The Yin and Yang of copper in cardiovascular health and disease.

Copper (Cu), an essential micronutrient and transition metal, plays a critical role in numerous biological processes, particularly within the cardiovascular system. Both cuprous (Cu⁺) and cupric (Cu2⁺) forms of copper are extensively involved in regulating key cellular biological processes, including apoptosis, autophagy, cell proliferation, mitochondrial dysfunction, inflammation, immune dysregulation, glucose/lipid metabolism and gut microbiota. Maintaining copper homeostasis is fundamental for cardiovascular health. Growing evidence indicates that copper dyshomeostasis may act as a critical trigger for the onset and progression of cardiovascular diseases (CVDs), such as atherosclerosis, stroke, hypertension, cardiac hypertrophy, heart failure, ischemia/reperfusion injury, and myocardial infarction. Accordingly, targeting copper dysregulation may offer a promising strategy for CVDs therapy. In this review, we summarize the essential functions of copper and examine how its dysregulation contributes to cellular dysfunction and the pathophysiology of CVDs. We further explore the molecular mechanisms by which copper imbalance drives CVD pathogenesis. Additionally, recent advances and current challenges in copper-targeted therapeutic strategies are discussed. By elucidating the Yin-Yang role of copper in cardiovascular biology, this review may provide a comprehensive foundation for future research and therapeutic development.