Role of Non-Coding RNA of Human Platelet in Cardiovascular Disease

2021 ◽  
Vol 29 ◽  
Author(s):  
Inzulza-Tapia A. ◽  
Alarcón M.

Abstract: Cardiovascular diseases (CVD) are the major cause of death in the world. Numerous genetic studies involving transcriptomic approaches aimed at the detailed understanding of the disease and the development of new therapeutic strategies have been conducted over recent years. There has been an increase in research on platelets, which are implicated in CVD due to their capacity to release regulatory molecules that affect various pathways. Platelets secrete over 500 various kinds of molecules to plasma including large amounts of non-coding (nc) RNA (miRNA, lncRNA or circRNA). These ncRNA correspond to 98% of transcripts that are not translated into proteins as they are important regulators in physiology and disease. Thus, miRNAs can direct protein complexes to mRNAs through base-pairing interactions, thus causing translation blockage or/and transcript degradation. The lncRNAs act via different mechanisms by binding to transcription factors. Finally, circRNAs act as regulators of miRNAs, interfering with their action. Alteration in the repertoire and/or the amount of the platelet-secreted ncRNA can trigger CVD as well as other diseases. NcRNAs can serve as effective biomarkers for the disease or as therapeutic targets due to their disease involvement. In this review, we will focus on the most important ncRNAs that are secreted by platelets (9 miRNA, 9 lncRNA and 5 circRNA), their association with CVD, and the contribution of these ncRNA to CVD risk to better understand the relation between ncRNA of human platelet and CVD.

2021 ◽  
Vol 29 (Supplement_1) ◽  
pp. i45-i46
Author(s):  
A Peletidi ◽  
R Kayyali

Abstract Introduction Obesity is one of the main cardiovascular disease (CVD) risk factors.(1) In primary care, pharmacists are in a unique position to offer weight management (WM) interventions. Greece is the European country with the highest number of pharmacies (84.06 pharmacies per 100,000 citizens).(2) The UK was chosen as a reference country, because of the structured public health services offered, the local knowledge and because it was considered to be the closest country to Greece geographically, unlike Australia and Canada, where there is also evidence confirming the potential role of pharmacists in WM. Aim To design and evaluate a 10-week WM programme offered by trained pharmacists in Patras. Methods This WM programme was a step ahead of other interventions worldwide as apart from the usual measuring parameters (weight, body mass index, waist circumference, blood pressure (BP)) it also offered an AUDIT-C and Mediterranean diet score tests. Results In total,117 individuals participated. Of those, 97.4% (n=114), achieved the programme’s aim, losing at least 5% of their initial weight. The mean % of total weight loss (10th week) was 8.97% (SD2.65), and the t-test showed statistically significant results (P<0.001; 95% CI [8.48, 9.45]). The programme also helped participants to reduce their waist-to-height ratio, an early indicator of the CVD risk in both male (P=0.004) and female (P<0.001) participants. Additionally, it improved participants’ BP, AUDIT-C score and physical activity levels significantly (P<0.001). Conclusion The research is the first systematic effort in Greece to initiate and explore the potential role of pharmacists in public health. The successful results of this WM programme constitute a first step towards the structured incorporation of pharmacists in public’s health promotion. It proposed a model for effectively delivering public health services in Greece. This study adds to the evidence in relation to pharmacists’ CVD role in public health with outcomes that superseded other pharmacy-led WM programmes. It also provides the first evidence that Greek pharmacists have the potential to play an important role within primary healthcare and that after training they are able to provide public health services for both the public’s benefit and their clinical role enhancement. This primary evidence should support the Panhellenic Pharmaceutical Association, to “fight” for their rights for an active role in primary care. In terms of limitations, it must be noted that the participants’ collected data were recorded by pharmacists, and the analysis therefore depended on the accuracy of the recorded data, in particular on the measurements or calculations obtained. Although the sample size was achieved, it can be argued that it is small for the generalisation of findings across Greece. Therefore, the WM programme should be offered in other Greek cities to identify if similar results can be replicated, so as to consolidate the contribution of pharmacists in promoting public health. Additionally, the study was limited as it did not include a control group. Despite the limitations, our findings provide a model for a pharmacy-led public health programme revolving around WM that can be used as a model for services in the future. References 1. Mendis S, Puska P, Norrving B, World Health Organization., World Heart Federation., World Stroke Organization. Global atlas on cardiovascular disease prevention and control [Internet]. Geneva: World Health Organization in collaboration with the World Heart Federation and the World Stroke Organization; 2011 [cited 2018 Jun 26]. 155 p. Available from: http://www.who.int/cardiovascular_diseases/publications/atlas_cvd/en/ 2. Pharmaceutical Group of the European Union. Pharmacy with you throughout life:PGEU Annual Report [Internet]. 2015. Available from: https://www.pgeu.eu/en/library/530:annual-report-2015.html


