Circular RNA in cardiovascular disease Altesha, M‐Ashraf; Ni, Tiffany; Khan, Afaan ...
Journal of cellular physiology,
20/May , Volume:
234, Issue:
5
Journal Article
Peer reviewed
Circular RNA (circRNA) are endogenous transcripts that display differential expression across species, developmental stages, and pathologies. Their lack of free ends confers increased stability when ...compared with linear transcripts, making them ideal candidates for future diagnostic biomarkers and therapeutic interventions. Increasing evidence has implicated circRNA in the pathogenesis of multiple cardiovascular diseases. In this paper, we summarize current understanding of circRNA biogenesis, properties, expression profiles, detection methods, functions, and their implication in cardiac pathologies including/ischemia reperfusion injury, myocardial infarction, cardiac senescence, cardiac fibrosis, cardiomyopathy, cardiac hypertrophy and heart failure, atherosclerosis, coronary artery disease, and aneurysm.
Increasing evidence has implicated circular RNA (circRNA) in the pathogenesis of multiple cardiovascular diseases.This review provides scientists and clinicians with a brief summary of the ever‐growing world of circRNAs and their role in cardiac diseases specifically.
Cardiovascular disease (CVD) presents a great burden for elderly patients, their caregivers, and health systems. Structural and functional alterations of vessels accumulate throughout life, ...culminating in increased risk of developing CVD. The growing elderly population worldwide highlights the need to understand how aging promotes CVD in order to develop new strategies to confront this challenge. This review provides examples of some major unresolved clinical problems encountered in daily cardiovascular practice as we care for elderly patients. Next, the authors summarize the current understanding of the mechanisms implicated in cardiovascular aging, and the potential for targeting novel pathways implicated in endothelial dysfunction, mitochondrial oxidative stress, chromatin remodeling, and genomic instability. Lastly, the authors consider critical aspects of vascular repair, including autologous transplantation of bone marrow-derived stem cells in elderly patients.
Precision medicine is an integrative approach to cardiovascular disease prevention and treatment that considers an individual's genetics, lifestyle, and exposures as determinants of their ...cardiovascular health and disease phenotypes. This focus overcomes the limitations of reductionism in medicine, which presumes that all patients with the same signs of disease share a common pathophenotype and, therefore, should be treated similarly. Precision medicine incorporates standard clinical and health record data with advanced panomics (ie, transcriptomics, epigenomics, proteomics, metabolomics, and microbiomics) for deep phenotyping. These phenotypic data can then be analyzed within the framework of molecular interaction (interactome) networks to uncover previously unrecognized disease phenotypes and relationships between diseases, and to select pharmacotherapeutics or identify potential protein-drug or drug-drug interactions. In this review, we discuss the current spectrum of cardiovascular health and disease, population averages and the response of extreme phenotypes to interventions, and population-based versus high-risk treatment strategies as a pretext to understanding a precision medicine approach to cardiovascular disease prevention and therapeutic interventions. We also consider the search for resilience and Mendelian disease genes and argue against the theory of a single causal gene/gene product as a mediator of the cardiovascular disease phenotype, as well as an Erlichian magic bullet to solve cardiovascular disease. Finally, we detail the importance of deep phenotyping and interactome networks and the use of this information for rational polypharmacy. These topics highlight the urgent need for precise phenotyping to advance precision medicine as a strategy to improve cardiovascular health and prevent disease.
High dietary intake or blood concentrations (as biomarkers of dietary intake) of vitamin C, carotenoids, and vitamin E have been associated with reduced risk of cardiovascular disease, cancer, and ...mortality, but these associations have not been systematically assessed.
We conducted a systematic review and meta-analysis of prospective studies of dietary intake and blood concentrations of vitamin C, carotenoids, and vitamin E in relation to these outcomes.
We searched PubMed and Embase up to 14 February 2018. Summary RRs and 95% CIs were calculated with the use of random-effects models.
