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      A Review of Cardiovascular Toxicity of Microcystins

      review-article
      , , , *
      Toxins
      MDPI
      microcystins (MCs), toxicity, cardiovascular disease (CVD)

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          Abstract

          The mortality rate of cardiovascular diseases (CVD) in China is on the rise. The increasing burden of CVD in China has become a major public health problem. Cyanobacterial blooms have been recently considered a global environmental concern. Microcystins (MCs) are the secondary products of cyanobacteria metabolism and the most harmful cyanotoxin found in water bodies. Recent studies provide strong evidence of positive associations between MC exposure and cardiotoxicity, representing a threat to human cardiovascular health. This review focuses on the effects of MCs on the cardiovascular system and provides some evidence that CVD could be induced by MCs. We summarized the current knowledge of the cardiovascular toxicity of MCs, with regard to direct cardiovascular toxicity and indirect cardiovascular toxicity. Toxicity of MCs is mainly governed by the increasing level of reactive oxygen species (ROS), oxidative stress in mitochondria and endoplasmic reticulum, the inhibition activities of serine/threonine protein phosphatase 1 (PP1) and 2A (PP2A) and the destruction of cytoskeletons, which finally induce the occurrence of CVD. To protect human health from the threat of MCs, this paper also puts forward some directions for further research.

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          Most cited references142

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          Regulation of endothelial permeability via paracellular and transcellular transport pathways.

          The endothelium functions as a semipermeable barrier regulating tissue fluid homeostasis and transmigration of leukocytes and providing essential nutrients across the vessel wall. Transport of plasma proteins and solutes across the endothelium involves two different routes: one transcellular, via caveolae-mediated vesicular transport, and the other paracellular, through interendothelial junctions. The permeability of the endothelial barrier is an exquisitely regulated process in the resting state and in response to extracellular stimuli and mediators. The focus of this review is to provide a comprehensive overview of molecular and signaling mechanisms regulating endothelial barrier permeability with emphasis on the cross-talk between paracellular and transcellular transport pathways.
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            Cyanobacterial toxins: risk management for health protection.

            This paper reviews the occurrence and properties of cyanobacterial toxins, with reference to the recognition and management of the human health risks which they may present. Mass populations of toxin-producing cyanobacteria in natural and controlled waterbodies include blooms and scums of planktonic species, and mats and biofilms of benthic species. Toxic cyanobacterial populations have been reported in freshwaters in over 45 countries, and in numerous brackish, coastal, and marine environments. The principal toxigenic genera are listed. Known sources of the families of cyanobacterial toxins (hepato-, neuro-, and cytotoxins, irritants, and gastrointestinal toxins) are briefly discussed. Key procedures in the risk management of cyanobacterial toxins and cells are reviewed, including derivations (where sufficient data are available) of tolerable daily intakes (TDIs) and guideline values (GVs) with reference to the toxins in drinking water, and guideline levels for toxigenic cyanobacteria in bathing waters. Uncertainties and some gaps in knowledge are also discussed, including the importance of exposure media (animal and plant foods), in addition to potable and recreational waters. Finally, we present an outline of steps to develop and implement risk management strategies for cyanobacterial cells and toxins in waterbodies, with recent applications and the integration of Hazard Assessment Critical Control Point (HACCP) principles.
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              Prolonged endoplasmic reticulum stress in hypertrophic and failing heart after aortic constriction: possible contribution of endoplasmic reticulum stress to cardiac myocyte apoptosis.

              The endoplasmic reticulum (ER) is recognized as an organelle that participates in folding secretory and membrane proteins. The ER responds to stress by upregulating ER chaperones, but prolonged and/or excess ER stress leads to apoptosis. However, the potential role of ER stress in pathophysiological hearts remains unclear. Mice were subjected to transverse aortic constriction (TAC) or sham operation. Echocardiographic analysis demonstrated that mice 1 and 4 weeks after TAC had cardiac hypertrophy and failure, respectively. Cardiac expression of ER chaperones was significantly increased 1 and 4 weeks after TAC, indicating that pressure overload by TAC induced prolonged ER stress. In addition, the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells increased, and caspase-3 was cleaved in failing hearts. The antagonism of angiotensin II type 1 receptor prevented upregulation of ER chaperones and apoptosis in failing hearts. On the other hand, angiotensin II upregulated ER chaperones and induced apoptosis in cultured adult rat cardiac myocytes. We also investigated possible signaling pathways for ER-initiated apoptosis. The CHOP- (a transcription factor induced by ER stress), but not JNK- or caspase-12-, dependent pathway was activated in failing hearts by TAC. Pharmacological ER stress inducers upregulated ER chaperones and induced apoptosis in cultured cardiac myocytes. Finally, mRNA levels of ER chaperones were markedly increased in failing hearts of patients with elevated brain natriuretic peptide levels. These findings suggest that pressure overload by TAC induces prolonged ER stress, which may contribute to cardiac myocyte apoptosis during progression from cardiac hypertrophy to failure.
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                Author and article information

                Journal
                Toxins (Basel)
                Toxins (Basel)
                toxins
                Toxins
                MDPI
                2072-6651
                30 August 2019
                September 2019
                : 11
                : 9
                : 507
                Affiliations
                Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha 410078, Hunan, China
                Author notes
                [* ]Correspondence: phfyang@ 123456csu.edu.cn ; Tel./Fax: +86-731-8480-5460
                Author information
                https://orcid.org/0000-0001-5687-0556
                Article
                toxins-11-00507
                10.3390/toxins11090507
                6783932
                31480273
                2d037b99-6bfd-45db-881e-cd6330934fc4
                © 2019 by the authors.

                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
                : 16 July 2019
                : 28 August 2019
                Categories
                Review

                Molecular medicine
                microcystins (mcs),toxicity,cardiovascular disease (cvd)
                Molecular medicine
                microcystins (mcs), toxicity, cardiovascular disease (cvd)

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