ABSTRACT
Evidence has arisen in recent years suggesting that a tissue renin-angiotensin system (tRAS) is involved in the progression of various human diseases. This system contains two regulatory pathways: a pathological pro-inflammatory pathway containing the Angiotensin Converting Enzyme (ACE)/Angiotensin II (AngII)/Angiotensin II receptor type 1 (AGTR1) axis and a protective anti-inflammatory pathway involving the Angiotensin II receptor type 2 (AGTR2)/ACE2/Ang1-7/MasReceptor axis. Numerous studies reported the positive effects of pathologic tRAS pathway inhibition and protective tRAS pathway stimulation on the treatment of cardiovascular, inflammatory, and autoimmune disease and the progression of neuropathic pain. Cell senescence and aging are known to be related to RAS pathways. Further, this system directly interacts with SARS-CoV 2 and seems to be an important target of interest in the COVID-19 pandemic. This review focuses on the involvement of tRAS in the progression of the mentioned diseases from an interdisciplinary clinical perspective and highlights therapeutic strategies that might be of major clinical importance in the future.
Subject(s)
Angiotensin Receptor Antagonists/pharmacology , Angiotensin-Converting Enzyme Inhibitors/pharmacology , COVID-19/metabolism , Peptidyl-Dipeptidase A/metabolism , Receptors, Angiotensin/metabolism , Renin-Angiotensin System/drug effects , Aging/metabolism , Aging/pathology , Animals , Autoimmunity/drug effects , Autoimmunity/genetics , COVID-19/genetics , Cardiovascular Diseases/genetics , Cardiovascular Diseases/metabolism , Humans , Inflammation/drug therapy , Inflammation/genetics , Inflammation/metabolism , Receptors, Angiotensin/genetics , Regeneration/drug effects , Regeneration/genetics , Regeneration/physiology , Renin-Angiotensin System/genetics , Renin-Angiotensin System/physiology , Vulvodynia/immunology , Vulvodynia/physiopathology , COVID-19 Drug TreatmentABSTRACT
Total disc replacement using tissue-engineered intervertebral discs (TE-IVDs) may offer a biological alternative to treat radiculopathy caused by disc degeneration. A composite TE-IVD was previously developed and evaluated in rat tail and beagle cervical spine models in vivo. Although cell viability and tissue integration into host tissue were promising, significant implant displacement occurred at multiple spinal levels. The goal of the present study was to assess the effects of a resorbable plating system on the stiffness of motion segments and stability of tissue-engineered implants subjected to axial compression. Canine motion segments from levels C2/C3 to C5/C6 were assessed as intact (CTRL), after discectomy (Dx), with an implanted TE-IVD only (PLATE-), and with a TE-IVD combined with an attached resorbable plate (PLATE+). Segments under PLATE+ conditions fully restored separation between endplates and showed significantly higher compressive stiffness than segments under PLATE- conditions. Plated segments partially restored more than 25% of the CTRL motion segment stiffness. Plate attachment also prevented implant extrusion from the disc space at 50% compressive strain, and this effect was more significant in segments from levels C3/C4 when compared to segments from level C5/C6. These results suggest that stabilization of motion segments via resorbable plating assists TE-IVD retention in the disc space while allowing the opportunity for implants to fully integrate into the host tissue and achieve optimal restoration of spine biomechanics.
