Inducible NO synthase is constitutively expressed in porcine myocardium and its level decreases along with tachycardia-induced heart failure

Autor: Alicja Tomaszek, Liliana Kiczak, Robert Pasławski, Urszula Pasławska, Jacek Bania, Piotr Dziegiel, Maciej Zacharski, Katarzyna Michlik, Adrian Janiszewski
Rok vydání: 2016
Předmět:
0301 basic medicine
medicine.medical_specialty
Interleukin-1beta
Sus scrofa
Cardiomyopathy
Down-Regulation
Nitric Oxide Synthase Type II
030204 cardiovascular system & hematology
Mitochondrion
Biology
Nitric Oxide
medicine.disease_cause
Thiobarbituric Acid Reactive Substances
Ventricular Function
Left
Pathology and Forensic Medicine
Proinflammatory cytokine
Lipid peroxidation
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Malondialdehyde
Internal medicine
medicine
Animals
Aconitate Hydratase
Heart Failure
Myocardium
Cardiac Pacing
Artificial
General Medicine
medicine.disease
Disease Models
Animal
Oxidative Stress
030104 developmental biology
Endocrinology
medicine.anatomical_structure
chemistry
Ventricle
Heart failure
Disease Progression
Tachycardia
Ventricular
Ventricular Function
Right
Female
Lipid Peroxidation
Inflammation Mediators
Cardiology and Cardiovascular Medicine
Protein Processing
Post-Translational
Biomarkers
Oxidative stress
Zdroj: Cardiovascular Pathology. 25:3-11
ISSN: 1054-8807
DOI: 10.1016/j.carpath.2015.08.003
Popis: The adverse effects of oxidative stress and the presence of proinflammatory factors in the heart have been widely demonstrated mainly on rodent models. However, larger clinical trials focusing on inflammation or oxidative stress in heart failure (HF) have not been carried out. This may be due to differences in the anatomy and physiology of the cardiovascular system between small rodents and large mammals. Thus, we investigated myocardial inflammatory factors, such as inducible NO synthase (iNOS) and oxidative stress indices in female pigs with chronic tachycardia-induced cardiomyopathy.Homogenous female siblings of Large White breed swine (n=15) underwent continuous right ventricular (RV) pacing at 170bpm, whereas five sham-operated subjects served as controls. In the course of RV pacing, animals developed a clinical picture of HF and were euthanized at subsequent stages of the disease: mild, moderate and severe HF. Left ventricle (LV) sections were examined with electron microscopy. The relative expression of iNOS in LV was determined by quantitative PCR. The protein level of iNOS was determined by Western blotting and immunohistochemistry. The level of the S-nitrosylated (S-NO) protein in LV was determined after S-NO moieties were substituted by biotin, followed by a colorimetrical detection with streptavidin. Malondialdehyde (MDA), a marker of lipid peroxidation, was evaluated in the LV and serum using thiobarbituric acid. The aconitase activity (based on measurement of the concomitant formation of NADPH from NADP(+)), a marker of oxidative stress, was analyzed in mitochondrial and cytosolic LV fractions. The concentration of interleukin-1β (IL-1β) was measured in LV homogenates using enzyme-linked immunosorbent assay.RV pacing resulted in an impairment of LV systolic function, LV dilatation and neurohormonal activation. The electron microscopy revealed abnormalities within the cardiomyocytes of failing hearts, i.e. swollen mitochondria and myofibril derangement. iNOS was expressed in the control LV myocardium. The development of HF was accompanied by a decrease in iNOS mRNA (P.05), which was also reflected at a protein level, and a decrease in the protein S-nitrosylation (P.05). Both iNOS mRNA and S-NO relative moiety levels were inversely related to the dilatation of the LV (P.05). There was no difference in the concentration of MDA in the LV and serum. Similarly, no differences in the concentration of IL-1β LV were found between diseased and healthy animals. Aconitase activity was decreased only in the LV mitochondrial fraction of pigs with severe HF.iNOS was shown to be constitutively expressed within porcine LV. Its level decreases during the progression of systolic nonischemic HF in the pig model. Thus, it can be assumed that an up-regulation of proinflammatory factors is not involved in porcine tachycardia-induced cardiomyopathy and that the impact of oxidative stress may be restricted to the mitochondria in this HF model.
Databáze: OpenAIRE
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