Development Of Cardiovascular Disease Research Articles

PHYSICAL SYMPTOMS REACTIVITY TO DAILY STRESSORS AND CARDIOVASCULAR DISEASE: A COMPARISON OF BLACK AND WHITE ADULTS

Abstract Black adults have higher risk for cardiovascular disease (CVD) compared to their White counterparts. Biopsychosocial frameworks suggest that this racial difference may not only be due to higher stressor exposure (e.g., discrimination) but also to stressor reactivity (i.e., heightened automatic reactions to stressors). This study examined if racial disparities in CVD is explained by elevated physical symptoms in response to daily stressors (“physical symptom reactivity to stressors”). Data came from 1,727 adults (non-Hispanic Black=38%, non-Hispanic White=62%) who participated in the Midlife in the United States Study at Time-1 (T1: 2004-2009). A subset (n=1,482) was reassessed at Time-2 (T2: 2013-2019). Race, daily physical symptoms, and daily stressors were measured at T1. Physical symptom reactivity to stressors (i.e., individual slope of physical symptoms as a function of daily stressor severity) was calculated using 8-day diary data. Physician-diagnosed CVD was captured at T1 and T2. Indirect pathways (A path: race->stressor physical reactivity, B path: race->CVD) were tested, adjusting for health and sociodemographic covariates. At T1, Black adults exhibited a higher risk of CVD compared to White individuals through higher physical symptom reactivity to stressors (A path: B=0.004, SE=0.0006, p<.001; B path: B=-3.56, SE=1.32, p=.007; indirect effect=0.12, SE=0.03, 95% CI=[0.06, 0.18]). These indirect pathways were also supported when predicting the risk of CVD at T2 after controlling for T1 CVD (B path: B=-3.23, SE=1.56, p=.038; indirect effect=0.07, SE=0.04, 95% CI=[0.02, 0.16]). Findings newly suggest that racial differences in physical manifestations of stress may contribute to disproportionate development of CVD, the deadliest disease in America.

Metabesity: pathogenetic bases and predictive capabilities. A review

One of the most pressing problems of our time is obesity, recognized by the WHO as a pandemic of the XXI century. It is important to remember that obesity is a full-fledged nosological entity, but many women think that obesity is just a problem of beauty and aesthetics. It is important to note that this nosology has a number of serious consequences, starting with the development of cardiovascular disease and ending with cancer. However, the “problem in the problem” is the so-called “metabesity” – a new term that reflects a number of diseases, the pathogenesis of which is based on the metabolic syndrome. Obesity, metabolic syndrome and metabesity seem to be different concepts, but the absolute identity of the pathogenetic basis characterizes them as successive stages of one global process. In this regard, it is necessary to highlight the key mechanisms of the development of the described disorders and to consider the concept of clinical management of patients in this cohort.

The influences of smoking on the formation of Atherosclerosis

Smoking is closely related to the occurrence and development of many other cardio cerebral Vascular diseases. Smoking can increase the risk of moderate diseases such as hypertension, coronary heart disease, myocardial infarction, and stroke. Smoking will cause Vasoconstriction, increase the load of the heart, lead to poor blood circulation, and then lead to the occurrence of cardio cerebral Vascular disease. In addition, smoking can also have adverse effects on the human immune system. Smoking can lead to a decrease in immune function and increase the risk of infections. Research shows that smokers are more likely to suffer from upper respiratory tract infection, pneumonia and other diseases. Smoking can also cause pulmonary inflammatory reactions, leading to airway stenosis and obstruction, seriously affecting respiratory function. Studying the role of smoking in promoting the formation of Atherosclerosis has important scientific and social significance, which helps to understand the relationship between smoking and Atherosclerosis, provides scientific basis and guidance, promotes health publicity and education, and improves public health.

Common Carotid Artery Stenosis Degree as a Predictor of Cardiovascular Disease in a General Population: The Suita Study.

