scholarly journals Perspectives of incretin mimetics in cardiovascular diseases

2021 ◽  
Vol 20 (1) ◽  
pp. 55-62
Author(s):  
João Felipe R. Cardoso ◽  
Célia Cohen ◽  
Fernanda J. Medeiros ◽  
Fabiano M. Serfaty ◽  
Mario F. T. Neves

Introduction: Type 2 Diabetes (DM2) is a chronic conditionassociated with an increased risk of cardiovascular diseases,neuropathies, nephropathies and eye diseases. Incretins (GIPand GLP-1) are hormones important to insulin secretion, andtheir actions are compromised in DM2 patients. Objectives:This review considers the opportunities and challenges ofusing incretin mimetics in the treatment of DM2. Methods:Bibliographic review referring to the period from 2000 to2020, in electronic databases such as Scielo, Lilacs, PubMed,Web of Science. Results: Incretins stimulate insulin secretionby the pancreas in response to nutrient intake, with a lowerpotential to cause hypoglycemia. In addition, they have acardioprotective role, reducing blood pressure, improvingendothelial and myocardial function, and their use has beenassociated with a reduction in the risk of cardiovascularevents, including cardiovascular mortality. Clinical trialswith GLP-1R agonists (GLP-1RA) reduced albuminuria, increasednatriuresis, and decreased oxidative stress. In addition,treatment with incretin mimetics reduced the occurrence ofthe main cardiovascular outcomes related to atherosclerosis,promoted weight loss and improved lipid profile. Conclusion:Studies show the important role of incretin mimetics in thepathophysiology and treatment of DM2, with significanteffects in the cardiovascular system. However, its use must beevaluated in relation to its safety and to in which individualsthe benefits outweigh the risks associated with the treatment.Thus, its clinical relevance depends on studies with long-termfollow-up of patients, with analysis of its impact on mortalityand on the development of micro and macrovascularcomplications.

Pathologia ◽  
2021 ◽  
Vol 18 (2) ◽  
pp. 229-242
Author(s):  
M. P. Kopytsia ◽  
Yu. V. Rodionova ◽  
N. V. Tytarenko ◽  
I. M. Kutia ◽  
Ya. V. Нilоva

Myeloperoxidase is one of the key enzymes involved in oxidative stress and inflammation. Its elevated levels are determined in a wide range of both acute and chronic forms of cardiovascular diseases. The inflammation results in the release of the enzyme from the white blood cells to form products such as hypochlorous acid, which in turn can have a negative effect on the target proteins. Inconsistent evidence on the predictive role of this biomarker in diseases of the circulatory system generates scientific interest and provokes further research in this direction. The aim of this review is to analyze the scientific literature data on myeloperoxidase as a possible clinical use for the diagnosis and risk stratification of patients with саrdiovascular diseases. Materials and methods. Searching and generalization of data from leading specialized sources, which are indexed by scientific databases PubMed, SCOPUS, Web of Science. Results. The results of the studies indicate that myeloperoxidase is actively involved in the pathophysiology of cardiovascular diseases through participation in oxidative stress and inflammation, excessive production of proatherogenic lipoproteins, changes in nitric oxide activity, endothelial dysfunction, and due to the effect on the instability of atherosclerotic plaques. In patients with cardiovascular diseases, including ischemic heart disease, the concentration of the indicated protein is increased and is often associated with a poor prognosis, including an increased risk of mortality. Myeloperoxidase metabolites are often the factors that contribute to cell damage under conditions of ischemia. The review also considers the relationship of the enzyme with the development of restenosis and the effectiveness of revascularization after percutaneous coronary intervention. Conclusions. The presented data mainly define myeloperoxidase as a significant marker for predicting long-term follow-up results and the development of serious adverse cardiovascular events, mortality in patients with cardiovascular disease. At the same time, despite the great achievements in disclosing the complex effects of myeloperoxidase, inconsistency in the available results is noteworthy. This controversy necessitates further research to elucidate and reveal the full clinical potential of myeloperoxidase in patients with cardiovascular pathology.


2016 ◽  
Vol 22 (18) ◽  
pp. 2650-2656 ◽  
Author(s):  
Noelia Diaz-Morales ◽  
Susana Rovira-Llopis ◽  
Irene Escribano-Lopez ◽  
Celia Bañuls ◽  
Sandra Lopez-Domenech ◽  
...  

