Table 3.

Summary of studies on the cardiovascular toxicity of purified cyanotoxins in mammals in vitro

Cyanotoxins	Cells or other models	Doses	Duration	Cardiovascular effects	References
MC-LR	Primary HUVECs	10, 20, 40 μM	24 h	Cell proliferation↓, apoptosis↑, migration↓, capillary-like structure formation↓, intracellular and mitochondrial ROS ↑, p-NF-κB↑, VCAM-1↑, ICAM-1↑, TNF-α↑	Shi et al. (2015)
MC-LR	Primary HUVECs	40 μM	24, 48 h	Cell viability↓, apoptosis↑, migration index↓, tube formation↓, ROS↑, SOD↓, GSH↓, MDA↑, nitrite↑, p-NF-κB↑, VCAM-1↑, ICAM-1↑, IL-6 ↑, TNF-α↑	Shi et al. (2017)
MC-LR	Primary HUVECs	2 μM	6 h	Endothelial monolayer permeability↑, morphological changes of VE-cadherin containing junctions, endocytosis of VE-cadherin↑, MCP-1, IL-6, IL-8, IL-1β, TNF-α and ICAM-1 mRNA↑, p-VE-cadherin protein↑, secreted IL-8 protein↑	Chen et al. (2018c)
MC-LR	HUVECs	40 μM	24 h	Apoptosis↑, caspase-3 and -9↑, MMP↓, mitochondrial Cyt c↓, cytoplasmic Cyt c↑, mitochondrial and cytoplasmic ROS↑, NRF2 protein and activity↓, HO-1↓	Shi et al. (2018)
MC-LR	HUVECs	50, 100, 500, 1000 nmol/L	24 h	Cell proliferation↓, G0/G1%↑, S%↓, OTM↑, SOD, CAT and GPX activities↓, MDA↑	Wang et al. (2018)
MC-LR	Rat H9C2 cardiomyocytes	10 μM	4, 8, 12, 16, 20, 24 h	Rhythmic genes bmal1, per1, per2 and rev-erbα mRNA↓, cry1 and cry2 mRNA↑↓, antioxidant genes ho-1 and catalase mRNA↑↓, SOD1 and SOD2 mRNA↑	Xu et al. (2018)
MC-LR	HUVECs	0.01, 0.05, 0.1, 0.5, 1 μM	24 h	Apoptosis↑, MMP↓, mitochondrial ROS↑, caspase-3 and -9 activities↑, cleaved caspase-3 and p53 proteins↑, PCNA protein ↑↓	Wang et al. (2019)
MC-LR	Rat thoracic aortic rings	100, 1000 nM	2 weeks	Microvessels↓, cell migration↓, cell transfer distance↓	Wang et al. (2021b)
MC-LR	HUVECs	1, 10, 100, 1000 nM	12, 24 h	Enclosed lumen↓, common node of enclosed lumen↓, circumference of enclosed lumen↓, total lumen area↓, distance of cell migration↓, morphological damage of microfilaments, hollow nucleus, fluorescence intensity of actin-myosin cytoskeleton↓, condensed chromatin	Wang et al. (2021b)
CYN	HUVECs	0.3, 0.375, 0.6, 0.75, 1.25, 1.5, 2.5, 5, 10, 20, 40 µg/mL	24, 48 h	Total protein content↓, neutral red uptake↓, MTS reduction↓, ROS↑, GCS↑, GSH↑, micro-structural and ultra-structural damage, nucleolar segregation, altered nuclei, degenerated Golgi apparatus, presence of granules and apoptosis↑	Gutiérrez-Praena et al. (2012b)
CYN	HUVECs	2, 20, 200, 2000 nM (0.9, 9, 90, 900 μg/L)	12, 24, 48 h	Cell viability↓, distance of migration↓, apoptosis↑, altered microfilaments morphology, cell area↓, cell perimeter, intracellular ROS↑, ITGB1, Rho, ROCK, VIM-1, Bcl-2 mRNA↓, MLC-1 and Bax mRNA↑, Bax/ Bcl-2↑	Wang et al. (2020a)
STX	Neonatal rat ventricular cardiomyocytes (NRVCs)	10, 50, 100, 200, 500, 1000 ng/mL	10 min	Field potential amplitude (FPA)↓, firing rate (FR)↓, field potential duration (FPD)↑, peak amplitude↓, rise time↑	Li et al. (2018)
LTX A	Rabbit thoracic aortic rings	1 µM	2 h	Slowly developing contraction	Robinson et al. (1991)

↑ increased, ↓ decreased, CAT catalase, CYN cylindrospermopsin, GCS γ-glutamyl-cysteine synthetase, GSH glutathione, GPX glutathione peroxidase, HUVECs human umbilical vein endothelial cells, LTX lyngbyatoxin, MC microcystin, MDA malondialdehyde, MMP mitochondrial membrane potential, MTS tetrazolium salt, OTM olive tail moment, ROS reactive oxidative species, SOD superoxide dismutase, STX saxitoxin