The utility of screening for the degree of common carotid artery (CCA) stenosis as a predictor of cardiovascular disease (CVD) in a general population remains unclear. We studied 4775 Japanese men and women whose CCA was measured using bilateral carotid ultrasonography at baseline (April 1994-August 2001). We calculated the degree of stenosis as a percentage of the stenotic area of the lumen in the cross-section perpendicular to the long axis. The Cox proportional hazards model was used to calculate multivariable-adjusted hazard ratios (HRs) with 95% CIs for incident CVD and its subtypes according to the degree of CCA stenosis. During the median 14.2 years of follow-up, 385 incident CVD events (159 coronary heart disease and 226 stroke) were documented. The degree of CCA stenosis was associated with increased risks of incident CVD, coronary heart disease, and stroke, with multivariable-adjusted HRs (95% CIs) for <25%, 25%-49%, and ≥50% stenosis with plaque compared with no CCA plaque of 1.37 (1.07-1.76), 1.72 (1.23-2.40), and 2.49 (1.69-3.67), respectively. Adding the CCA stenosis degree to traditional CVD risk factors increased Harrell's C statistics (0.772 [95% CI, 0.751-0.794] to 0.778 [95% CI, 0.758-0.799]; P=0.04) and improved the 10-year risk prediction ability (integrated discrimination improvement, 0.0129 [95% CI, 0.0078-0.0179]; P<0.001; continuous net reclassification improvement, 0.1598 [95% CI, 0.0297-0.2881]; P=0.01). The degree of CCA stenosis may be used as a predictive marker for the development of CVD in the general population.

Upregulation of Hsp27 via further inhibition of histone H2A ubiquitination confers protection against myocardial ischemia/reperfusion injury by promoting glycolysis and enhancing mitochondrial function

Research suggests that ischemic glycolysis improves myocardial tolerance to anoxia and low-flow ischemia. The rate of glycolysis during ischemia reflects the severity of the injury caused by ischemia and subsequent functional recovery following reperfusion. Histone H2AK119 ubiquitination (H2Aub) is a common modification that is primarily associated with gene silencing. Recent studies have demonstrated that H2Aub contributes to the development of cardiovascular diseases. However, the underlying mechanism remains unclear. This study identified Hsp27 (heat shock protein 27) as a H2Aub binding protein and explored its involvement in mediating glycolysis and mitochondrial function. Functional studies revealed that inhibition of PRC1 (polycomb repressive complex 1) decreased H2Aub occupancy and promoted Hsp27 expression through inhibiting ubiquitination. Additionally, it increased glycolysis by activating the NF-κB/PFKFB3 signaling pathway during myocardial ischemia. Furthermore, Hsp27 reduced mitochondrial ROS production by chaperoning COQ9, and suppressed ferroptosis during reperfusion. A delivery system was developed based on PCL-PEG-MAL (PPM)-PCM-SH (CWLSEAGPVVTVRALRGTGSW) to deliver PRT4165 (PRT), a potent inhibitor of PRC1, to damaged myocardium, resulting in decreased H2Aub. These findings revealed a novel epigenetic mechanism connecting glycolysis and ferroptosis in protecting the myocardium against ischemia/reperfusion injury.

Unraveling the role of galectin-3 in cardiac pathology and physiology.

Galectin-3 (Gal-3) is a carbohydrate-binding protein with multiple functions. Gal-3 regulates cell growth, proliferation, and apoptosis by orchestrating cell-cell and cell-matrix interactions. It is implicated in the development and progression of cardiovascular disease, and its expression is increased in patients with heart failure. In atherosclerosis, Gal-3 promotes monocyte recruitment to the arterial wall boosting inflammation and atheroma. In acute myocardial infarction (AMI), the expression of Gal-3 increases in infarcted and remote zones from the beginning of AMI, and plays a critical role in macrophage infiltration, differentiation to M1 phenotype, inflammation and interstitial fibrosis through collagen synthesis. Genetic deficiency of Gal-3 delays wound healing, impairs cardiac remodeling and function after AMI. On the contrary, Gal-3 deficiency shows opposite results with improved remodeling and function in other cardiomyopathies and in hypertension. Pharmacologic inhibition with non-selective inhibitors is also protective in cardiac disease. Finally, we recently showed that Gal-3 participates in normal aging. However, genetic absence of Gal-3 in aged mice exacerbates pathological hypertrophy and increases fibrosis, as opposed to reduced fibrosis shown in cardiac disease. Despite some gaps in understanding its precise mechanisms of action, Gal-3 represents a potential therapeutic target for the treatment of cardiovascular diseases and the management of cardiac aging. In this review, we summarize the current knowledge regarding the role of Gal-3 in the pathophysiology of heart failure, atherosclerosis, hypertension, myocarditis, and ischemic heart disease. Furthermore, we describe the physiological role of Gal-3 in cardiac aging.

