- A study, published in European Journal of Pharmacology, shows that paricalcitol, a vitamin D receptor activator, attenuates cellular injury mechanisms associated with ferroptosis and helps preserve cardiac function in an experimental model of ischemia-reperfusion
Researchers from the Cardiovascular Pathophysiology Group at the Institute for Biomedical Research Sols-Morreale (IIBM), CSIC-UAM, led by Dr. Carmen Delgado and Dr. Lisardo Boscá, in collaboration with researchers from the Institute of Molecular Biology and Genetics (IBGM) CSIC-University of Valladolid, both groups being members of the CIBER consortium of the ISCIII, and researchers from other institutions, have identified a potential new pharmacological strategy to protect the heart against injury associated with the restoration of blood flow following myocardial infarction.
Acute myocardial infarction occurs when the blood supply to a region of the heart is interrupted, depriving cardiac cells of oxygen and nutrients. Rapid restoration of blood flow through procedures such as primary percutaneous coronary intervention (PCI) is essential to limit infarct size and improve patient survival. However, the restoration of blood flow can also trigger additional processes of cellular damage, collectively known as ischemia-reperfusion injury, which contribute to the deterioration of cardiac function. One of the mechanisms involved is ferroptosis, a form of regulated, iron-dependent cell death characterized by the oxidation of lipids in cellular membranes.
The research team used an experimental mouse model of myocardial ischemia-reperfusion, combined with studies in human cardiac-derived cells. Using cardiac magnetic resonance imaging, gene expression analysis, lipidomics, and electron microscopy, the researchers observed that ischemia-reperfusion induces alterations associated with ferroptosis, including the accumulation of oxidized phospholipids and structural damage to mitochondria, the organelles responsible for cellular energy production.
Treatment with paricalcitol reduced the accumulation of oxidized lipids, attenuated mitochondrial alterations, and modulated the expression of genes involved in oxidative stress and ferroptosis. These effects were accompanied by reduced ventricular dilation and attenuation of the deterioration in cardiac contractile function during the early stages following ischemic injury. This preclinical study opens new avenues for the development of pharmacological strategies aimed at limiting cardiac injury associated with the restoration of blood flow following myocardial infarction.
Cover image: Transmission electron microscopy images of mouse cardiac tissue. From left to right: untreated baseline (Baseline), paricalcitol-treated baseline, seven days after ischemia/reperfusion, and seven days after ischemia/reperfusion with paricalcitol treatment. The upper panels show representative high-magnification images (40,000×; scale bar, 1 μm) illustrating mitochondrial ultrastructure. The lower panels show lower-magnification images (10,000×; scale bar, 2 μm) illustrating the organization of interfibrillar mitochondria and sarcomeres.
Reference: Ramiro-Ponce V, Fedichkina R, Martín-Nunes L, et al. “Pharmacological activation of vitamin D receptor by paricalcitol attenuates ferroptosis-associated myocardial injury after ischemia-reperfusion.” European Journal of Pharmacology. 2026 Oct 23;1039:179472. doi: 10.1016/j.ejphar.2026.179472.