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Xueying Qin ◽  
Ida K. Karlsson ◽  
Yunzhang Wang ◽  
Xia Li ◽  
Nancy Pedersen ◽  
...  

Abstract Background Studies on DNA methylation have the potential to discover mechanisms of cardiovascular disease (CVD) risk. However, the role of DNA methylation in CVD etiology remains unclear. Results We performed an epigenome-wide association study (EWAS) on CVD in a longitudinal sample of Swedish twins (535 individuals). We selected CpGs reaching the Bonferroni-corrected significance level (2 $$\times$$ ×  10–7) or the top-ranked 20 CpGs with the lowest P values if they did not reach this significance level in EWAS analysis associated with non-stroke CVD, overall stroke, and ischemic stroke, respectively. We further applied a bivariate autoregressive latent trajectory model with structured residuals (ALT-SR) to evaluate the cross-lagged effect between DNA methylation of these CpGs and cardiometabolic traits (blood lipids, blood pressure, and body mass index). Furthermore, mediation analysis was performed to evaluate whether the cross-lagged effects had causal impacts on CVD. In the EWAS models, none of the CpGs we selected reached the Bonferroni-corrected significance level. The ALT-SR model showed that DNA methylation levels were more likely to predict the subsequent level of cardiometabolic traits rather than the other way around (numbers of significant cross-lagged paths of methylation → trait/trait → methylation were 84/4, 45/6, 66/1 for the identified three CpG sets, respectively). Finally, we demonstrated significant indirect effects from DNA methylation on CVD mediated by cardiometabolic traits. Conclusions We present evidence for a directional association from DNA methylation on cardiometabolic traits and CVD, rather than the opposite, highlighting the role of epigenetics in CVD development.


2016 ◽  
Vol 62 (4) ◽  
pp. 582-592 ◽  
Author(s):  
Miguel Ruiz-Canela ◽  
Estefania Toledo ◽  
Clary B Clish ◽  
Adela Hruby ◽  
Liming Liang ◽  
...  

Abstract BACKGROUND The role of branched-chain amino acids (BCAAs) in cardiovascular disease (CVD) remains poorly understood. We hypothesized that baseline BCAA concentrations predict future risk of CVD and that a Mediterranean diet (MedDiet) intervention may counteract this effect. METHODS We developed a case-cohort study within the Prevención con Dieta Mediterránea (PREDIMED), with 226 incident CVD cases and 744 noncases. We used LC-MS/MS to measure plasma BCAAs (leucine, isoleucine, and valine), both at baseline and after 1 year of follow-up. The primary outcome was a composite of incident stroke, myocardial infarction, or cardiovascular death. RESULTS After adjustment for potential confounders, baseline leucine and isoleucine concentrations were associated with higher CVD risk: the hazard ratios (HRs) for the highest vs lowest quartile were 1.70 (95% CI, 1.05–2.76) and 2.09 (1.27–3.44), respectively. Stronger associations were found for stroke. For both CVD and stroke, we found higher HRs across successive quartiles of BCAAs in the control group than in the MedDiet groups. With stroke as the outcome, a significant interaction (P = 0.009) between baseline BCAA score and intervention with MedDiet was observed. No significant effect of the intervention on 1-year changes in BCAAs or any association between 1-year changes in BCAAs and CVD were observed. CONCLUSIONS Higher concentrations of baseline BCAAs were associated with increased risk of CVD, especially stroke, in a high cardiovascular risk population. A Mediterranean-style diet had a negligible effect on 1-year changes in BCAAs, but it may counteract the harmful effects of BCAAs on stroke.


2020 ◽  
Vol 11 ◽  
Author(s):  
Lihui Chen ◽  
Jie Li ◽  
Wu Zhu ◽  
Yehong Kuang ◽  
Tao Liu ◽  
...  

