Mechanisms of Cardiovascular Toxicity Induced by Silver Nanoparticles: A Systematic Review of Preclinical Evidence.

Silver nanoparticles (AgNPs) have emerged as one of the most widely used nanomaterials in medical and consumer products, yet their cardiovascular safety remains inadequately characterized. While their antimicrobial properties are well-documented, accumulating evidence reveals that AgNPs pose a significant threat to the cardiovascular system. Exposure to AgNPs through inhalation, ingestion, or dermal contact enables these particles to enter systemic circulation, where they accumulate in cardiac and vascular tissues in a dose-, time-, and size-dependent manner. Once deposited, AgNPs initiate a cascade of pathological events, including oxidative stress, mitochondrial dysfunction, DNA damage, and disruption of calcium and sodium channel signaling. These molecular disturbances translate into physiological alterations such as bradycardia, atrioventricular conduction block, impaired contractility, and exacerbated ischemia-reperfusion injury. AgNPs also trigger endothelial activation, leading to upregulation of adhesion molecules, namely vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1) and recruitment of inflammatory cells, creating a proinflammatory and prothrombotic environment. Elevated cardiac biomarkers, including creatine kinase-MB fraction (CK-MB), brain natriuretic peptide (BNP), lactate dehydrogenase (LDH), and histopathological changes, including pericardial edema, myofibril disorganization, fibrosis, and inflammatory infiltration are consistently observed. Vascular dysfunction manifests as impaired vasorelaxation, enhanced vasoconstriction via endothelin-1 upregulation, thrombosis, and abnormal angiogenesis driven by vascular endothelial growth factor (VEGF) dysregulation. Although plant-based AgNPs have shown cardioprotective potential in limited studies, the overall evidence indicates significant cardiovascular risk. This systematic review synthesizes findings from 38 preclinical studies (35 in vivo, 3 in vitro), providing a comprehensive analysis of AgNP-induced cardiotoxicity with emphasis on oxidative stress, inflammation, and molecular dysregulation as core mechanistic drivers.