Endogenous SIRT6 in platelets negatively regulates platelet activation and thrombosis.

Thromboembolism resulting from platelet dysfunction constitutes a significant contributor to the development of cardiovascular disease. Sirtuin 6 (SIRT6), an essential NAD+-dependent enzyme, has been linked to arterial thrombosis when absent in endothelial cells. In the present study, we have confirmed the presence of SIRT6 protein in anucleated platelets. However, the precise regulatory role of platelet endogenous SIRT6 in platelet activation and thrombotic processes has remained uncertain. Herein, we present compelling evidence demonstrating that platelets isolated from SIRT6-knockout mice (SIRT6-/-) exhibit a notable augmentation in thrombin-induced platelet activation, aggregation, and clot retraction. In contrast, activation of SIRT6 through specific agonist treatment (UBCS039) confers a pronounced protective effect on platelet activation and arterial thrombosis. Moreover, in platelet adoptive transfer experiments between wild-type (WT) and SIRT6-/- mice, the loss of SIRT6 in platelets significantly prolongs the mean thrombus occlusion time in a FeCl3-induced arterial thrombosis mouse model. Mechanistically, we have identified that SIRT6 deficiency in platelets leads to the enhanced expression and release of proprotein convertase subtilisin/kexin type 9 (PCSK9), subsequently activating the platelet activation-associated mitogen-activated protein kinase (MAPK) signaling pathway. These findings collectively unveil a novel protective role of platelet endogenous SIRT6 in platelet activation and thrombosis. This protective effect is, at least in part, attributed to the inhibition of platelet PCSK9 secretion and mitogen-activated protein kinase signaling transduction. Our study provides valuable insights into the intricate interplay between SIRT6 and platelet function, shedding light on potential therapeutic avenues for managing thrombotic disorders.

Central stress pathways in the development of cardiovascular disease.

Mental stress is of essential consideration when assessing cardiovascular pathophysiology in all patient populations. Substantial evidence indicates associations among stress, cardiovascular disease and aberrant brain-body communication. However, our understanding of the flow of stress information in humans, is limited, despite the crucial insights this area may offer into future therapeutic targets for clinical intervention. Key terms including mental stress, cardiovascular disease and central control, were searched in PubMed, ScienceDirect and Scopus databases. Articles indicative of heart rate and blood pressure regulation, or central control of cardiovascular disease through direct neural innervation of the cardiac, splanchnic and vascular regions were included. Focus on human neuroimaging research and the flow of stress information is described, before brain-body connectivity, via pre-motor brainstem intermediates is discussed. Lastly, we review current understandings of pathophysiological stress and cardiovascular disease aetiology. Structural and functional changes to corticolimbic circuitry encode stress information, integrated by the hypothalamus and amygdala. Pre-autonomic brain-body relays to brainstem and spinal cord nuclei establish dysautonomia and lead to alterations in baroreflex functioning, firing of the sympathetic fibres, cellular reuptake of norepinephrine and withdrawal of the parasympathetic reflex. The combined result is profoundly adrenergic and increases the likelihood of cardiac myopathy, arrhythmogenesis, coronary ischaemia, hypertension and the overall risk of future sudden stress-induced heart failure. There is undeniable support that mental stress contributes to the development of cardiovascular disease. The emerging accumulation of large-scale multimodal neuroimaging data analytics to assess this relationship promises exciting novel therapeutic targets for future cardiovascular disease detection and prevention.

