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      Oxidative Stress and Inflammation in Cardiovascular Diseases

      editorial
      Antioxidants
      MDPI

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          Abstract

          Cardiovascular diseases (CVD), which include a number of cardiac and vascular conditions, resulted in approximately 17.8 million deaths in 2017 [1]. Oxidative stress and inflammation are intricately linked mechanisms and are significant drivers in the development and progression of cardiovascular disease. In this Special Issue, the authors demonstrate the number of organs and processes affected in cardiovascular diseases. This is conclusively demonstrated in an extensive and detailed review undertaken by Podkowinska and Formanowicz that encompasses ROS, inflammation and CVD in chronic kidney disease (CKD). This review examined how oxidative stress and inflammation lead to the progression of CKD to end-stage renal disease (ESRD) and how complications of CKD accelerate CVD [2]. Another review by Ryze et al. focused on the risk of CVD in ESRD patients requiring dialysis, a process which enhances oxidative stress [3]. Together, these articles provide a great in-depth analysis of the field to date. The original research published in this Special Issue focused on specific aspects of CVD that are just as diverse as the contents of the reviews mentioned above. The renin–angiotensin–aldosterone system is important in regulating blood pressure (BP), where dysregulation can not only lead to aberrations in BP but also increased ROS and inflammation. Aryal et al. showed that the intrarenal AngII activation and subsequent induction of ROS could be mechanistically responsible for increased BP during chronic metabolic acidosis [4]. In another article, the treatment of heart failure in rats was considered by Pop et al., where alpha-lipoic acid was shown to have protective effects on the cardiovascular system through preventing body weight gain and by decreasing metabolic and cardiac perturbations [5]. Arellano-Buendia et al. were interested in oxidative stress in vascular complications and ESRD, since many patients, despite taking the current treatments for diabetic nephropathy, progress to ESRD [6]. Here, they looked at the ability of allicin to delay the progression of diabetic nephropathy and found that allicin had antioxidant, antifibrotic and antidiabetic properties. Other antioxidants from waste material generated from Crocus sativus petals were examined by Zeka et al. for their effects on the cardiovascular system. Crocin and kaempferol from saffron petal extract were shown to increase cell viability and decrease intracellular ROS formation [7]. Methylglyoxal (MGO), a reactive glucose metabolite that generates ROS and cellular damage, has been implicated in cardiovascular diseases. Do et al. tested 20 different compounds extracted from Peucedanum japonicum roots and determined their ability to prevent MGO-mediated endothelial dysfunction [8]. Here, they showed that isosamidin was able to prevent MGO-induced ROS and apoptotic signalling in endothelial cells and therefore suggested that isosamidin may protect against endothelial dysfunction. Others looked at CVD in patients. Firstly, Ismaeel et al. examined the role of biopterins and oxidative stress in peripheral artery disease (PAD), where they tested molecules involved in nitric oxide (NO) bioavailability [9]. Here, they found that NO bioavailability is reduced in patients with PAD which may be caused by increased oxidative stress and reductions in tetrahydrobiopterin (BH4) [9]. Interesting data are reported by Rodriguez-Sanchez et al., where they studied the cardiovascular risk (CVR) in young subjects with or without stable coronary artery disease (SCAD) by examining the association of oxLDL and NT-proBNP. Here, they demonstrated that these markers were significantly higher in individuals with high CVR and lower in individuals with SCAD [10]. I would like to acknowledge the authors that have contributed to the Special Issue “Oxidative Stress and Inflammation in Cardiovascular Diseases”. This Special Issue has highlighted the need for further research into the mechanisms involved in CVD as well as the need for the development of novel therapeutics to treat the broad range of illnesses under the umbrella of CVD.

