Mineralocorticoid Accelerates Transition to Heart Failure With Preserved Ejection Fraction Via “Nongenomic Effects”

• DOI: 10.1161/circulationaha.109.915215
• Publication Date: 2010-07-13T03:55:12Z
• Authors: Selma F. Mohammed; Tomohito Ohtani; Josef Korinek; Carolyn S.P. Lam; Katarina Larsen; Robert D. Simari; Maria L. Valencik; John C. Burnett; Margaret M. Redfield
• Keywords: Pressure overload; Mineralocorticoid; Cardiac Fibrosis; Hypertensive heart disease

Mechanisms promoting the transition from hypertensive heart disease to failure with preserved ejection fraction are poorly understood. When inappropriate for salt status, mineralocorticoid (deoxycorticosterone acetate) excess causes hypertrophy, fibrosis, and diastolic dysfunction. Because cardiac receptors protected binding by absence of 11-beta hydroxysteroid dehydrogenase, salt-mineralocorticoid-induced inflammation is postulated cause oxidative stress mediate effects. Although previous studies have focused on salt/nephrectomy in accelerating mineralocorticoid-induced effects, we hypothesized that associated sensitizes mineralocorticoid, dysfunction.Cardiac structure function, stress, receptor-dependent gene transcription were measured sham-operated transverse aortic constriction (studied 2 weeks later) mice without deoxycorticosterone acetate administration, all setting normal-salt diet. Compared sham mice, plus had mild hypertrophy fibrosis or Transverse displayed compensated increased (osteopontin NOX4 expression), normal systolic filling pressures, stiffness. similar left ventricular pressure fractional shortening but more dysfunction lung weights, consistent fraction. There was progressive activation markers across groups no evidence classic transcription.Pressure-overload excess, which promotes independently transcription.