Cardiovascular calcification (CVC) is a pathological process characterized by the presence of calcium phosphate or oxalate crystals in the vascular wall, cardiac valves or myocardium. CVC is a hallmark feature of atherosclerosis and calcific aortic valve disease and is frequently observed in metabolic disorders such as diabetes mellitus and chronic kidney disease, as well as in ageing. Besides these acquired disorders, CVC is also observed in rare Mendelian diseases such as pseudoxanthoma elasticum (PXE), generalized arterial calcification of infancy (GACI), arterial calcification due to CD73 deficiency (ACDC) and Hutchinson-Gilford progeria syndrome (HGPS). CVC are reputed to increase arterial stiffness and reduced end-organ perfusion resulting in myocardial ischemia, ischemic stroke and peripheral arterial disease, and are also influencing atheromatous plaque vulnerability, and impairs cardiac valve functioning, hence significantly contributing to cardiovascular morbidity and mortality.

The pathophysiology of CVC is characterized by an imbalance between pro- and anti-calcifying mechanisms including cell transdifferentiation (vascular smooth muscle, valve interstitial cells and endothelial cells), disturbed mineral homeostasis, inflammation, and an increasing number of local and systemic pro and anti-calcifying factors (e.g. fetuin-A, pyrophosphate, calciproteins, …). Molecular drivers of CVC include bone morphogenetic protein (BMP) signaling, upregulation of tissue-nonspecific alkaline phosphatase (TNAP), extracellular matrix degradation by metalloproteinases (MMP), increased oxidative stress and production of reactive oxygen species (ROS), progressive DNA damage and cellular senescence, and secretion of calcifying extracellular vesicles. The development and implementation of novel animal models including genetically engineered rodent, pig and zebrafish strains has greatly accelerated biomedical research into CVC. However, despite these recent advances no effective treatments preventing, halting or reversing CVC currently exist, thus presenting a high unmet medical need.

Additionally, research into CVC is hampered by knowledge gaps regarding the clinical phenotypes and natural history of CVC disorders, while reliable biomarkers for disease progression and therapeutic monitoring are also lacking.

Addressing these challenges is crucial for advancing our understanding of CVC and accelerating the development of anti-calcifying compounds which hold potential for mitigating CVC burden, ultimately improving overall cardiovascular health. This Research Topic aims to explore the complex landscape of cardiovascular calcification, emphasizing disease mechanisms, varied clinical phenotypes, and innovative therapeutic approaches.

This collection will delve into:
-Molecular Pathways: Investigating the biochemical cascades and genetic predispositions underlying calcification, with an emphasis on novel biomarkers and pathophysiological insights.
-Clinical Phenotyping: Differentiating between the diverse clinical manifestations of calcification in cardiovascular diseases, contributing to personalized medicine approaches.
-Therapeutic Innovations: Evaluating cutting-edge treatments, including pharmacological interventions and advanced surgical techniques, to manage and potentially reverse calcification.
- Novel Diagnostic Tools: Developing and validating imaging technologies and non-invasive diagnostics to improve early detection and patient outcomes.

Curated by experts Lukas Nollet, Olivier Vanakker, and Georges Lefthériotis, this topic seeks to foster interdisciplinary collaboration and translate research findings into impactful clinical applications.

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Frontiers in Cardiovascular Medicine

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