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
Preclinical modeling of human disease with animals has not been standardized for many common pathologic processes. Assorted animal models are being used to investigate the pathogenesis, prevention, and treatment of disease processes. Certainly it is difficult to interpret the current literature because there are diverse and often irrelevant models being implemented. Some models are used for reasons of size or ease rather than the true modeling of a physiological process. Application to granting agencies and design of animal studies is difficult without standardization of the ideal preclinical model for disease states. The current article addresses the preclinical animal modeling of osteoporosis, infection, bone defects, and cartilage injury. This article is a discussion of the current literature, commonly used models, and suggests preferred preclinical models for future research design.