Psoriasis affects the health of myriad populations around the world. The pathogenesis is multifactorial, and the exact driving factor remains unclear. This condition arises from the interaction between hyperproliferative keratinocytes and infiltrating immune cells, with poor prognosis and high recurrence. Better clinical treatments remain to be explored. There is much evidence that alterations in the skin and intestinal microbiome play an important role in the pathogenesis of psoriasis, and restoration of the microbiome is a promising preventive and therapeutic strategy for psoriasis. Herein, we have reviewed recent studies on the psoriasis-related microbiome in an attempt to confidently identify the “core” microbiome of psoriasis patients, understand the role of microbiome in the pathogenesis of psoriasis, and explore new therapeutic strategies for psoriasis through microbial intervention.


2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Dong Guo ◽  
Yuerong Xu ◽  
Jian Ding ◽  
Jiaying Dong ◽  
Ning Jia ◽  
...  

Despite substantial improvements in therapeutic strategies, cardiovascular disease (CVD) is still among the leading causes of mortality and morbidity worldwide. Exosomes, extracellular vesicles with a lipid bilayer membrane of endosomal origin, have been the focus of a large body of research in CVD. Exosomes not only serve as carriers for signal molecules responsible for intercellular and interorgan communication underlying CVD pathophysiology but also are bioactive agents which are partly responsible for the therapeutic effect of stem cell therapy of CVD. We here review recent insights gained into the role of exosomes in apoptosis, hypertrophy, angiogenesis, fibrosis, and inflammation in CVD pathophysiology and progression and the application and mechanisms of exosomes as therapeutic agents for CVD.


2004 ◽  
Vol 24 (20) ◽  
pp. 8938-8950 ◽  
Author(s):  
Linda B. Lingelbach ◽  
Kenneth B. Kaplan

ABSTRACT Sgt1p is a well-conserved protein proposed to be involved in a number of cellular processes. Genetic studies of budding yeast suggest a role for SGT1 in signal transduction, cell cycle advance, and chromosome segregation. Recent evidence has linked Sgt1p to HSP90 chaperones, although the precise relationship between these proteins is unclear. To further explore the role of Sgt1p in these processes, we have characterized the interactions among Sgt1p, the inner kinetochore complex CBF3, and HSP90 chaperones. We show that the amino terminus of Sgt1p interacts with CBF3 subunits Skp1p and Ctf13p. HSP90 interacts with Sgt1p and, in combination with the carboxy terminus of Sgt1p, regulates the interaction between Sgt1p and Skp1p in a nucleotide-dependent manner. While the Sgt1p-Skp1p interaction is required for CBF3 assembly, mutations that stabilize this interaction prevent the turnover of protein complexes important for CBF3 assembly. We propose that HSP90 and Sgt1p act together as a molecular switch, maintaining transient interactions required to balance protein complex assembly with turnover.


2010 ◽  
Vol 56 (10) ◽  
pp. 1535-1543 ◽  
Author(s):  
Jing-Ping Lin ◽  
Libor Vitek ◽  
Harvey A Schwertner

BACKGROUND Serum bilirubin has been consistently shown to be inversely related to cardiovascular disease (CVD). Recent studies showed serum bilirubin to be associated with CVD-related factors such as diabetes, metabolic syndrome, and body mass index. Although the association of serum bilirubin with CVD has been found in both retrospective and prospective studies, less information is available on the role of genes that control bilirubin concentrations and their association with CVD. CONTENT In this review, we provide detailed information on the identity of the major genes that control bilirubin concentrations and their association with serum bilirubin concentrations and CVD risk. We also update the results of the major studies that have been performed on the association between serum bilirubin, CVD, and CVD-related diseases such as diabetes or metabolic syndrome. Studies consistently indicate that bilirubin concentrations are inversely associated with different types of CVD and CVD-related diseases. A conditional linkage study indicates that UGT1A1 is the major gene controlling serum bilirubin concentrations, and this finding has been confirmed in recent genomewide association studies. Studies also indicate that individuals homozygous for UGT1A1*28 have a significantly lower risk of developing CVD than carriers of the wild-type alleles. SUMMARY Serum bilirubin has a protective effect on CVD and CVD-related diseases, and UGT1A1 is the major gene controlling serum bilirubin concentrations. Pharmacologic, nonpharmacologic, or genetic interventions that increase serum bilirubin concentrations could provide more direct evidence on the role of bilirubin in CVD prevention.


