Metalloproteinases: key and common mediators of multiple GPCRs and candidate therapeutic targets in models of hypertensive cardiac disease

Abstract

Hypertensive cardiac disease remains a major cause of death worldwide because its typically complex etiology renders current treatments ineffective. Primary causative factors include environmental stressors, genetic predisposition and metabolic morbidities such as obesity and diabetes. These factors all trigger a systemic pathological production of agonists of G-proteincoupled receptors (GPCRs). When produced in excess, GPCR agonists transactivate many metalloproteinases, which relay agonist signaling. Here we review evidence supporting a global therapeutic concept for treatment of hypertensive cardiac disease with complex or unknown etiology by targeting common mediators of multiple GPCRs such as metalloproteinases and their downstream effectors.

Matrix Metalloproteinase-2 Mediates a Mechanism of Metabolic Cardioprotection Consisting of Negative Regulation of the Sterol Regulatory Element–Binding Protein-2/3-Hydroxy-3-Methylglutaryl-CoA Reductase Pathway in the Heart

“…Running Title: MMP-2/HMGCR cardioprotective pathway Xiang Wang (1,5) , Evan Berry (1,5) , Samuel Hernandez-Anzaldo (1,5) , Zamaneh Kassiri (2,3,4,5) and Carlos Fernandez-Patron (1,3,4,5) Xiang Wang, Evan Berry, and Samuel Hernandez-Anzaldo contributed equally.…”

Confirming therapeutic target of protopine using immobilized β2‐adrenoceptor coupled with site‐directed molecular docking and the target‐drug interaction by frontal analysis and injection amount–dependent method

“…This is illustrated by the development of stationary phases containing immobilized σ ‐, κ ‐, and μ ‐opioid receptors, P 2 Y‐like receptor GRP17, and α 1 ‐ and β 2 ‐adrenergic receptor ( β 2 ‐AR) . These immobilized G protein‐coupled receptor columns have proved to be stable and adaptable to standard chromatographic equipment and mass spectrometers …”

“…[22][23][24][25] These immobilized G protein-coupled receptor columns have proved to be stable and adaptable to standard chromatographic equipment and mass spectrometers. 26,27 Protopine is one of the isoquinolin alkaloids occurring in opium poppy, Corydalis tubers, and other plants of the family papaveraceae used as remedy for cough, bronchitis, and asthma as a result of the antispasmodic properties. 28 This implies that protopine has potential to be a specific ligand of β 2 -AR according to the functions of the receptor.…”

Immobilised Histidine Tagged β2-Adrenoceptor Oriented by a Diazonium Salt Reaction and Its Application in Exploring Drug-Protein Interaction Using Ephedrine and Pseudoephedrine as Probes

“…G-protein coupled receptors (GPCRs) are the largest and most diverse superfamily of integral membrane receptors due to their crucial role in curing varied diseases [3]–[5] and being the most important class of drug targets [6].…”

“…The interactions between a protein and a drug are of growing interest due to the role in elucidating protein functions, explaining drug action mechanisms and discovering novel drug candidates [1] , [2] . G-protein coupled receptors (GPCRs) are the largest and most diverse superfamily of integral membrane receptors due to their crucial role in curing varied diseases [3] – [5] and being the most important class of drug targets [6] .…”