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Cardiac structural remodeling in hypertensive cardiomyopathy
Si-Jia Sun1, Jia-Lu Yao1,2, Lang-Biao Xu1
1Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, People's Republic of China.
Summary
A new porcine model using deoxycorticosterone acetate, Western diet, and angiotensin II effectively mimics heart failure with preserved ejection fraction (HFpEF). This model reveals hypertension-induced atrial remodeling, particularly in the posterior wall.
Area of Science:
- Cardiovascular Research
- Preclinical Models
- Pharmacological Development
Background:
- Heart failure with preserved ejection fraction (HFpEF) significantly contributes to morbidity and mortality, affecting half of all heart failure cases.
- Effective preclinical models are crucial for developing pharmacological treatments for HFpEF.
- Current models may not fully recapitulate the complex pathophysiology of HFpEF.
Purpose of the Study:
- To develop and validate a novel porcine model for studying heart failure with preserved ejection fraction (HFpEF).
- To investigate the cardiac structural and functional changes induced by hypertension and hyperlipidemia in this model.
- To identify specific regions of atrial remodeling associated with hypertensive heart disease.
Main Methods:
- A porcine model was established using deoxycorticosterone acetate (DOCA), Western diet (WD), and angiotensin II infusion.
- Systolic blood pressure, echocardiography, and invasive pressure-volume loops were assessed at baseline, 12, and 18 weeks.
- Histological analysis was performed to evaluate cardiac structural remodeling, including fibrosis.
Main Results:
- Hypertensive animals exhibited significantly elevated systolic blood pressure (181 vs. 86 mmHg) compared to controls at 18 weeks.
- Concentric cardiac remodeling with thickened walls was observed, alongside a tendency towards declining left ventricular diastolic function.
- Histological analysis revealed increased fibrotic areas in hypertensive animals, with the posterior left atrial wall showing greater susceptibility to remodeling.
Conclusions:
- The developed porcine model adequately mimics key aspects of clinical HFpEF, including hypertension and cardiac remodeling.
- This model provides a valuable platform for preclinical testing of HFpEF therapies.
- Hypertension preferentially induces remodeling in the posterior wall of the left atrium, highlighting a specific vulnerability in atrial structure.
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