2017 ◽  
pp. 38-48
Author(s):  
Henry Sutanto

Cardiovascular disease is one of the deadliest diseases in the world. Nowadays, alongside the developments of various medical therapeutic strategies, there is a decreasing trend of cardiovascular mortality. However, this reduction is not adequate and needs to be supported by cardiovascular prevention approaches. Statins and aspirin are two of cardiovascular drugs that are believed to be beneficial in cardiovascular prevention. Their magnificent efficacies in the secondary prevention setting lead them to be used in the primary prevention. However, some safety issues associated with the drugs should be considered. For that reason, based on previous trials and studies, some recommendations regarding the efficacy-safety issues are developed.


2019 ◽  
Vol 41 (6) ◽  
pp. 772-782 ◽  
Author(s):  
Michael T Osborne ◽  
Azar Radfar ◽  
Malek Z O Hassan ◽  
Shady Abohashem ◽  
Blake Oberfeld ◽  
...  

Abstract Aims Chronic noise exposure associates with increased cardiovascular disease (CVD) risk; however, the role of confounders and the underlying mechanism remain incompletely defined. The amygdala, a limbic centre involved in stress perception, participates in the response to noise. Higher amygdalar metabolic activity (AmygA) associates with increased CVD risk through a mechanism involving heightened arterial inflammation (ArtI). Accordingly, in this retrospective study, we tested whether greater noise exposure associates with higher: (i) AmygA, (ii) ArtI, and (iii) risk for major adverse cardiovascular disease events (MACE). Methods and results Adults (N = 498) without CVD or active cancer underwent clinical 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging. Amygdalar metabolic activity and ArtI were measured, and MACE within 5 years was adjudicated. Average 24-h transportation noise and potential confounders were estimated at each individual’s home address. Over a median 4.06 years, 40 individuals experienced MACE. Higher noise exposure (per 5 dBA increase) predicted MACE [hazard ratio (95% confidence interval, CI) 1.341 (1.147–1.567), P < 0.001] and remained robust to multivariable adjustments. Higher noise exposure associated with increased AmygA [standardized β (95% CI) 0.112 (0.051–0.174), P < 0.001] and ArtI [0.045 (0.001–0.090), P = 0.047]. Mediation analysis suggested that higher noise exposure associates with MACE via a serial mechanism involving heightened AmygA and ArtI that accounts for 12–26% of this relationship. Conclusion Our findings suggest that noise exposure associates with MACE via a mechanism that begins with increased stress-associated limbic (amygdalar) activity and includes heightened arterial inflammation. This potential neurobiological mechanism linking noise to CVD merits further evaluation in a prospective population.


2018 ◽  
Vol 24 (3) ◽  
pp. 281-290 ◽  
Author(s):  
Peter Riis Hansen

Inflammation plays a significant role in atherosclerosis and cardiovascular disease (CVD). Patients with chronic inflammatory diseases are at increased risk of CVD, but it is debated whether this association is causal or dependent on shared risk factors, other exposures, genes, and/or inflammatory pathways. The current review summarizes epidemiological, clinical, and experimental data supporting the role of shared inflammatory mechanisms between atherosclerotic CVD and rheumatoid arthritis, psoriasis, inflammatory bowel disease, and periodontitis, respectively, and provides insights to future prospects in this area of research. Awareness of the role of inflammation in CVD in patients with chronic inflammatory diseases and the potential for anti-inflammatory therapy, e.g., with tumor necrosis factor-α inhibitors, to also reduce atherosclerotic CVD has evolved into guideline- based recommendations. These include regular CVD risk assessment, aggressive treatment of traditional CVD risk factors, and recognition of reduced CVD as an added benefit of strict inflammatory disease control. At present, chronic inflammatory diseases would appear to qualify as partners in crime and not merely innocent bystanders to CVD. However, definite incremental contributions of inflammation versus effects of the complex interplay with other CVD risk factors may never be fully elucidated and for the foreseeable future, inflammation is posed to maintain its current position as both a marker and a maker of CVD, with clinical utility both for identification of patient at risk of CVD and as target for therapy to reduce CVD.


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