Sixty-nine prospective studies (99 publications) were included. The summary RR per 100-mg/d increment of dietary vitamin C intake was 0.88 (95% CI: 0.79, 0.98, I2= 65%, n = 11) for coronary heart disease, 0.92 (95% CI: 0.87, 0.98, I2= 68%, n = 12) for stroke, 0.89 (95% CI: 0.85, 0.94, I2= 27%, n = 10) for cardiovascular disease, 0.93 (95% CI: 0.87, 0.99, I2= 46%, n = 8) for total cancer, and 0.89 (95% CI: 0.85, 0.94, I2= 80%, n = 14) for all-cause mortality. Corresponding RRs per 50-μmol/L increase in blood concentrations of vitamin C were 0.74 (95% CI: 0.65, 0.83, I2= 0%, n = 4), 0.70 (95% CI: 0.61, 0.81, I2= 0%, n = 4), 0.76 (95% CI: 0.65, 0.87, I2= 56%, n = 6), 0.74 (95% CI: 0.66, 0.82, I2= 0%, n = 5), and 0.72 (95% CI: 0.66, 0.79, I2= 0%, n = 8). Dietary intake and/or blood concentrations of carotenoids (total, β-carotene, α-carotene, β-cryptoxanthin, lycopene) and α-tocopherol, but not dietary vitamin E, were similarly inversely associated with coronary heart disease, stroke, cardiovascular disease, cancer, and/or all-cause mortality.
Higher dietary intake and/or blood concentrations of vitamin C, carotenoids, and α-tocopherol (as markers of fruit and vegetable intake) were associated with reduced risk of cardiovascular disease, total cancer, and all-cause mortality. These results support recommendations to increase fruit and vegetable intake, but not antioxidant supplement use, for chronic disease prevention.
Obstructive sleep apnea (OSA) is characterized by recurrent complete and partial upper airway obstructive events, resulting in intermittent hypoxemia, autonomic fluctuation, and sleep fragmentation. ...Approximately 34% and 17% of middle-aged men and women, respectively, meet the diagnostic criteria for OSA. Sleep disturbances are common and underdiagnosed among middle-aged and older adults, and the prevalence varies by race/ethnicity, sex, and obesity status. OSA prevalence is as high as 40% to 80% in patients with hypertension, heart failure, coronary artery disease, pulmonary hypertension, atrial fibrillation, and stroke. Despite its high prevalence in patients with heart disease and the vulnerability of cardiac patients to OSA-related stressors and adverse cardiovascular outcomes, OSA is often underrecognized and undertreated in cardiovascular practice. We recommend screening for OSA in patients with resistant/poorly controlled hypertension, pulmonary hypertension, and recurrent atrial fibrillation after either cardioversion or ablation. In patients with New York Heart Association class II to IV heart failure and suspicion of sleep-disordered breathing or excessive daytime sleepiness, a formal sleep assessment is reasonable. In patients with tachy-brady syndrome or ventricular tachycardia or survivors of sudden cardiac death in whom sleep apnea is suspected after a comprehensive sleep assessment, evaluation for sleep apnea should be considered. After stroke, clinical equipoise exists with respect to screening and treatment. Patients with nocturnally occurring angina, myocardial infarction, arrhythmias, or appropriate shocks from implanted cardioverter-defibrillators may be especially likely to have comorbid sleep apnea. All patients with OSA should be considered for treatment, including behavioral modifications and weight loss as indicated. Continuous positive airway pressure should be offered to patients with severe OSA, whereas oral appliances can be considered for those with mild to moderate OSA or for continuous positive airway pressure-intolerant patients. Follow-up sleep testing should be performed to assess the effectiveness of treatment.
Cardiovascular diseases (CVDs), consisting of ischemic heart disease, stroke, heart failure, peripheral arterial disease, and a number of other cardiac and vascular conditions, constitute the leading ...cause of global mortality and are a major contributor to reduced quality of life (1,2). ...how are we monitoring these global and regional trends, and how are they informing cardiology practice, health policy, and clinical research? ...recently, comprehensive assessments of summary measures of health and related data from internally consistent, systematic, and comparable methodology for all diseases, injuries, and risk factors were not readily available. For the risk factors, subcategory data will be presented for high blood pressure, high low-density lipoprotein cholesterol, high fasting plasma glucose, high body mass index, air pollution (including ambient and household), tobacco use (including smoking and secondhand), impaired kidney function, lead exposure, alcohol use, and dietary targets of health policy.
Higher intake of marine n-3 (also called omega-3) fatty acids has been associated with reduced risks of cardiovascular disease and cancer in several observational studies. Whether supplementation ...with n-3 fatty acids has such effects in general populations at usual risk for these end points is unclear.