A mother’s diet as a predictor of her child’s current and future health

The body’s ‘nutritional programming’ scheme assumes that the influence of environmental factors during the so-called “critical periods’” of human development associated with, among other things, excessive or deficient nutrients can lead to permanent metabolic changes. The negative impact of external factors, poor nutrition, different gene expression during the fetal period with accompanying fetal growth retardation can permanently “reprogram” the metabolism and the course of many physiological processes, causing metabolic complications in adulthood. More and more researchers and theoreticians are considering and verifying the relationship between the early influence of environmental factors and the occurrence of civilisation diseases in the context of nutritional programming. Recently, many researchers have pointed out that the infant years are a critical time for metabolic programming. The impact of a pregnant woman’s nutrition on the development of obesity, cardiovascular disease, insulin resistance or metabolic syndrome in her child’s later life has been empirically proven. Similar results have been reported for the importance of breastfeeding and also of nutritional deficiencies or excesses in the first 1000 days of the child. This period is particularly susceptible to all the factors that affect the body and builds the foundations of the child’s broader health at present and in the future. The aim of this study is to show, on the basis of an analysis of research reports, that both woman’s nutrition during the pre-conceptional period and during pregnancy, as well as her child’s nutrition after birth, are of crucial importance for the child’s development and somatic health. Keywords: child health, feeding, metabolic programming, nutrition, pregnancy.

Inflammageing mediated by cytotoxic lymphocytes is associated with diabetes duration

AimsInflammageing, the age-related systemic increase of proinflammatory factors, has been linked to the development of cardiovascular disease, chronic kidney disease and cancer in the elderly. Chronic inflammation is believed to be a causative factor in the development of diabetic complications. However, exactly how type 2 diabetes impacts the inflammatory state of the immune system is incompletely characterised. MethodsBlood collection and anthropometric measurements were performed in patients with type 2 diabetes (n=49) and control subjects (n=30). The phenotype, proliferation capacity and cytokine production by cytotoxic lymphocytes were analysed using multiparametric flow cytometry. ResultsType 2 diabetes did not impact the phenotype or proliferation of the investigated cells. However, we observed a significantly increased production of tumour necrosis factor-α by CD8+ T cells and Granzyme B by natural killer cells and γδ T cells compared to controls. Hyperresponsiveness of cytotoxic blood lymphocytes did not correlate with glycaemia or body mass index, but instead was associated with older age and longer diabetes duration. ConclusionsType 2 diabetes is associated with an increased pro-inflammatory potential of cytotoxic blood lymphocytes correlating with age and diabetes duration. Further research is necessary to explore potential benefits of diabetes medications in reverting this effect.

Circular RNA: A new expectation for cardiovascular diseases.

Circular RNA (circRNA) is a class of RNA with the 5' and 3' ends connected covalently to form a closed loop structure and characterized by high stability, conserved sequences and tissue specificity, which is caused by special reverse splicing methods. Currently, it has become a hot spot for research. With the discovery of its powerful regulatory functions and roles, the molecular mechanisms and future value of circRNA in participating in and regulating biological and pathological processes are becoming increasingly apparent. Among them is the increasing prevalence of cardiovascular diseases (CVDs). Many studies have elucidated that circRNA plays a crucial role in the development and progression of CVDs. Therefore, circRNA shows its advantages and brilliant expectations in the field of CVDs. In this review, we describe the biogenesis, bioinformatics detection and function of circRNA and discuss the role of circRNA and its effects on CVDs, including atherosclerosis, myocardial infarction, cardiac hypertrophy and heart failure, myocardial fibrosis, cardiac senescence, pulmonary hypertension, and diabetic cardiomyopathy by different mechanisms. That shows circRNA advantages and brilliant expectations in the field of CVDs.

Transcriptome-wide N6-methyladenosine methylation profile of atherosclerosis in mice

