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Cardiovascular Effects of Snake Toxins: Cardiotoxicity and Cardioprotection

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1. Title Title of document Cardiovascular Effects of Snake Toxins: Cardiotoxicity and Cardioprotection
2. Creator Author's name, affiliation, country Alexey S. Averin; Institute of Cell Biophysics of the Russian Academy of Sciences PSCBR RA; Россия
2. Creator Author's name, affiliation, country Yuri N. Utkin; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences; Россия
3. Subject Discipline(s)
3. Subject Keyword(s) bradykinin-potentiating peptides; snake venom; cardioprotector; cardiotoxin; natriuretic peptide; cardiovascular system
4. Description Abstract

Snake venoms, as complex mixtures of peptides and proteins, affect various vital systems of the organism. One of the main targets of the toxic components from snake venoms is the cardiovascular system. Venom proteins and peptides can act in different ways, exhibiting either cardiotoxic or cardioprotective effects. The principal classes of these compounds are cobra cardiotoxins, phospholipases A2, and natriuretic, as well as bradykinin-potentiating peptides. There is another group of proteins capable of enhancing angiogenesis, which include, e.g., vascular endothelial growth factors possessing hypotensive and cardioprotective activities. Venom proteins and peptides exhibiting cardiotropic and vasoactive effects are promising candidates for the design of new drugs capable of preventing or constricting the development of pathological processes in cardiovascular diseases, which are currently the leading cause of death worldwide. For example, a bradykinin-potentiating peptide from Bothrops jararaca snake venom was the first snake venom compound used to create the widely used antihypertensive drugs captopril and enalapril. In this paper, we review the current state of research on snake venom components affecting the cardiovascular system and analyse the mechanisms of physiological action of these toxins and the prospects for their medical application.

5. Publisher Organizing agency, location Acta Naturae Ltd
6. Contributor Sponsor(s) RFBR (20-14-50134)
7. Date (DD-MM-YYYY) 15.11.2021
8. Type Status & genre Peer-reviewed Article
8. Type Type Review Article
9. Format File format
10. Identifier Uniform Resource Identifier https://actanaturae.ru/2075-8251/article/view/11375
10. Identifier Digital Object Identifier (DOI) 10.32607/actanaturae.11375
11. Source Title; vol., no. (year) Acta Naturae; Vol 13, No 3 (2021)
12. Language English=en ru
13. Relation Supp. Files Fig. 1. Amino acid sequences of BPPs (A) and the structure of captopril (B). Z is a pyroglutamic acid residue (165KB) doi: 10.32607/20758251-2021-13-3-4-14-2845
Fig. 2. Amino acid sequences of NPs. Identical amino acid residues are underlined. The disulfide bond is shown as a line connecting cysteine residues. hANP and hBNP are human atrial and brain NPs, respectively. hCNP is the human C-type NP. DNP is an NP from Dendroaspis angusticeps mamba venom (UniProtKB -P28374), CA-CNP is a C-type NP from Crotalus atrox venom (P0CV87), COA-NP2 is an NP from C. oreganus abyssus venom (B3EWY2), and PNP is an NP from Pseudocerastes persicus venom (P82972) (188KB) doi: 10.32607/20758251-2021-13-3-4-14-2846
Fig. 3. Amino acid sequences of endothelins and sarafotoxins. Disulfide bonds are shown as lines connecting cysteine residues. END1 (UniProtKB – P05305) and END2 (P20800) are human endothelin 1 and 2, respectively. SRTX-A (UniProtKB – P13208), SRTX-B (P13208), SRTX-C (P13208), SRTX-E (P13208), and SRTX-D (P13211) are sarafotoxins A, B, C, E, and D from A. engaddensis venom, respectively. SRTX-i1 (P0DJK0) is sarafotoxin i1 from A. irregularis venom; SRTX-m (Q6RY98) is sarafotoxin m from the venom of A. microlepidota microlepidota (205KB) doi: 10.32607/20758251-2021-13-3-4-14-2847
Fig. 4. Spatial structures of some three-finger toxins. Cardiotoxin II from Naja oxiana (PDB code – 1CB9), β-cardiotoxin from Ophiophagus hannah (3PLC), toxin ρ-Da1a from Dendroaspis angusticeps (4IYE), and weak toxin WTX from Naja kaouthia (2MJ0). The structures of cardiotoxin II and WTX were established by NMR, the structures of β-cardiotoxin and toxin ρ-Da1a were determined by X-ray analysis. Disulfide bonds are highlighted in yellow (381KB) doi: 10.32607/20758251-2021-13-3-4-14-2848
14. Coverage Geo-spatial location, chronological period, research sample (gender, age, etc.)
15. Rights Copyright and permissions Copyright (c) 2021 Averin A.S., Utkin Y.N.
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