Toll-Like Receptor 4 Inhibition Improves Oxidative Stress and Mitochondrial Health in Isoproterenol-Induced Cardiac Hypertrophy in Rats
| Autor: | Amit K. Dinda, Pankaj K. Bagul, Parmeshwar B. Katare, Sanjay K. Banerjee |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
lcsh:Immunologic diseases. Allergy
0301 basic medicine Agonist medicine.medical_specialty medicine.drug_class Immunology toll-like receptor 4 oxidative phosphorylation Inflammation Oxidative phosphorylation 030204 cardiovascular system & hematology Biology medicine.disease_cause Muscle hypertrophy Pathogenesis 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Immunology and Allergy Receptor Original Research isoproterenol cardiac hypertrophy lipopolysaccharide RS-LPS 030104 developmental biology Endocrinology TLR4 cardiovascular system medicine.symptom lcsh:RC581-607 Oxidative stress |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, Vol 8 (2017) |
| ISSN: | 1664-3224 |
| Popis: | Background- Inflammation remains a crucial factor for progression of cardiac diseases and cardiac hypertrophy remains an important cause of cardiac failure over all age groups. As a key regulator of inflammation, toll like receptor 4 (TLR4) plays an important role in pathogenesis of cardiac diseases. Being an important regulator of innate immunity, the precise pathway of TLR4 mediated cardiac complications is yet to be established. Therefore, the primary objective of the present study was to find the role of TLR4 in cardiac hypertrophy and the molecular mechanism thereof. Methods- Cardiac hypertrophy was induced with administration of isoproterenol (5mg/kg/day, sc). TLR4 receptor inhibitor RS-LPS (lipopolysaccharide from the photosynthetic bacterium Rhodobacter sphaeroides; 5 microgram/day) and agonist LPS (Lipopolysaccharide from Escherichia coli; 3.12 microgram/day) were administered through osmotic pump along with isoproterenol. Cardiac hypertrophy as well as oxidative stress and mitochondrial parameters were evaluated. Results- Cardiac hypertrophy was confirmed with increased heart weight/body weight ratio as well as assessment of hypertrophic markers in heart. There was a marked increase in the TLR4 expression and oxidative stress along with mitochondrial dysfunction in ISO group. TLR4 inhibition significantly decreased heart weight/body weight ratio and ANP, collagen and β-MHC expression and restored the disturbed cellular antioxidant flux. The mitochondrial perturbations that were observed in hypertrophy heart, was normalized after administration of TLR4 inhibitor but not with the agonist. TLR4 agonism further exaggerated the oxidative stress in heart and hence accelerated the disease development and progression. Conclusively- Our data shows that, increased TLR4 ligand pool in cardiac hypertrophy may exaggerate the disease progression. However, inhibition of TLR4 attenuated cardiac hypertrophy through reduced cardiac redox imbalance and mitochondrial dysfunction. |
| Databáze: | OpenAIRE |
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