We conducted a randomized, placebo-controlled trial, with a two-by-two factorial design, of vitamin D
(at a dose of 2000 IU per day) and marine n-3 fatty acids (at a dose of 1 g per day) in the primary prevention of cardiovascular disease and cancer among men 50 years of age or older and women 55 years of age or older in the United States. Primary end points were major cardiovascular events (a composite of myocardial infarction, stroke, or death from cardiovascular causes) and invasive cancer of any type. Secondary end points included individual components of the composite cardiovascular end point, the composite end point plus coronary revascularization (expanded composite of cardiovascular events), site-specific cancers, and death from cancer. Safety was also assessed. This article reports the results of the comparison of n-3 fatty acids with placebo.
A total of 25,871 participants, including 5106 black participants, underwent randomization. During a median follow-up of 5.3 years, a major cardiovascular event occurred in 386 participants in the n-3 group and in 419 in the placebo group (hazard ratio, 0.92; 95% confidence interval CI, 0.80 to 1.06; P=0.24). Invasive cancer was diagnosed in 820 participants in the n-3 group and in 797 in the placebo group (hazard ratio, 1.03; 95% CI, 0.93 to 1.13; P=0.56). In the analyses of key secondary end points, the hazard ratios were as follows: for the expanded composite end point of cardiovascular events, 0.93 (95% CI, 0.82 to 1.04); for total myocardial infarction, 0.72 (95% CI, 0.59 to 0.90); for total stroke, 1.04 (95% CI, 0.83 to 1.31); for death from cardiovascular causes, 0.96 (95% CI, 0.76 to 1.21); and for death from cancer (341 deaths from cancer), 0.97 (95% CI, 0.79 to 1.20). In the analysis of death from any cause (978 deaths overall), the hazard ratio was 1.02 (95% CI, 0.90 to 1.15). No excess risks of bleeding or other serious adverse events were observed.
Supplementation with n-3 fatty acids did not result in a lower incidence of major cardiovascular events or cancer than placebo. (Funded by the National Institutes of Health and others; VITAL ClinicalTrials.gov number, NCT01169259 .).
Obesity is associated with an increased risk of developing cardiovascular disease (CVD), particularly heart failure (HF) and coronary heart disease (CHD). The mechanisms through which obesity ...increases CVD risk involve changes in body composition that can affect hemodynamics and alters heart structure. Pro-inflammatory cytokines produced by the adipose tissue itself which can induce cardiac dysfunction and can promote the formation of atherosclerotic plaques. When obesity and HF or CHD coexist, individuals with class I obesity present a more favorable prognosis compared to individuals who are normal or underweight. This phenomenon has been termed the "obesity paradox." Obesity is defined as an excess fat mass (FM), but individuals with obesity typically also present with an increased amount of lean mass (LM). The increase in LM may explain part of the obesity paradox as it is associated with improved cardiorespiratory fitness (CRF), a major determinant of clinical outcomes in the general population, but particularly in those with CVD, including HF. While increased LM is a stronger prognosticator in HF compared to FM, in patients with CHD excess FM can exert protective effects particularly when not associated with increased systemic inflammation. In the present review, we discuss the mechanisms through which obesity may increase the risk for CVD, and how it may exert protective effects in the setting of established CVD, with a focus on body composition. We also highlight the importance of measuring or estimating CRF, including body composition-adjusted measures of CRF (ie, lean peak oxygen consumption) for an improved risk status stratification in patients with CVD and finally, we discuss the potential non-pharmacologic therapeutics, such as exercise training and dietary interventions, aimed at improving CRF and perhaps clinical outcomes.
Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality in the world. Although considerable progress has been made in the diagnosis, treatment and prognosis of CVD, there is ...still a critical need for novel diagnostic biomarkers and new therapeutic interventions to decrease the incidence of this disease. Recently, there is increasing evidence that circulating miRNAs (miRNAs), i.e. endogenous, stable, single-stranded, short, non-coding RNAs, can be used as diagnostic biomarkers for CVD. Furthermore, miRNAs represent potential novel therapeutic targets for several cardiovascular disorders. In this review we provides an overview of the effects of several CVD; including heart failure, acute myocardial infarction, arrhythmias and pulmonary hypertension; on levels of circulating miRNAs. In addition, the use of miRNA as therapeutic targets is also discussed, as well as challenges and recommendations in their use in the diagnosis of CVD.
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