The Goto Kakizaki rat: Impact of age upon changes in cardiac and renal structure, function

Autor: Kim A. Connelly, Robert A. Civitarese, Antoinette Bugyei-Twum, Patrick Meagher, Jean-Francois Desjardins, Hari Kosanam, Howard Leong-Poi, Golam Kabir, Aylin Visram, Xavier Alexander Lee, Yanling Zhang, Mark Gordon, Andrew Advani
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Aging
Physiology
Blood Pressure
Type 2 diabetes
030204 cardiovascular system & hematology
Kidney
ACE inhibitor therapy
Left ventricular hypertrophy
Muscle hypertrophy
Endocrinology
Medical Conditions
0302 clinical medicine
Diabetic cardiomyopathy
Medicine
030212 general & internal medicine
Mammals
Multidisciplinary
Ventricular Remodeling
Pharmaceutics
Organic Compounds
Monosaccharides
Eukaryota
Heart
Cardiovascular therapy
Animal Models
Chemistry
Experimental Organism Systems
Physiological Parameters
Vertebrates
Physical Sciences
Drug therapy
Anatomy
Research Article
Cardiac function curve
medicine.medical_specialty
Wistar Rats
Endocrine Disorders
Science
Carbohydrates
Research and Analysis Methods
Rodents
03 medical and health sciences
Model Organisms
Internal medicine
Diabetes mellitus
Diabetes Mellitus
Animals
Genetic Predisposition to Disease
Medicine and health sciences
business.industry
Myocardium
Body Weight
Organic Chemistry
Organisms
Chemical Compounds
Biology and Life Sciences
Kidneys
Renal System
medicine.disease
Fibrosis
Rats
Disease Models
Animal
Glucose
Blood pressure
Diabetes Mellitus
Type 2
Genetic Loci
Metabolic Disorders
Heart failure
Amniotes
Animal Studies
Cardiovascular Anatomy
Transcriptome
business
Zoology
Developmental Biology
Zdroj: PLoS ONE, Vol 16, Iss 6, p e0252711 (2021)
PLoS ONE
ISSN: 1932-6203
Popis: Background Patients with diabetes are at a high risk for developing cardiac dysfunction in the absence of coronary artery disease or hypertension, a condition known as diabetic cardiomyopathy. Contributing to heart failure is the presence of diabetic kidney disease. The Goto-Kakizaki (GK) rat is a non-obese, non-hypertensive model of type 2 diabetes that, like humans, shares a susceptibility locus on chromosome 10. Herein, we perform a detailed analysis of cardio-renal remodeling and response to renin angiotensin system blockade in GK rats to ascertain the validity of this model for further insights into disease pathogenesis. Methods Study 1: Male GK rats along with age matched Wistar control animals underwent longitudinal assessment of cardiac and renal function for 32 weeks (total age 48 weeks). Animals underwent regular echocardiography every 4 weeks and at sacrifice, early (~24 weeks) and late (~48 weeks) timepoints, along with pressure volume loop analysis. Histological and molecular characteristics were determined using standard techniques. Study 2: the effect of renin angiotensin system (RAS) blockade upon cardiac and renal function was assessed in GK rats. Finally, proteomic studies were conducted in vivo and in vitro to identify novel pathways involved in remodeling responses. Results GK rats developed hyperglycaemia by 12 weeks of age (p Conclusion By 48 weeks of age, the diabetic GK rat demonstrates evidence of preserved systolic function and impaired relaxation, along with cardiac hypertrophy, in the presence of hyperfiltration and elevated protein excretion. These findings suggest the GK rat demonstrates some, but not all features of diabetes induced “cardiorenal” syndrome. This has implications for the use of this model to assess preclinical strategies to treat cardiorenal disease.
Databáze: OpenAIRE
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