Khurrum Shahzad1,2, Shrey Kohli1, Moh'd Mohanad Al-Dabet1, Berend Isermann1. 1. Institute of Clinical Chemistry and Pathobiochemistry, Otto-von-Guericke-University, Magdeburg, Germany. 2. Department of Biotechnology, University of Sargodha, Sargodha, Pakistan.
Abstract
PURPOSE OF REVIEW: The serine protease activated protein C (aPC) was initially characterized as an endogenous anticoagulant, but in addition conveys anti-inflammatory, barrier-protective, and pro cell-survival functions. Its endogenous anticoagulant function hampered the successful and continuous implantation of aPC as a therapeutic agent in septic patients. However, it became increasingly apparent that aPC controls cellular function largely independent of its anticoagulant effects through cell-specific and context-specific receptor complexes and intracellular signaling pathways. The purpose of this review is to outline the mechanisms of aPC-dependent cell signaling and its intracellular molecular targets. RECENT FINDINGS: With the advent of new therapeutic agents either modulating directly and specifically the activity of coagulation proteases or interfering with protease-activated receptor signaling a better understanding not only of the receptor mechanisms but also of the intracellular signaling mechanisms controlled by aPC in a disease-specific and context-specific fashion, is required to tailor new therapeutic approaches based on aPC's anti-inflammatory, barrier-protective, and pro cell-survival functions. SUMMARY: This review summarizes recent insights into the intracellular signaling pathways controlled by aPC in a cell-specific and context-specific fashion. We focus on aPC-mediated barrier protection, inhibition of inflammation, and cytoprotecting within this review.
PURPOSE OF REVIEW: The serine protease activated protein C (aPC) was initially characterized as an endogenous anticoagulant, but in addition conveys anti-inflammatory, barrier-protective, and pro cell-survival functions. Its endogenous anticoagulant function hampered the successful and continuous implantation of aPC as a therapeutic agent in septic patients. However, it became increasingly apparent that aPC controls cellular function largely independent of its anticoagulant effects through cell-specific and context-specific receptor complexes and intracellular signaling pathways. The purpose of this review is to outline the mechanisms of aPC-dependent cell signaling and its intracellular molecular targets. RECENT FINDINGS: With the advent of new therapeutic agents either modulating directly and specifically the activity of coagulation proteases or interfering with protease-activated receptor signaling a better understanding not only of the receptor mechanisms but also of the intracellular signaling mechanisms controlled by aPC in a disease-specific and context-specific fashion, is required to tailor new therapeutic approaches based on aPC's anti-inflammatory, barrier-protective, and pro cell-survival functions. SUMMARY: This review summarizes recent insights into the intracellular signaling pathways controlled by aPC in a cell-specific and context-specific fashion. We focus on aPC-mediated barrier protection, inhibition of inflammation, and cytoprotecting within this review.
Authors: Atsuki Yamashita; Yuqi Zhang; Michel F Sanner; John H Griffin; Laurent O Mosnier Journal: J Thromb Haemost Date: 2020-03-05 Impact factor: 5.824
Authors: Eimear M Gleeson; Aisling M Rehill; Orla Willis Fox; Fionnuala Ni Ainle; Cormac J McDonnell; Hannah J Rushe; Seán McCluskey; James S O'Donnell; Roger J S Preston Journal: Blood Adv Date: 2020-06-09
Authors: Ihsan Gadi; Sameen Fatima; Berend Isermann; Khurrum Shahzad; Ahmed Elwakiel; Sumra Nazir; Moh'd Mohanad Al-Dabet; Rajiv Rana; Fabian Bock; Jayakumar Manoharan; Dheerendra Gupta; Ronald Biemann; Bernhard Nieswandt; Ruediger Braun-Dullaeus; Christian Besler; Markus Scholz; Robert Geffers; John H Griffin; Charles T Esmon; Shrey Kohli Journal: Circ Res Date: 2020-12-23 Impact factor: 17.367