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Silver nanoparticles are widely used in various industrial and biomedical applications; however, little is known about their potential cardiotoxicity after pulmonary exposure, particularly in hypertensive subjects. We assessed the cardiotoxicity of polyethylene glycol (PEG)-coated AgNPs in hypertensive (HT) mice. Saline (control) or PEG-AgNPs (0.5 mg/kg) were intratracheally (i.t.) instilled four times (on days 7, 14, 21, and 28 post-angiotensin II or vehicle [saline] infusion). On day 29, various cardiovascular parameters were evaluated. Systolic blood pressure and heart rate were higher in PEG-AgNPs-treated HT mice than in saline-treated HT or PEG-AgNPs-treated normotensive mice. The heart histology of PEG-AgNPs-treated HT mice had comparatively larger cardiomyocyte damage with fibrosis and inflammatory cells when compared with saline-treated HT mice. Similarly, the relative heart weight and the activities of lactate dehydrogenase and creatine kinase-MB and the concentration of brain natriuretic peptide concentration were significantly augmented in heart homogenates of HT mice treated with PEG-AgNPs compared with HT mice treated with saline or normotensive animals exposed to PEG-AgNPs. Similarly, the concentrations of endothelin-1, P-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 in heart homogenates were significantly higher than in the other two groups when HT mice were exposed to PEG-AgNPs. Markers of inflammation and oxidative and nitrosative stress were significantly elevated in heart homogenates of HT mice given PEG-AgNPs compared with HT mice treated with saline or normotensive animals exposed to PEG-AgNPs. The hearts of HT mice exposed to PEG-AgNPs had significantly increased DNA damage than those of HT mice treated with saline or normotensive mice treated with AgNPs. In conclusion, the cardiac injury caused by PEG-AgNPs was aggravated in hypertensive mice. The cardiotoxicity of PEG-AgNPs in HT mice highlights the importance of an in-depth assessment of their toxicity before using them in clinical settings, particularly in patients with pre-existing cardiovascular diseases.

Impact of Intratracheal Administration of Polyethylene Glycol-Coated Silver Nanoparticles on the Heart of Normotensive and Hypertensive Mice