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      The Pivotal Role of Oxidative Stress in the Pathophysiology of Cardiovascular-Renal Remodeling in Kidney Disease

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          Abstract

          The excessive activation of the renin-angiotensin system in kidney disease leads to alteration of intracellular pathways which concur altogether to the induction of cardiovascular and renal remodeling, exposing these patients since the very beginning of the renal injury to chronic kidney disease and progression to end stage renal disease, a very harmful and life threatening clinical condition. Oxidative stress plays a pivotal role in the pathophysiology of renal injury and cardiovascular-renal remodeling, the long-term consequence of its effect. This review will examine the role of oxidative stress in the most significant pathways involved in cardiovascular and renal remodeling with a focus on the detrimental effects of oxidative stress-mediated renal abnormalities on the progression of the disease and of its complications. Food for thoughts on possible therapeutic target are proposed on the basis of experimental evidences.

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          Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal

          Antonio Ayala, Mario F Muñoz, Sandro Argüelles (2014)
          Lipid peroxidation can be described generally as a process under which oxidants such as free radicals attack lipids containing carbon-carbon double bond(s), especially polyunsaturated fatty acids (PUFAs). Over the last four decades, an extensive body of literature regarding lipid peroxidation has shown its important role in cell biology and human health. Since the early 1970s, the total published research articles on the topic of lipid peroxidation was 98 (1970–1974) and has been increasing at almost 135-fold, by up to 13165 in last 4 years (2010–2013). New discoveries about the involvement in cellular physiology and pathology, as well as the control of lipid peroxidation, continue to emerge every day. Given the enormity of this field, this review focuses on biochemical concepts of lipid peroxidation, production, metabolism, and signaling mechanisms of two main omega-6 fatty acids lipid peroxidation products: malondialdehyde (MDA) and, in particular, 4-hydroxy-2-nonenal (4-HNE), summarizing not only its physiological and protective function as signaling molecule stimulating gene expression and cell survival, but also its cytotoxic role inhibiting gene expression and promoting cell death. Finally, overviews of in vivo mammalian model systems used to study the lipid peroxidation process, and common pathological processes linked to MDA and 4-HNE are shown.
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            Role of ROS and RNS Sources in Physiological and Pathological Conditions

            Sergio Di Meo, Tanea T. Reed, Paola Venditti … (2016)
            There is significant evidence that, in living systems, free radicals and other reactive oxygen and nitrogen species play a double role, because they can cause oxidative damage and tissue dysfunction and serve as molecular signals activating stress responses that are beneficial to the organism. Mitochondria have been thought to both play a major role in tissue oxidative damage and dysfunction and provide protection against excessive tissue dysfunction through several mechanisms, including stimulation of opening of permeability transition pores. Until recently, the functional significance of ROS sources different from mitochondria has received lesser attention. However, the most recent data, besides confirming the mitochondrial role in tissue oxidative stress and protection, show interplay between mitochondria and other ROS cellular sources, so that activation of one can lead to activation of other sources. Thus, it is currently accepted that in various conditions all cellular sources of ROS provide significant contribution to processes that oxidatively damage tissues and assure their survival, through mechanisms such as autophagy and apoptosis.
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              Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology

              Steven J. Forrester, George Booz, Curt Sigmund … (2018)
              The renin-angiotensin-aldosterone system plays crucial roles in cardiovascular physiology and pathophysiology. However, many of the signaling mechanisms have been unclear. The angiotensin II (ANG II) type 1 receptor (AT 1 R) is believed to mediate most functions of ANG II in the system. AT 1 R utilizes various signal transduction cascades causing hypertension, cardiovascular remodeling, and end organ damage. Moreover, functional cross-talk between AT 1 R signaling pathways and other signaling pathways have been recognized. Accumulating evidence reveals the complexity of ANG II signal transduction in pathophysiology of the vasculature, heart, kidney, and brain, as well as several pathophysiological features, including inflammation, metabolic dysfunction, and aging. In this review, we provide a comprehensive update of the ANG II receptor signaling events and their functional significances for potential translation into therapeutic strategies. AT 1 R remains central to the system in mediating physiological and pathophysiological functions of ANG II, and participation of specific signaling pathways becomes much clearer. There are still certain limitations and many controversies, and several noteworthy new concepts require further support. However, it is expected that rigorous translational research of the ANG II signaling pathways including those in large animals and humans will contribute to establishing effective new therapies against various diseases.
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                Author and article information

                Contributors
                Munehiro Kitada: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): Antioxidants (Basel)
                Journal ID (iso-abbrev): Antioxidants (Basel)
                Journal ID (publisher-id): antioxidants
                Title: Antioxidants
                Publisher: MDPI
                ISSN (Electronic): 2076-3921
                Publication date (Electronic): 29 June 2021
                Publication date Collection: July 2021
                Volume: 10
                Issue: 7
                Electronic Location Identifier: 1041
                Affiliations
                Nephrology, Dialysis and Transplantation Unit, Department of Medicine, University of Padova, 35128 Padova, Italy; verdiana.ravarotto@ 123456gmail.com (V.R.); giovanni.bertoldi@ 123456studenti.unipd.it (G.B.); georgie.innico@ 123456unipd.it (G.I.); laura.gobbi_01@ 123456aopd.veneto.it (L.G.)
                Author notes
                [* ]Correspondence: renzcalo@ 123456unipd.it ; Tel.: +39-049-8213071
                Author information
                https://orcid.org/0000-0001-6498-6671
                https://orcid.org/0000-0002-7534-0128
                Article
                Publisher ID: antioxidants-10-01041
                DOI: 10.3390/antiox10071041
                PMC ID: 8300817
                PubMed ID: 34209494
                SO-VID: 8ddac945-51cd-4a94-b6b2-d86b6f721d75
                Copyright © © 2021 by the authors.
                License:

                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 ( https://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 07 June 2021
                Date accepted : 28 June 2021
                Categories
                Subject: Review

                Keywords: oxidative stress,renin-angiotensin system,cardiovascular disease,chronic kidney disease,dialysis
                Data availability:
                Keywords: oxidative stress, renin-angiotensin system, cardiovascular disease, chronic kidney disease, dialysis

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