What is the clinical evidence from this study?

Study design: Other. Population: Aldosterone-induced hypertension and diastolic heart failure. Intervention: Adiponectin deficiency (APNKO) vs. Wild-type (WT) mice. Primary outcome: Blood pressure (p=<0.05).

October 23, 2009Open Access

Adiponectin Deficiency, Diastolic Dysfunction, and Diastolic Heart Failure

Q: What are the key findings of this study?

Adiponectin deficiency in mice with aldosterone-induced hypertension exacerbated blood pressure elevation (140 vs 132 mm Hg, P<0.05) and left ventricular hypertrophy compared to wild-type mice.

Key Result

Adiponectin deficiency in mice with aldosterone-induced hypertension exacerbated blood pressure elevation (140 vs 132 mm Hg, P<0.05) and left ventricular hypertrophy compared to wild-type mice.

Structured PICO

Does adiponectin deficiency exacerbate cardiac remodeling and diastolic heart failure in a mouse model of aldosterone-induced hypertension?

Population

Wild-type and adiponectin-deficient mice undergoing saline or aldosterone infusion and uninephrectomy, fed 1% salt water for 4 weeks.

Exposure

Aldosterone infusion, uninephrectomy, and 1% salt water for 4 weeks

Comparator

Saline infusion, uninephrectomy, and 1% salt water for 4 weeks

Outcome

Cardiac remodeling (left ventricular hypertrophy), diastolic function, and pulmonary congestionsurrogate

Adiponectin deficiency exacerbates left ventricular hypertrophy, diastolic dysfunction, and pulmonary congestion in a mouse model of aldosterone-induced hypertension.

Main Result

Absolute Event Rate: 140% vs 132%

p-value: p=<0.05

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.