a sensitivity of 82%, a specificity of 85% and an accuracy of 85%). CONCLUSIONS: Intracoronary pressure wire-based indexes are useful for on-site assessment of myocardial viability after primary PCI. IMR is a novel index that represents the microvascular integrity, and it is a better predictor of myocardial damage than the current techniques for evaluating the microvasculature after primary PCI.