BackgroundAtherosclerosis (AS) is a critical pathological event during the progression of cardiovascular diseases. It exhibits fibrofatty lesions on the arterial wall and lacks effective treatment. N6-methyladenosine (m6A) is the most common modification of eukaryotic RNA and plays an important role in regulating the development and progression of cardiovascular diseases. However, the role of m6A modification in AS remains largely unknown. Therefore, in this study, we explored the transcriptome distribution of m6A modification in AS and its potential mechanism.MethodsMethylation Quantification Kit was used to detect the global m6A levels in the aorta of AS mice. Western blot was used to analyze the protein level of methyltransferases. Methylated RNA immunoprecipitation with next-generation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) were used to obtain the first transcriptome range analysis of the m6A methylene map in the aorta of AS mice, followed by bioinformatics analysis. qRT-PCR and MeRIP-qRT-PCR were used to measure the mRNA and m6A levels in target genes.ResultsThe global m6A and protein levels of methyltransferase METTL3 were significantly increased in the aorta of AS mice. However, the protein level of demethylase ALKBH5 was significantly decreased. Through MeRIP-seq, we obtained m6A methylation maps in AS and control mice. In total, 26,918 m6A peaks associated with 13,744 genes were detected in AS group, whereas 26,157 m6A peaks associated with 13,283 genes were detected in the control group. Peaks mainly appeared in the coding sequence (CDS) regions close to the stop codon with the RRACH motif. Moreover, functional enrichment analysis demonstrated that m6A-containing genes were significantly enriched in AS-relevant pathways. Interestingly, a negative correlation between m6A methylation abundance and gene expression level was found through the integrated analysis of MeRIP-seq and RNA-seq data. Among the m6A-modified genes, a hypo-methylated but up-regulated (hypo-up) gene Fabp5 may be a potential biomarker of AS.ConclusionsOur study provides transcriptome-wide m6A methylation for the first time to determine the association between m6A modification and AS progression. Our study lays a foundation for further exploring the pathogenesis of AS and provides a new direction for the treatment of AS.

Trafficking and effect of released DNA on cGAS-STING signaling pathway and cardiovascular disease.

Evidence from clinical research and animal studies indicates that inflammation is an important factor in the occurrence and development of cardiovascular disease (CVD). Emerging evidence shows that nucleic acids serve as crucial pathogen-associated molecular patterns (PAMPs) or non-infectious damage-associated molecular patterns (DAMPs), are released and then recognized by pattern recognition receptors (PRRs), which activates immunological signaling pathways for host defense. Mechanistically, the released nucleic acids activate cyclic GMP-AMP synthase (cGAS) and its downstream receptor stimulator of interferon genes (STING) to promote type I interferons (IFNs) production, which play an important regulatory function during the initiation of an innate immune response to various diseases, including CVD. This pathway represents an essential defense regulatory mechanism in an organism's innate immune system. In this review, we outline the overall profile of cGAS-STING signaling, summarize the latest findings on nucleic acid release and trafficking, and discuss their potential role in CVD. This review also sheds light on potential directions for future investigations on CVD.

FIDELIO study: significance and place of finerenone as nonsteroidal mineralocorticoid receptor antagonist in therapy of patients with chronic kidney disease in type 2 diabetes

Patients with diabetes mellitus and renal pathology are at high risk of developing end-stage kidney disease (ESKD) and cardiovascular disease (CVD), including atrial fibrillation as an life-threatening condition. The intense annual increase in patients with diabetes mellitus, mainly due to the patients with type 2 diabetes mellitus (T2D), and diabetic nephropathy sets a new goal for researchers to expand the range of drugs with cardio- and nephroprotective effects to offset the residual risks of development and progression of chronic kidney disease (CKD) and CVD in this cohort of patients. One of such drugs is finerenone — a novel selective non-steroidal mineralocorticoid receptor (MR) antagonist (MRA), hyperactivation of which mediates renal inflammation and fibrosis, cardiac remodeling and changes in its structural and electrical characteristics. This review presents the results of the sub-analysis of FIDELIO devoted to the mechanism of drug action, the finerenone efficacy evaluation, its comparison with the efficacy of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists with already proven organoprotective properties with respect to reducing the risk of renal and cardiovascular endpoints.

