Correlation of contrast sensitivity with ganglion cell/inner plexiform layer thickness and damage location in glaucoma with varying severity.

OBJECTIVES: To investigate the correlation of contrast sensitivity with macular region ganglion cell/inner plexiform layer (GC/IPL) thickness and damage location in open-angle glaucoma (OAG) of varying severity. METHODS: Cross-sectional study with 106 patients (203 eyes) who had OAG. Contrast sensitivity of each eye evaluated by quick contrast sensitivity function test based on intelligent algorithm. The GC/IPL thickness measured with optical coherence tomography; six sectors were delineated for localization of damage area. All eyes were grouped by the healthy macular sector and divided into pre-perimetric, early, moderate, and advanced stages, according to severity of visual field impairment. RESULTS: Mean GC/IPL thickness in the entire macular region and each sector were correlated with parameters that reflected contrast sensitivity (p < 0.01). The structure-function correlations were stronger nasally compared with temporally, and superiorly compared with inferiorly. Eyes with normal structure in inferior temporal sector had less visual field (p' = 0.024) and macular damage (p' = 0.034) compared with eyes that had healthy superior nasal sector; there was no difference in contrast sensitivity (p = 0.898). The structure-function correlations were significant in early, moderate, and advanced glaucoma (p < 0.05) but not in pre-perimetric glaucoma (p = 0.116). CONCLUSIONS: GC/IPL thinning in all sectors of the macular region in OAG was correlated with contrast sensitivity impairment, whereas the inferior temporal sector was least affected. Contrast sensitivity was supported as a severity evaluation indicator of early, moderate, and advanced glaucoma, but not of pre-perimetric glaucoma.

Association between contrast sensitivity function and structural damage in primary open-angle glaucoma.

AIMS: To evaluate the association between contrast sensitivity function (CSF) and glaucomatous structural damage in primary open-angle glaucoma (POAG). METHODS: A cross-sectional study was performed with 103 patients (103 eyes) aged 25-50 years who had POAG without any other ocular disease. CSF measurements were obtained by the quick CSF method, a novel active learning algorithm that covers 19 spatial frequencies and 128 contrast levels. The peripapillary retinal nerve fibre layer (pRNFL), macular ganglion cell complex (mGCC), radial peripapillary capillary (RPC) and macular vasculature were measured by optical coherence tomography and angiography. Correlation and regression analyses were used to assess the association of area under log CSF (AULCSF), CSF acuity and contrast sensitivities at multiple spatial frequencies with structural parameters. RESULTS: AULCSF and CSF acuity were positively associated with pRNFL thickness, RPC density, mGCC thickness and superficial macular vessel density (p<0.05). Those parameters were also significantly associated with contrast sensitivity at 1, 1.5, 3, 6, 12, 18 cycles per degree spatial frequencies (p<0.05) and, the lower the spatial frequency, the higher the correlation coefficient. RPC density (p=0.035, p=0.023) and mGCC thickness (p=0.002, p=0.011) had significant predictive value for contrast sensitivity at 1 and 1.5 cycles per degree, with adjusted R 2 of 0.346 and 0.343, respectively. CONCLUSIONS: Full spatial frequency contrast sensitivity impairment, most notably at low spatial frequencies, is a characteristic change in POAG. Contrast sensitivity is a potential functional endpoint for the measurement of glaucoma severity.

P66Shc is increased in peripheral blood mononuclear cells of the patients with obstructive sleep apnea.

Objective: Obstructive sleep apnea (OSA) is characterized by nocturnal intermittent hypoxemia and linked to oxidative stress. Evidence demonstrated that p66Shc plays a key role in regulating oxidative stress. This study aimed to investigate the expression of p66Shc in peripheral blood mononuclear cells (PBMCs) of patients with OSA and the association with polysomnographic parameters. Methods: Fifty-four OSA subjects and 19 no OSA controls were enrolled in this study. All the subjects underwent standard polysomnography. P66Shc mRNA and protein levels in the PBMCs were detected by quantitative real-time polymerase chain reaction and western blotting. Plasma 3-nitrotyrosine (3-NT), oxidized low density lipoprotein (oxLDL), and advanced oxidation protein products (AOPP) were measured by ELISA method. Results: P66Shc mRNA and protein levels in PBMCs were significantly higher in OSA patients than in controls. P66Shc mRNA was positively correlated with plasma 3-NT, oxLDL, AOPP, hypopnea index (AHI), oxygen desaturation index (ODI), percentage of total sleep time with oxygen saturation (SaO2) below 90% (CT90), epworth sleepiness scale (ESS) and lymphocytes; negatively correlated with lowest SaO2 (LSaO2) and mean SaO2 (MSaO2). Further multivariate linear regression analysis showed that p66Shc mRNA levels were independently associated with AHI, MSaO2 and CT90. Conclusions: Oxidative stress regulator p66Shc may play a role in the pathophysiology of OSA and might serve as a potential biomarker for this disease.

Characteristics of the fecal microbiome and metabolome in older patients with heart failure and sarcopenia.

