Calcium-sensing receptor in the development and treatment of pulmonary hypertension

Mol Biol Rep. 2021 Jan;48(1):975-981. doi: 10.1007/s11033-020-06065-3. Epub 2021 Jan 4.

Abstract

Calcium-sensing receptor (CaSR) is widely involved in the cell proliferation, differentiation, migration, adhesion and apoptosis, which can affect the vascular remodeling in the humanbody. The main ligand of CaSR is extracellular Ca2+. CaSR has the physiological significance in Ca2+ homeostasis. Pulmonary vascular remodeling is one of the main histopathological changes of pulmonary hypertension (PH). The abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs) results in the pulmonary vascular remodeling. CaSR is an important regulator of [Ca2+]i. [Ca2+]i is the main cause of the excessive pulmonary vascular remodeling in patients with PH. In this review, it was conclued that the structure of CaSR was prone to explore the devolopment or the treatment of PH. It was found that the regulation of CaSR with some miRNA could inhibit the proliferation of PASMCs, and that CaSR could affect the occurrence of autophagy in PH. Therefore, CaSR would become a new therapeutic target to PH.

Keywords: Autophagy; Calcium-sensing receptor; Pulmonary arterial hypertension; Pulmonary artery smooth muscle cells; Pulmonary hypertension; Remodeling.

Publication types

  • Review

MeSH terms

  • Adamantane / analogs & derivatives*
  • Adamantane / therapeutic use
  • Animals
  • Autophagy / drug effects
  • Autophagy / genetics
  • Calcium / metabolism*
  • Calcium Channel Blockers / therapeutic use*
  • Cell Differentiation / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Gene Expression Regulation
  • Humans
  • Hypertension, Pulmonary / drug therapy
  • Hypertension, Pulmonary / genetics*
  • Hypertension, Pulmonary / metabolism
  • Hypertension, Pulmonary / pathology
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / metabolism
  • Myocytes, Smooth Muscle / pathology
  • Pulmonary Artery / drug effects
  • Pulmonary Artery / metabolism
  • Pulmonary Artery / pathology
  • Quinoxalines / therapeutic use*
  • Receptors, Calcium-Sensing / antagonists & inhibitors
  • Receptors, Calcium-Sensing / genetics*
  • Receptors, Calcium-Sensing / metabolism
  • Signal Transduction
  • Vascular Remodeling / drug effects*
  • Vascular Remodeling / genetics

Substances

  • 2-quinoxaline-carboxamide-N-adamantan-1-yl
  • CASR protein, human
  • Calcium Channel Blockers
  • Quinoxalines
  • Receptors, Calcium-Sensing
  • Adamantane
  • Calcium