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          Most cited references10

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          Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the Global Burden of Disease Study 2017

          Summary Background Global development goals increasingly rely on country-specific estimates for benchmarking a nation's progress. To meet this need, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 estimated global, regional, national, and, for selected locations, subnational cause-specific mortality beginning in the year 1980. Here we report an update to that study, making use of newly available data and improved methods. GBD 2017 provides a comprehensive assessment of cause-specific mortality for 282 causes in 195 countries and territories from 1980 to 2017. Methods The causes of death database is composed of vital registration (VR), verbal autopsy (VA), registry, survey, police, and surveillance data. GBD 2017 added ten VA studies, 127 country-years of VR data, 502 cancer-registry country-years, and an additional surveillance country-year. Expansions of the GBD cause of death hierarchy resulted in 18 additional causes estimated for GBD 2017. Newly available data led to subnational estimates for five additional countries—Ethiopia, Iran, New Zealand, Norway, and Russia. Deaths assigned International Classification of Diseases (ICD) codes for non-specific, implausible, or intermediate causes of death were reassigned to underlying causes by redistribution algorithms that were incorporated into uncertainty estimation. We used statistical modelling tools developed for GBD, including the Cause of Death Ensemble model (CODEm), to generate cause fractions and cause-specific death rates for each location, year, age, and sex. Instead of using UN estimates as in previous versions, GBD 2017 independently estimated population size and fertility rate for all locations. Years of life lost (YLLs) were then calculated as the sum of each death multiplied by the standard life expectancy at each age. All rates reported here are age-standardised. Findings At the broadest grouping of causes of death (Level 1), non-communicable diseases (NCDs) comprised the greatest fraction of deaths, contributing to 73·4% (95% uncertainty interval [UI] 72·5–74·1) of total deaths in 2017, while communicable, maternal, neonatal, and nutritional (CMNN) causes accounted for 18·6% (17·9–19·6), and injuries 8·0% (7·7–8·2). Total numbers of deaths from NCD causes increased from 2007 to 2017 by 22·7% (21·5–23·9), representing an additional 7·61 million (7·20–8·01) deaths estimated in 2017 versus 2007. The death rate from NCDs decreased globally by 7·9% (7·0–8·8). The number of deaths for CMNN causes decreased by 22·2% (20·0–24·0) and the death rate by 31·8% (30·1–33·3). Total deaths from injuries increased by 2·3% (0·5–4·0) between 2007 and 2017, and the death rate from injuries decreased by 13·7% (12·2–15·1) to 57·9 deaths (55·9–59·2) per 100 000 in 2017. Deaths from substance use disorders also increased, rising from 284 000 deaths (268 000–289 000) globally in 2007 to 352 000 (334 000–363 000) in 2017. Between 2007 and 2017, total deaths from conflict and terrorism increased by 118·0% (88·8–148·6). A greater reduction in total deaths and death rates was observed for some CMNN causes among children younger than 5 years than for older adults, such as a 36·4% (32·2–40·6) reduction in deaths from lower respiratory infections for children younger than 5 years compared with a 33·6% (31·2–36·1) increase in adults older than 70 years. Globally, the number of deaths was greater for men than for women at most ages in 2017, except at ages older than 85 years. Trends in global YLLs reflect an epidemiological transition, with decreases in total YLLs from enteric infections, respiratory infections and tuberculosis, and maternal and neonatal disorders between 1990 and 2017; these were generally greater in magnitude at the lowest levels of the Socio-demographic Index (SDI). At the same time, there were large increases in YLLs from neoplasms and cardiovascular diseases. YLL rates decreased across the five leading Level 2 causes in all SDI quintiles. The leading causes of YLLs in 1990—neonatal disorders, lower respiratory infections, and diarrhoeal diseases—were ranked second, fourth, and fifth, in 2017. Meanwhile, estimated YLLs increased for ischaemic heart disease (ranked first in 2017) and stroke (ranked third), even though YLL rates decreased. Population growth contributed to increased total deaths across the 20 leading Level 2 causes of mortality between 2007 and 2017. Decreases in the cause-specific mortality rate reduced the effect of population growth for all but three causes: substance use disorders, neurological disorders, and skin and subcutaneous diseases. Interpretation Improvements in global health have been unevenly distributed among populations. Deaths due to injuries, substance use disorders, armed conflict and terrorism, neoplasms, and cardiovascular disease are expanding threats to global health. For causes of death such as lower respiratory and enteric infections, more rapid progress occurred for children than for the oldest adults, and there is continuing disparity in mortality rates by sex across age groups. Reductions in the death rate of some common diseases are themselves slowing or have ceased, primarily for NCDs, and the death rate for selected causes has increased in the past decade. Funding Bill & Melinda Gates Foundation.
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            Chronic Kidney Disease as Oxidative Stress- and Inflammatory-Mediated Cardiovascular Disease

