The transient receptor potential vanilloid type 1 (TRPV1) is crucial in the pathogenesis of atherosclerosis; yet its role and underlying mechanism in the formation of macrophage foam cells remain unclear. Here, we show increased TRPV1 expression in the area of foamy macrophages in atherosclerotic aortas of apolipoprotein E-deficient mice. Exposure of mouse bone-marrow-derived macrophages to oxidized low-density lipoprotein (oxLDL) upregulated the expression of TRPV1. In addition, oxLDL activated TRPV1 and elicited calcium (Ca2+) influx, which were abrogated by the pharmacological TRPV1 antagonist capsazepine. Furthermore, oxLDL-induced lipid accumulation in macrophages was ameliorated by TRPV1 agonists but exacerbated by TRPV1 antagonist. Treatment with TRPV1 agonists did not affect the internalization of oxLDL but promoted cholesterol efflux by upregulating the efflux ATP-binding cassette (ABC) transporters ABCA1 and ABCG1. Moreover, the upregulation of ABC transporters was mainly through liver X receptorα- (LXRα-) dependent regulation of transcription. Moreover, the TNF-α-induced inflammatory response was alleviated by TRPV1 agonists but aggravated by the TRPV1 antagonist and LXRαsiRNA in macrophages. Our data suggest that LXRαplays a pivotal role in TRPV1-activation-conferred protection against oxLDL-induced lipid accumulation and TNF-α-induced inflammation in macrophages.
1 January 2022 in Annals of Translational Medicine
Background: Accumulated experience and advances in device technology have led to the increasing off-label use of transcatheter aortic valve replacement (TAVR) for pure native aortic valve regurgitation (PNAR). This study aimed to evaluate the procedural and long-term outcomes of using newer-generation transcatheter heart valves (THVs) versus early-generation self-expanding CoreValve (Medtronic, Minneapolis, USA) to treat PNAR. Methods: TAVRs were performed with the use of early- (N=15) and newer-generation (N=10) THVs in a total of 25 consecutive PNAR patients at an intermediate-to-high risk for surgical aortic valve replacement [mean Society of Thoracic Surgeons (STS) score of 6.8±4.5]. Procedural and clinical outcomes were reported according to the Valve Academic Research Consortium 2 criteria. The primary end-point of the study was all-cause mortality, myocardial infarction (MI), disabling stroke, and readmission due to heart failure. Results: The device success rate of the newer-generation THVs was significantly higher than that of the early-generation CoreValve (100% vs. 33%, P<0.01), which was mainly driven by less frequent need for implanting a second THV (0% vs. 53%, P<0.01). Although the procedural success rates were 100% for both early- and newer-generation valves, the mean procedure fluoroscopic times which the newer-generation device group required, were significantly shorter (P<0.01) and the amount of contrast medium used in this group, markedly smaller (P<0.01), compared to those of the early-generation CoreValve group. During a median follow-up of 48 months, event-free survival was better in patients undergoing TAVR with the newer-generation THVs, although the differences were not statistically significant (log-rank test, P=0.137). According to multivariate analysis, a higher baseline STS score and longer intensive care unit stays are independent predictors of adverse outcomes. Conclusions: Evidently, the treatment of PNAR with TAVR using the newer-generation THVs yielded better procedural outcomes and is a valuable therapeutic option in selective patients. Keywords: Transcatheter aortic valve replacement (TAVR); pure native aortic regurgitation (AR); transcatheter heart valves (THVs); procedural and clinical outcomes
Background: Possible sarcopenia, aortic valve stenosis, and malnutrition are important issues that afflict older adults. Objective: The aims of this study were to compare the differences in nutritional status and family support in older adults with possible sarcopenia and those without sarcopenia after undergoing transcatheter aortic valve implantation (TAVI) and to identify the predictors of malnutrition and demonstrate changes in heart function over time after undergoing TAVI. Methods: A case-control design was conducted. Possible sarcopenia was identified by measuring calf circumference, grip strength, and gait speed. The Mini Nutritional Assessment-Short Form and numerical family support rating scale were used to collect data. Left ventricular ejection fraction and New York Heart Association (NYHA) functional class were assessed at 5 time points to evaluate heart function. Results: Eighty-one participants were categorized into those without sarcopenia (34) and those with possible sarcopenia (47). Logistic linear regression showed albumin and possible sarcopenia to be predictors of malnutrition (odds ratio, 5.5; 95% confidence interval, 1.02–30.19). Family support was associated with nutrition status (P = .019). For patient heart function, the results of NYHA functional class and left ventricular ejection fraction improved over time after TAVI. The improvement in NYHA functional class at T2 was significantly different between the 2 groups compared with that at T0. Conclusions: The nutrition level was higher among participants without sarcopenia than those with possible sarcopenia. Approximately 90% of the participants indicated that they had high family support. Demographic factors and albumin levels could be used to evaluate risk of malnutrition. Patients without possible sarcopenia showed greater improvement in NYHA class.
Hydrogels’ exceptional mechanical strength and skin-adhesion characteristics offer significant advantages for various applications, particularly in the fields of tissue adhesion and wearable sensors. Herein, we incorporated a combination of metal-coordination and hydrogen-bonding forces in the design of stretchable and adhesive hydrogels. We synthesized four hydrogels, namely PAID-0, PAID-1, PAID-2, and PAID-3, consisting of acrylamide (AAM), N,N′-methylene-bis-acrylamide (MBA), and methacrylic-modified dopamine (DA). The impact of different ratios of iron (III) ions to DA on each hydrogel’s performance was investigated. Our results demonstrate that the incorporation of iron–dopamine complexes significantly enhances the mechanical strength of the hydrogel. Interestingly, as the DA content increased, we observed a continuous and substantial improvement in both the stretchability and skin adhesiveness of the hydrogel. Among the hydrogels tested, PAID-3, which exhibited optimal mechanical properties, was selected for adhesion testing on various materials. Impressively, PAID-3 demonstrated excellent adhesion to diverse materials and, combined with the low cytotoxicity of PAID hydrogel, holds great promise as an innovative option for biomedical engineering applications.