Adiponectin deficiency, diastolic dysfunction, and diastolic heart failure.
Flora Sam1, Toni-Ann S Duhaney, Kaori Sato
1Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany Street, Boston, Massachusetts 02118, USA. flora.sam@bmc.org
Endocrinology
|October 24, 2009
Summary
Low adiponectin levels worsen cardiac remodeling and diastolic heart failure in hypertension. This study shows adiponectin deficiency exacerbates left ventricular hypertrophy and diastolic dysfunction in aldosterone-induced hypertension.
Area of Science:
- Cardiovascular Physiology
- Endocrinology
- Renal Physiology
Background:
- Aldosterone infusion causes hypertension and left ventricular hypertrophy (LVH), potentially via profibrotic and proinflammatory pathways.
- Hypertension is a primary driver of diastolic heart failure (HF).
- Adiponectin, an adipokine, has anti-inflammatory and anti-hypertrophic properties and influences cardiovascular health.
Purpose of the Study:
- To investigate if reduced adiponectin levels exacerbate cardiac remodeling and diastolic HF in the context of aldosterone-induced hypertension.
- To test the hypothesis that hypoadiponectinemia worsens aldosterone-induced cardiac dysfunction.
Main Methods:
- Wild-type (WT) and adiponectin-deficient (APNKO) mice were infused with aldosterone or saline, underwent uninephrectomy, and consumed a high-salt diet for 4 weeks.
- Measurements included blood pressure, left ventricular mass, cardiac function (ejection fraction, diastolic parameters E/A and E/e'), pulmonary congestion, cardiac fibrosis, and myocardial gene expression (MMP-2, ANP, IFN-γ, TNF-α).
Main Results:
- Aldosterone increased blood pressure and LVH in WT mice, with further augmentation in APNKO mice.
- Diastolic dysfunction (increased E/A and E/e' ratios) and pulmonary congestion were significantly worse in APNKO mice compared to WT mice with aldosterone infusion.
- While ejection fraction remained unchanged, inflammatory markers and MMP-2 expression were elevated in aldosterone-infused APNKO mice, indicating exacerbated cardiac stress.
Conclusions:
- Hypoadiponectinemia exacerbates left ventricular hypertrophy, diastolic dysfunction, and diastolic heart failure in the setting of aldosterone-induced hypertension.
- Adiponectin deficiency amplifies the detrimental cardiac effects of aldosterone, highlighting its protective role in hypertensive heart disease.
- Further research is needed to determine if adiponectin replacement therapy can prevent the progression of diastolic HF.
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