Research Progress on Cellular Behavior of CaSR in Cardiovascular Diseases

Xinyu Liu¹Tao Xie²Javeria Qadir³Shuang Li¹Tianshuang Xu⁴Yang Lu⁵Xiaotian Ge⁶Hui Yuan^6*

• ¹School of Basic Medical Sciences, Mudanjiang Medical University, Mudanjiang, China
• ²School of Clinical Medicine, Jiamusi University, Jiamusi, China
• ³Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan
• ⁴Department of Immunology, Mudanjiang Medical University, Mudanjiang, China
• ⁵Department of Gastroenterology, Mudanjiang Traditional Chinese Medicine Hospital, Mudanjiang, China
• ⁶School of Stomatology, Mudanjiang Medical University, Mudanjiang, China

Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide, posing a major burden on global health system. Despite advancements in diagnosis and therapy, the underlying cellular and molecular mechanisms contributing to the development and progression of CVDs are not fully understood(1). Among them, the dysregulation of calcium signal transduction, as a crucial pathological physiological process, is receiving increasing attention, particularly in terms of calcium signal imbalance and its impact on the survival and function of cardiac cells. Therefore, Calcium-sensing receptor (CaSR) can serve as an important target for the treatment of cardiovascular diseases. CaSR is a cell surface receptor that functions by sensing the concentration of Ca2+ in the extracellular matrix (ECM), thus, serving as a primary regulator of calcium homeostasis. Calcium is an important ion in the cells, highly ubiquitous and an integral intracellular messenger that participates in various biological processes(2-4). The alterations in extracellular Ca2+ concentration can affect normal cellular activities and physiological functions of these systems. Several cardiovascular conditions, including hypertension, atherosclerosis, cardiac hypertrophy, myocardial infarction (MI), and vascular calcification, have been associated with altered CaSR expression or signaling. These associations have spurred growing interest in the therapeutic modulation of CaSR using pharmacological agents such as calcimimetics and calcilytics. While these agents have shown potential in preclinical models, their use in cardiovascular therapy remains limited due to concerns regarding systemic side effects and inconsistent outcomes(5,6). Given the expanding body of literature on CaSR's involvement in cardiovascular health and disease, a comprehensive review of its cellular biological behaviors is timely and necessary. This article aims to summarize current knowledge on CaSR expression and function in cardiovascular cell types, discuss its role in various cardiovascular pathologies, highlight contradictory findings and research gaps, and explore the therapeutic potential of CaSR-targeted interventions. Such insights may help pave the way toward more targeted and effective strategies for managing CVDs.