Cannabis use and atherosclerotic cardiovascular disease: a Mendelian randomization study

BackgroundAssociation between cannabis use and development of atherosclerotic cardiovascular disease (ASCVD) is inconsistent and challenging to interpret, given existing study limitations.MethodsSixty five independent single-nucleotide polymorphisms (SNPs), obtained from a genome-wide association study on lifetime cannabis use, were employed as genetic instruments to estimate the effects of genetically indexed cannabis use on risk of coronary artery disease (CAD) and acute ischemic stroke (IS) using a two-sample Mendelian randomization (MR) approach. Summary statistics on CAD (CARDIoGRAMplusC4D; 60,801 cases and 123,504 controls) and IS (MEGASTROKE; 34,217 cases and 406,111 controls) were obtained separately. A comprehensive review of the observational literature on cannabis use and CAD or IS was also performed and contrasted with MR results.ResultsThere was no causal effect of cannabis use on the risk of CAD (odds ratio (OR) per ever-users vs. never-users 0.93; 95% confidence interval (CI), 0.83 to 1.03) or IS (OR 1.05; 95%CI, 0.93 to 1.19). Sensitivity analyses yielded similar results, and no heterogeneity and directional pleiotropy was observed. Our meta-analysis of observational studies showed no significant association between ever use of cannabis with risk of CAD (k = 6 studies; ORpooled = 1.23, 95%CI 0.78 to 1.69), nor with IS (k = 6 studies; ORpooled = 1.22, 95%CI 0.95 to 1.50).ConclusionUsing a genetic approach approximating a clinical trial does not provide evidence consistent with a causal effect of genetic predisposition to cannabis use on CAD or IS development. Further studies are needed to replicate our findinds, an to investigate more precisely the risk of ASCVD in relation to the quantity, type, route of administration, or the age at exposure to cannabis.

Gut-immune axis and cardiovascular risk in chronic kidney disease.

Patients with chronic kidney disease (CKD) suffer from marked cardiovascular morbidity and mortality, so lowering the cardiovascular risk is paramount to improve quality of life and survival in CKD. Manifold mechanisms are hold accountable for the development of cardiovascular disease (CVD), and recently inflammation arose as novel risk factor significantly contributing to progression of CVD. While the gut microbiome was identified as key regulator of immunity and inflammation in several disease, CKD-related microbiome-immune interaction gains increasing importance. Here, we summarize the latest knowledge on microbiome dysbiosis in CKD, subsequent changes in bacterial and host metabolism and how this drives inflammation and CVD in CKD. Moreover, we outline potential therapeutic targets along the gut-immune-cardiovascular axis that could aid the combat of CVD development and high mortality in CKD.

Evaluation of Macular and Optic Disc Radial Peripapillary Vessel Density Using Optical Coherence Tomography Angiography in Gout Patients.

In this cross-sectional study, optical coherence tomography angiography (OCT-A) findings were compared in patients with gout (n = 30) and healthy participants (n = 32). The superficial and deep vessel density variables measured using OCT-A were compared between the groups. The superficial foveal and perifoveal vessel densities of the patient group were lower than those of the healthy participants (p = 0.014 and p = 0.045, respectively). However, all superficial and parafoveal vessel densities were similar in both groups (p = 0.469 and p = 0.284, respectively). The deep capillary plexus density measurements of the whole-zone, foveal, parafoveal, and perifoveal vessel densities using OCT-A revealed no significant differences between the groups (p = 0.251, p = 0.074, p = 0.177, and p = 0.881, respectively). A higher serum uric acid (SUA) level was found to be independently associated with a decreased superficial capillary plexus density and an increased choriocapillary flow deficit in the study population. Men were less sensitive to high SUA levels than women. These findings suggest that an elevated uric acid concentration may play a role in the development and progression of cardiovascular disease through changes in the microvasculature, as shown by the OCT-A parameters.

Galectin-3 and its correlation with carotid ultrasound in rheumatoid arthritis patients