            Generating reactive oxygen species (ROS) is necessary for both physiology and pathology. An imbalance between endogenous oxidants and antioxidants causes oxidative stress, contributing to vascular dysfunction. The ROS-induced activation of transcription factors and proinflammatory genes increases inflammation. This phenomenon is of crucial importance in patients with chronic kidney disease (CKD), because atherosclerosis is one of the critical factors of their cardiovascular disease (CVD) and increased mortality. The effect of ROS disrupts the excretory function of each section of the nephron. It prevents the maintenance of intra-systemic homeostasis and leads to the accumulation of metabolic products. Renal regulatory mechanisms, such as tubular glomerular feedback, myogenic reflex in the supplying arteriole, and the renin–angiotensin–aldosterone system, are also affected. It makes it impossible for the kidney to compensate for water–electrolyte and acid–base disturbances, which progress further in the mechanism of positive feedback, leading to a further intensification of oxidative stress. As a result, the progression of CKD is observed, with a spectrum of complications such as malnutrition, calcium phosphate abnormalities, atherosclerosis, and anemia. This review aimed to show the role of oxidative stress and inflammation in renal impairment, with a particular emphasis on its influence on the most common disturbances that accompany CKD.
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              Effects of Allicin on Pathophysiological Mechanisms during the Progression of Nephropathy Associated to Diabetes

              This study aimed to assess the impact of allicin on the course of diabetic nephropathy. Study groups included control, diabetes, and diabetes-treated rats. Allicin treatment (16 mg/kg day/p.o.) started after 1 month of diabetes onset and was administered for 30 days. In the diabetes group, the systolic blood pressure (SBP) increased, also, the oxidative stress and hypoxia in the kidney cortex were evidenced by alterations in the total antioxidant capacity as well as the expression of nuclear factor (erythroid-derived 2)-like 2/Kelch ECH associating protein 1 (Nrf2/Keap1), hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), erythropoietin (Epo) and its receptor (Epo-R). Moreover, diabetes increased nephrin, and kidney injury molecule-1 (KIM-1) expression that correlated with mesangial matrix, the fibrosis index and with the expression of connective tissue growth factor (CTGF), transforming growth factor-β1 (TGF-β1), and α-smooth muscle actin (α-SMA). The insulin levels and glucose transporter protein type-4 (GLUT4) expression were decreased; otherwise, insulin receptor substrates 1 and 2 (IRS-1 and IRS-2) expression was increased. Allicin increased Nrf2 expression and decreased SBP, Keap1, HIF-1α, and VEGF expression. Concurrently, nephrin, KIM-1, the mesangial matrix, fibrosis index, and the fibrotic proteins were decreased. Additionally, allicin decreased hyperglycemia, improved insulin levels, and prevented changes in (GLUT4) and IRSs expression induced by diabetes. In conclusion, our results demonstrate that allicin has the potential to help in the treatment of diabetic nephropathy. The cellular mechanisms underlying its effects mainly rely on the regulation of antioxidant, antifibrotic, and antidiabetic mechanisms, which can contribute towards delay in the progression of renal disease.
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                Author and article information

                Journal
                Antioxidants (Basel)
                Antioxidants (Basel)
                antioxidants
                Antioxidants
                MDPI
                2076-3921
                25 January 2021
                February 2021
                : 10
                : 2
                : 171
                Affiliations
                Department of Diabetes, Central Clinical School, Monash University, Melbourne, VIC 3800, Australia; Raelene.Pickering@ 123456monash.edu
                Article
                antioxidants-10-00171
                10.3390/antiox10020171
                7912407
                33503818
                012dcf5d-e453-4bf8-8fa7-a70686b10c85
                © 2021 by the author.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 20 January 2021
                : 21 January 2021
                Categories
                Editorial

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