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
Insights
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.
Abstract:
Aldosterone infusion results in left ventricular hypertrophy (LVH) and hypertension and may involve profibrotic and proinflammatory mechanisms. In turn, hypertension is the major cause of diastolic heart failure (HF). Adiponectin, an adipose-derived plasma protein, exerts antiinflammatory and anti-hypertrophic effects and is implicated in the development of hypertension and systolic HF. We thus tested the hypothesis that hypoadiponectinemia in aldosterone-induced hypertension exacerbated cardiac remodeling and diastolic HF. Wild-type (WT) or adiponectin-deficient (APNKO) mice underwent saline or aldosterone infusion and uninephrectomy and were fed 1% salt water for 4 wk. Blood pressure was increased in aldosterone-infused WT (132 +/- 2 vs. 109 +/- 3 mm Hg; P < 0.01) and further augmented in APNKO mice (140 +/- 3 mm Hg; P < 0.05 vs. aldosterone-infused WT). LVH was increased in aldosterone-infused WT vs. WT mice (LV/body weight ratio, 4.8 +/- 0.2 vs. 4.1 +/- 0.2 mg/g) and further increased in aldosterone-infused APNKO mice (LV/body weight ratio, 6.0 +/- 0.4 mg/g). Left ventricular ejection fraction was not decreased in either aldosterone-infused WT or APNKO hearts. Pulmonary congestion however was worse in APNKO mice (P < 0.01). The ratio of early ventricular filling over late ventricular filling (E/A) and the ratio of mitral peak velocity of early filling to early diastolic mitral annular velocity (E/e'), measures of diastolic function, were increased in aldosterone-infused WT hearts and further increased in APNKO hearts (P < 0.05 for both). Renal function and cardiac fibrosis were no different between both aldosterone-infused groups. Aldosterone increased matrix metalloproteinase-2 expression in WT hearts (P < 0.05 vs. WT and P < 0.01 vs. APNKO). Myocardial atrial natriuretic peptide, interferon-gamma, and TNF-alpha expression were increased in aldosterone-infused WT hearts. Expression of these proteins was further increased in aldosterone-infused APNKO hearts. Therefore, hypoadiponectinemia in hypertension-induced diastolic HF exacerbates LVH, diastolic dysfunction, and diastolic HF. Whether or not adiponectin replacement prevents the progression to diastolic HF will warrant further study.
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