Background: Increasing evidence supports that gut microbiota plays an important role in the development of cardiovascular diseases. The prevalence of sarcopenia is increasing in patients with heart failure. Muscle wasting is an independent predictor of death in heart failure patients. Aims: In this study, we aimed to explore the characteristics of gut microbiota and metabolites in heart failure patients with or without sarcopenia. Methods: Fecal samples of 33 heart failure patients without sarcopenia, 29 heart failure patients with sarcopenia, and 15 controls were collected. The intestinal microbiota was analyzed using 16S rRNA sequencing and the metabolites were detected using the gas chromatography-mass spectrometry method. Results: There were significant differences in the overall microbial community structure and diversity between control and heart failure patients with or without sarcopenia. However, no clear clustering of samples was observed in heart failure with and without sarcopenia patients. Several bacterial, particularly Nocardiaceae, Pseudonocardiaceae, Alphaproteobacteria, and Slackia were significantly enriched in the heart failure patients without sarcopenia, while Synergistetes was more abundant in the heart failure patients with sarcopenia. Isobutyric acid, isovaleric acid, and valeric acid were lower in heart failure patients with sarcopenia than that without sarcopenia but lacked significance. Conclusions: This study demonstrates that there are differences in the gut microbiota between control individuals and heart failure patients with or without sarcopenia. Modulating the gut microbiota may be a new target for the prevention and treatment of sarcopenia in heart failure patients.

Aspirin alleviates pulmonary fibrosis through PI3K/AKT/mTOR-mediated autophagy pathway.

Idiopathic pulmonary fibrosis (IPF) is a chronic and irreversible lung disease with limited therapeutic options. Aspirin can alleviate liver, kidney, and cardiac fibrosis. However, its role in lung fibrosis is unclear. This study aims to investigate the effects of aspirin on lung fibroblast differentiation and pulmonary fibrosis. TGF-ß1-induced human embryonic lung fibroblasts, IPF lung fibroblasts, and bleomycin-induced lung fibrosis mouse model were used in this study. The results showed that aspirin significantly decreased the expression of Collagen 1A1, Fibronectin, Alpha-smooth muscle actin, and equestosome1, and increased the ratio of light chain 3 beta II/I and the number of autophagosome in vivo and in vitro; reduced bleomycin-induced lung fibrosis. Aspirin also decreased the ratios of phosphorylated phosphatidylinositol 3 kinase (p-PI3K)/PI3K, protein kinase B (p-AKT)/AKT, and mechanistic target of rapamycin (p-mTOR)/mTOR in vitro. Autophagy inhibitor 3-methyladenine, bafilomycin-A1, and AKT activator SC-79 abrogated the effects of aspirin. These findings indicate that aspirin ameliorates pulmonary fibrosis through a PI3K/AKT/mTOR-dependent autophagy pathway.

Obstructive Sleep Apnea Impacts Cardiac Function in Dilated Cardiomyopathy Patients Through Circulating Exosomes.

Background: Obstructive sleep apnea (OSA) is common and independently associated with heart failure. This study aimed to investigate the impact of OSA on heart function in patients with dilated cardiomyopathy (DCM) as well as the possible mechanism related to exosomes regulated autophagy. Methods and Results: A total of 126 patients with DCM who underwent sleep evaluations were analyzed retrospectively. Cardiomyocytes were treated with exosomes isolated from untreated OSA patients and healthy controls. Fibrotic and hypertrophic markers were evaluated, and Akt/mTOR pathway-mediated autophagy was investigated. DCM patients with severe OSA had larger right ventricular end-diastolic diameter (RVEDd) and right atrial diameter (RAD) and increased N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels than DCM patients without OSA. Moreover, NT-proBNP and diabetes mellitus were independently correlated with the apnea-hypopnea index in multiple linear regression analysis. Treatment with OSA-derived exosomes significantly increased Col1A1, ANP, and BNP protein expression and decreased the expression of the autophagy markers LC3B II/I and beclin1. Rapamycin treatment significantly increased the decreased autophagy markers and attenuated the increased expression of Col1A1, ANP and BNP induced by OSA-derived exosomes. Conclusion: The severity of OSA is significantly associated with cardiac injury and remodeling. The underlying mechanism may be related to changed autophagy levels, which are regulated by circulating exosomes via the Akt/mTOR signaling pathway. This study may provide a new clue for the treatment of heart failure with OSA.

HDAC inhibitors as antifibrotic drugs in cardiac and pulmonary fibrosis.

Fibrosis usually results from dysregulated wound repair and is characterized by excessive scar tissue. It is a complex process with unclear mechanisms. Accumulating evidence indicates that epigenetic alterations, including histone acetylation, play a pivotal role in this process. Histone acetylation is governed by histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDACs are enzymes that remove the acetyl groups from both histone and nonhistone proteins. Aberrant HDAC activities are observed in fibrotic diseases, including cardiac and pulmonary fibrosis. HDAC inhibitors (HDACIs) are molecules that block HDAC functions. HDACIs have been studied extensively in a variety of tumors. Currently, there are four HDACIs approved by the US Food and Drug Administration for cancer treatment yet none for fibrotic diseases. Emerging evidence from in vitro and in vivo preclinical studies has presented beneficial effects of HDACIs in preventing or reversing fibrogenesis. In this review, we summarize the latest findings of the roles of HDACs in the pathogenesis of cardiac and pulmonary fibrosis and highlight the potential applications of HDACIs in these two fibrotic diseases.

Interaction between gut microbiome and cardiovascular disease.

Traditional cardiovascular risk factors do not underlie all incidence of cardiovascular disease. In recent years, accumulating evidence has demonstrated that gut microbiota and its metabolites also play a pivotal role in the onset and development of cardiovascular disease, including atherosclerosis, hypertension, heart failure, atrial fibrillation and myocardial fibrosis. Trillions of bacteria indwell the gastrointestinal tract and metabolize nutrients into trimethylamine-N-oxide, short-chain fatty acids and so on. Targeting these microorganisms and relevant metabolic pathways has beneficial effects in cardiovascular disease. This review will summarize the role of gut microbiota and its metabolites, mainly trimethylamine-N-oxide, in the pathogenesis of cardiovascular diseases, and discuss the possible mechanisms that drive cardiovascular diseases and highlight potential therapies in this field.