BackgroundRheumatoid arthritis (RA) is a chronic inflammatory disease resulting in disability as well as joint damage. Early diagnosis and treatment are crucial for improving outcomes. RA patients have a twofold elevated risk of cardiovascular disease (CVD) development compared to the general population. Carotid ultrasound is a noninvasive imaging modality that can detect early signs of atherosclerosis and plaque buildup in the carotid arteries, which are strongly associated with CVD risk. Galectin-3 (Gal-3), a protein involved in inflammation and fibrosis, is suggested as one of the potential RA markers. Despite the growing interest in galectin-3 as a biomarker for CVD, few studies have investigated its role in RA patients. To our knowledge, only two studies have examined the correlation between galectin-3 and CVD in RA patients, and they have yielded conflicting results. This study aimed to determine the serum level of Gal-3 as well as its correlation with carotid ultrasound assessment for cardiovascular involvement in RA patients.ResultsRA cases demonstrated substantially elevated Gal-3 levels than controls (P < 0.001), and a 3.38 pg/mL cut-off value was proven to be an excellent predictor of RA diagnosis (AUC, 0.98). Gal-3 levels were proven to be positively associated with DAS-28, Larsen score, and carotid intima-media thickness (CIMT) (P-value 0.006, 0.026, < 0.001, respectively). A positive association was also detected between right (RT) and left (LT) CIMT and disease duration (P-values of 0.040 and 0.042, respectively).ConclusionsGal-3 is a biomarker for RA that is not only associated with activity and severity of the disease but it is also related to the chronicity of the disease and is a predictor of cardiovascular comorbidity.

Myeloid SENP3 deficiency protects mice from diet and age-induced obesity via regulation of YAP1 SUMOylation

Obesity is characterized by chronic low-grade inflammation, which is driven by macrophage infiltration in adipose tissue and leads to elevated cytokines such as interleukin-1β (IL-1β) in the circulation and tissues. Previous studies demonstrate that SENP3, a redox-sensitive SUMO2/3-specific protease, is strongly implicated in the development and progression of cancer and cardiovascular diseases. However, the role of SENP3 in obesity-associated inflammation remains largely unknown. To better understand the effects of SENP3 on adipose tissue macrophage (ATM) activation and function within the context of obesity, we generated mice with myeloid-specific deletion of SENP3 (Senp3flox/flox;Lyz2-Cre mice). We found that the expression of SENP3 is dramatically increased in ATMs during high-fat diet (HFD)-induced obesity in mice. Senp3flox/flox;Lyz2-Cre mice show lower body weight gain and reduced adiposity and adipocyte size after challenged with HFD and during aging. Myeloid-specific SENP3 deletion attenuates macrophage infiltration in adipose tissue and reduces serum levels of inflammatory factors during diet and age-induced obesity. Furthermore, we found that SENP3 knockout markedly inhibits cytokine release from macrophage after lipopolysaccharide and palmitic acid treatment in vitro. Mechanistically, in cultured peritoneal macrophages, SENP3 protein level is enhanced by IL-1β, in parallel with the upregulation of Yes-associated protein 1 (YAP1). Moreover, we demonstrated that SENP3 modulates de-SUMO modification of YAP1 and SENP3 deletion abolishes the upregulation of YAP1 induced by IL-1β. Most importantly, SENP3 deficiency reduces YAP1 protein level in adipose tissue during obesity. Our results highlight the important role of SENP3 in ATM inflammation and diet and age-induced obesity.

Noncoding RNAs regulating ferroptosis in cardiovascular diseases: novel roles and therapeutic strategies

AbstractThe morbidity and mortality rates of cardiovascular diseases (CVDs) are increasing; thus, they impose substantial health and economic burdens worldwide, and effective interventions are needed for immediate resolution of this issue. Recent studies have suggested that noncoding RNAs (ncRNAs) play critical roles in the occurrence and development of CVDs and are potential therapeutic targets and novel biomarkers for these diseases. Newly discovered modes of cell death, including necroptosis, pyroptosis, apoptosis, autophagy-dependent cell death and ferroptosis, also play key roles in CVD progression. However, ferroptosis, which differs from the other aforementioned forms of regulated cell death in terms of cell morphology, biochemistry and inhereditability, is a unique iron-dependent mode of nonapoptotic cell death induced by abnormal iron metabolism and excessive accumulation of iron-dependent lipid peroxides and reactive oxygen species (ROS). Increasing evidence has confirmed that ncRNA-mediated ferroptosis is involved in regulating tissue homeostasis and CVD-related pathophysiological conditions, such as cardiac ischemia/reperfusion (I/R) injury, myocardial infarction (MI), atrial fibrillation (AF), cardiomyopathy and heart failure (HF). In this review, we summarize the underlying mechanism of ferroptosis, discuss the pathophysiological effects of ncRNA-mediated ferroptosis in CVDs and provide ideas for effective therapeutic strategies.