2018 ◽  
Vol 15 (1) ◽  
pp. 31-43 ◽  
Author(s):  
Sayantan Nath ◽  
Sambuddha Das ◽  
Aditi Bhowmik ◽  
Sankar Kumar Ghosh ◽  
Yashmin Choudhury

Background:Studies pertaining to association of GSTM1 and GSTT1 null genotypes with risk of T2DM and its complications were often inconclusive, thus spurring the present study.Methods:Meta-analysis of 25 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in determining the risk for T2DM and 17 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in development of T2DM related complications were conducted.Results:Our study revealed an association between GSTM1 and GSTT1 null polymorphism with T2DM (GSTM1; OR=1.37;95% CI =1.10-1.70 and GSTT1; OR=1.29;95% CI =1.04-1.61) with an amplified risk of 2.02 fold for combined GSTM1-GSTT1 null genotypes. Furthermore, the GSTT1 null (OR=1.56;95%CI=1.38-1.77) and combined GSTM1-GSTT1 null genotypes (OR=1.91;95%CI=1.25- 2.94) increased the risk for development of T2DM related complications, but not the GSTM1 null genotype. Stratified analyses based on ethnicity revealed GSTM1 and GSTT1 null genotypes increase the risk for T2DM in both Caucasians and Asians, with Asians showing much higher risk of T2DM complications than Caucasians for the same. </P><P> Discussion: GSTM1, GSTT1 and combined GSTM1-GSTT1 null polymorphism may be associated with increased risk for T2DM; while GSTT1 and combined GSTM1-GSTT1 null polymorphism may increase the risk of subsequent development of T2DM complications with Asian population carrying an amplified risk for the polymorphism.Conclusion:Thus GSTM1 and GSTT1 null genotypes increases the risk for Type 2 diabetes mellitus alone, in combination or with regards to ethnicity.


2020 ◽  
Vol 16 ◽  
Author(s):  
Patricio Lopez-Jaramillo ◽  
Jose Lopez-Lopez ◽  
Daniel Cohen ◽  
Natalia Alarcon-Ariza ◽  
Margarita Mogollon-Zehr

: Hypertension and type 2 diabetes mellitus are two important risk factors that contribute to cardiovascular diseases worldwide. In Latin America hypertension prevalence varies from 30 to 50%. Moreover, the proportion of awareness, treatment and control of hypertension is very low. The prevalence of type 2 diabetes mellitus varies from 8 to 13% and near to 40% are unaware of their condition. In addition, the prevalence of prediabetes varies from 6 to 14% and this condition has been also associated with increased risk of cardiovascular diseases. The principal factors linked to a higher risk of hypertension in Latin America are increased adiposity, low muscle strength, unhealthy diet, low physical activity and low education. Besides being chronic conditions, leading causes of cardiovascular mortality, both hypertension and type 2 diabetes mellitus represent a substantial cost for the weak health systems of Latin American countries. Therefore, is necessary to implement and reinforce public health programs to improve awareness, treatment and control of hypertension and type 2 diabetes mellitus, in order to reach the mandate of the Unit Nations of decrease the premature mortality for CVD.


Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 629
Author(s):  
Jorge Gutiérrez-Cuevas ◽  
Ana Sandoval-Rodriguez ◽  
Alejandra Meza-Rios ◽  
Hugo Christian Monroy-Ramírez ◽  
Marina Galicia-Moreno ◽  
...  

Obesity is defined as excessive body fat accumulation, and worldwide obesity has nearly tripled since 1975. Excess of free fatty acids (FFAs) and triglycerides in obese individuals promote ectopic lipid accumulation in the liver, skeletal muscle tissue, and heart, among others, inducing insulin resistance, hypertension, metabolic syndrome, type 2 diabetes (T2D), atherosclerosis, and cardiovascular disease (CVD). These diseases are promoted by visceral white adipocyte tissue (WAT) dysfunction through an increase in pro-inflammatory adipokines, oxidative stress, activation of the renin-angiotensin-aldosterone system (RAAS), and adverse changes in the gut microbiome. In the heart, obesity and T2D induce changes in substrate utilization, tissue metabolism, oxidative stress, and inflammation, leading to myocardial fibrosis and ultimately cardiac dysfunction. Peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of carbohydrate and lipid metabolism, also improve insulin sensitivity, triglyceride levels, inflammation, and oxidative stress. The purpose of this review is to provide an update on the molecular mechanisms involved in obesity-linked CVD pathophysiology, considering pro-inflammatory cytokines, adipokines, and hormones, as well as the role of oxidative stress, inflammation, and PPARs. In addition, cell lines and animal models, biomarkers, gut microbiota dysbiosis, epigenetic modifications, and current therapeutic treatments in CVD associated with obesity are outlined in this paper.


Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 377
Author(s):  
Yunna Lee ◽  
Eunok Im

Cardiovascular diseases (CVDs) are the most common cause of morbidity and mortality worldwide. The potential benefits of natural antioxidants derived from supplemental nutrients against CVDs are well known. Remarkably, natural antioxidants exert cardioprotective effects by reducing oxidative stress, increasing vasodilation, and normalizing endothelial dysfunction. Recently, considerable evidence has highlighted an important role played by the synergistic interaction between endothelial nitric oxide synthase (eNOS) and sirtuin 1 (SIRT1) in the maintenance of endothelial function. To provide a new perspective on the role of natural antioxidants against CVDs, we focused on microRNAs (miRNAs), which are important posttranscriptional modulators in human diseases. Several miRNAs are regulated via the consumption of natural antioxidants and are related to the regulation of oxidative stress by targeting eNOS and/or SIRT1. In this review, we have discussed the specific molecular regulation of eNOS/SIRT1-related endothelial dysfunction and its contribution to CVD pathologies; furthermore, we selected nine different miRNAs that target the expression of eNOS and SIRT1 in CVDs. Additionally, we have summarized the alteration of miRNA expression and regulation of activities of miRNA through natural antioxidant consumption.


2017 ◽  
Vol 49 (5S) ◽  
pp. 451
Author(s):  
Pegah Akbari ◽  
Naoto Fujii ◽  
Sheila Dervis ◽  
Robert D. Meade ◽  
Pierre Boulay ◽  
...  

2005 ◽  
Vol 10 (1_suppl) ◽  
pp. S45-S48 ◽  
Author(s):  
Veli-Pekka Valkonen ◽  
Tomi-Pekka Tuomainen ◽  
Reijo Laaksonen

The crucial role of nitric oxide (NO) for normal endothelial function is well known. In many conditions associated with increased risk of cardiovascular diseases such as hypercholesterolemia, hypertension, abdominal obesity, diabetes and smok ing, NO biosynthesis is dysregulated, leading to endothelial dysfunction. The grow ing evidence from animal and human studies indicates that endogenous inhibitors of endothelial NO synthase such as asymmetric dimethylarginine (ADMA) and NG-monomethyl-L-arginine (L-NMMA) are associated with the endothelial dysfunc tion and potentially regulate NO synthase. The major route of elimination of ADMA is metabolism by the enzymes dimethylarginine dimethylaminohydrolase-1 and -2 (DDAH). In our recent study 16 men with either low or high plasma ADMA concen trations were screened to identify DDAH polymorphisms that could potentially be associated with increased susceptibility to cardiovascular diseases. In that study a novel functional mutation of DDAH-1 was identified; the mutation carriers had a significantly elevated risk for cardiovascular disease and a tendency to develop hypertension. These results confirmed the clinical role of DDAH enzymes in ADMA metabolism. Furthermore, it is possible that more common variants of DDAH genes contribute more widely to increased cardiovascular risk.


Author(s):  
Siphosethu Cassandra Maphumulo ◽  
Etheresia Pretorius

AbstractType 2 diabetes mellitus (T2DM) is a multifactorial chronic metabolic disease characterized by chronic hyperglycemia due to insulin resistance and a deficiency in insulin secretion. The global diabetes pandemic relates primarily to T2DM, which is the most prevalent form of diabetes, accounting for over 90% of all cases. Chronic low-grade inflammation, triggered by numerous risk factors, and the chronic activation of the immune system are prominent features of T2DM. Here we highlight the role of blood cells (platelets, and red and white blood cells) and vascular endothelial cells as drivers of systemic inflammation in T2DM. In addition, we discuss the role of microparticles (MPs) in systemic inflammation and hypercoagulation. Although once seen as inert by-products of cell activation or destruction, MPs are now considered to be a disseminated storage pool of bioactive effectors of thrombosis, inflammation, and vascular function. They have been identified to circulate at elevated levels in the bloodstream of individuals with increased risk of atherothrombosis or cardiovascular disease, two significant hallmark conditions of T2DM. There is also general evidence that MPs activate blood cells, express proinflammatory and coagulant effects, interact directly with cell receptors, and transfer biological material. MPs are considered major players in the pathogenesis of many systemic inflammatory diseases and may be potentially useful biomarkers of disease activity and may not only be of prognostic value but may act as novel therapeutic targets.


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