Calcium sensing receptor as a novel target for treatment of sepsis induced cardio‐renal syndrome: Need for exploring mechanisms

• Published in: Drug development research 2021-05, Vol.82 (3), p.305-308
• Main Authors: Yadav, Shubham, Gupta, Kirti, Deshmukh, Khalid, Bhardwaj, Loveinder, Dahiya, Ashish, Krishan, Pawan, Singh, Gaaminepreet
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Calcium; Calcium (intracellular); Calcium - metabolism; Calcium ions; Calcium-sensing receptors; Cardio-Renal Syndrome - etiology; Cardio-Renal Syndrome - therapy; Cardiomyocytes; Cell activation; Cell proliferation; Cell surface; Coronary artery disease; Health services; Heart diseases; Humans; Immune system; Inflammation; Inflammation Mediators - metabolism; Injury prevention; Kidneys; Leukocytes (neutrophilic); Lipopolysaccharides; Lymphocytes; Lymphocytes T; Mesangial cells; Mitochondria; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Neutrophil Activation; Neutrophils; Organs; Oxidative Stress; Podocytes - metabolism; Reactive oxygen species; Receptors; Receptors, Calcium-Sensing - metabolism; Renal function; Sepsis; Sepsis - complications
• ISSN: 0272-4391; 1098-2299
• DOI: 10.1002/ddr.21797

Calcium sensing receptor (CaSR) is localized in various organs and plays diverse physiological and pathological roles. Several scientific contributions have suggested the involvement of this cell surface receptor in cardiac and renal diseases. Sepsis is considered to be one of the major causes of ICU admissions. Cardiac dysfunction and acute kidney injury are major manifestations of sepsis and associated with reduced survival. Presently, the treatment approaches for management of sepsis induced cardiac depression and kidney injury are not satisfactory. Activation of CaSR has been demonstrated to induce cardiomyocyte damage upon lipopolysaccaharde (LPS) exposure by enhancing calcium ion levels, ROS (reactive oxygen species) production, promotion of inflammation and apoptosis. In addition, CaSR seems to be a critical regulator of intracellular calcium ion levels, which is directly implicated in induction of mitochondrial dysfunction and release of various pro‐apoptotic pathways during sepsis. Certain evidences have also documented the expression of CaSR on neutrophils and T lymphocytes, where it is involved in activation of neutrophils and induces apoptosis of immune cells. Moreover, the expression of CaSR has been confirmed in podocytes, mesangial cells, proximal tubular cells and its activation is responsible for podocyte effacement, mesangial cell proliferation and proximal tubular cell apoptosis. We have analyzed the existing evidences, and critically discussed the possible mechanisms underlying CaSR activation mediated cardiac and renal dysfunction in sepsis condition.