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Differences in atrial versus ventricular remodeling in dogs with ventricular tachypacing-induced congestive heart
Nessrine Hanna1, Sophie Cardin, Tack-Ki Leung
1Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
Insights
Congestive heart failure causes distinct atrial and ventricular remodeling. Atrial fibrosis, inflammation, and angiotensin-II levels increase more rapidly and severely than in ventricles.
Area of Science:
- Cardiology
- Pathology
- Molecular Biology
Background:
- Congestive heart failure (CHF) induces significant remodeling in both atria and ventricles.
- Existing research has not fully characterized the differences in remodeling between atrial and ventricular tissues during CHF.
Purpose of the Study:
- To investigate and compare the distinct remodeling processes occurring in atrial and ventricular tissues in a canine model of CHF.
- To elucidate the temporal and quantitative differences in pathological changes between the atrium and ventricle.
Main Methods:
- Induction of CHF in dogs via ventricular tachypacing for up to 5 weeks.
- Histopathological analysis of atrial and ventricular tissues to assess apoptosis, fibrosis, and inflammation.
- ELISA and Western blot techniques to measure angiotensin-II concentration and protein expression, including transforming growth factor-beta1.
Main Results:
- CHF induced significantly greater fibrosis in the left atrium compared to the left ventricle.
- Atrial tissues exhibited faster, larger, and more transient increases in apoptosis, inflammation, and cell death than ventricular tissues.
- Angiotensin-II and transforming growth factor-beta1 levels increased substantially in the atrium, with distinct temporal patterns compared to the ventricle.
Conclusions:
- Significant qualitative and quantitative differences exist in atrial versus ventricular remodeling during experimental CHF.
- These disparities in remodeling mechanisms may have critical implications for understanding CHF pathophysiology.
- Identifying these differences is crucial for developing targeted therapeutic strategies for CHF.
Background:
Congestive heart failure (CHF) causes arrhythmogenic remodeling in both atria and ventricles, but differences between atrial and ventricular remodeling in CHF have not been well characterized.
Methods And Results:
We examined atrial and ventricular tissues from dogs with CHF induced by ventricular tachypacing (220-240/min) for 0 (control) or 24 h, or 1, 2 or 5 weeks. Histopathology was used to assess apoptosis, fibrosis, white blood cell infiltration and cell death, ELISA to measure angiotensin-II concentration and Western blot to evaluate protein expression. Ventricular tachypacing-induced CHF was associated with substantially more fibrosis in left atrium (maximum 10 +/- 1% at 5 weeks) than in left ventricle (0.4 +/- 0.1% at 5 weeks, P < 0.01 versus left atrium). Tissue angiotensin-II concentration increased to steady state in atrial tissue at 24 h but increased more slowly in left ventricle, with a maximum that was significantly higher in atrium than ventricle. Ventricular tachypacing caused tissue apoptosis, inflammatory cell infiltration and cell death, with maximum changes in left atrium being faster, transient and larger than in left ventricle. Mitogen activated protein kinase activation was rapid (within 24 h) in left atrium, but smaller and slower (p38, c-Jun N-terminal kinase) or non-significant (extracellular signal-related kinase) in left ventricle. The 25-kDa activated form of transforming growth factor-beta1, a particularly important profibrotic mediator in atrium, increased significantly in left atrium, from 2.6 +/- 0.6 (control) to 9.2 +/- 1.7 (24 h) and 8.1 +/- 1.8 optical density units (1 week), but was not significantly changed in ventricle.
Conclusions:
There are qualitative and quantitative differences in atrial versus ventricular remodeling in experimental ventricular tachypacing-induced CHF, with potentially important consequences for understanding underlying mechanisms and developing new therapeutic approaches.
