Abstract 421: Alterations in Adherens Junction and Gap Junction Precede Desmosomes Remodeling During the Transition from Experimental Compensated Cardiac Hypertrophy to Decompensation
Hypertension causes cardiac hypertrophy, cardiac dysfunction, and heart failure (HF). The mechanisms implicated in the transition from physiological to pathological hypertrophy are not fully understood. Growing evidence points out to the role of inappropriate intercellular mechanical and electrical coupling in the pathogenesis of HF. We investigated adherens junction, desmosome and gap junction proteins and their potential role in the pathogenesis of HF in rats submitted to chronic abdominal aorta stenosis. Wistar rats were submitted to abdominal aorta stenosis and killed at 90 days post surgery: 60% presented hypertrophied hearts (HH) and 40% hypertrophied and dilated hearts (DH), as evaluated by echocardiography. Blood pressure was evaluated. The hearts were collected, Western blot (WB) and immunofluorescence (IF) were performed for cadherin, plakoglobin, B-catenin, desmoglein, desmocollin and connexin-43. Cardiac systolic function was evaluated using Vevo 2100 ultrasound system. Data were considered significant when p<0.05. Cadherin expression increased 55% in HH and decreased 33% in DH; plakoglobin increased 67% in HH and decreased 29% in DH; B-catenin increased 73% in HH and decreased 32% in DH; connexin-43 decreased 17% in HH and 32% in DH; desmocolin increased 57% only in HH group and no alteration in desmoglein expression was observed in both groups. Mean blood pressure increased 61% in HH and 59% in DH. Ejection fraction and fractional shortening decreased 45% and 41%, respectively, only in DH. These results suggest different sensitivity of the intercalated disc components: proteins of the adherens junction and gap junction are more sensitive than desmosomes proteins and present significant reduced expression. This reduced expression could contribute to the transition of the compensated cardiac hypertrophy to decompensation. These abnormal parameters may emerge as therapeutic targets to modulate the evolution of HF.
Author Disclosures: D. dos Santos: None. V. Blefari: None. F. Prado: None. C. Silva: None. R. Fazan Jr: None. H. Salgado: None. S. Ramos: None. C. Prado: B. Research Grant (includes principal investigator, collaborator, or consultant and pending grants as well as grants already received); Modest; FAPES 2009/17787-8; 2010-19216-5.
- © 2014 by American Heart Association, Inc.