title: Reduced expression of adherens and gap junction proteins can have a fundamental role in the development of heart failure following cardiac hypertrophy in rats.
abstract: Hypertension causes cardiac hypertrophy, cardiac dysfunction and heart failure (HF). The mechanisms implicated in the transition from compensated to decompensated cardiac hypertrophy are not fully understood. This study was aimed to investigate whether alterations in the expression of intercalated disk proteins could contribute to the transition of compensated cardiac hypertrophy to dilated heart development that culminates in HF. Male rats were submitted to abdominal aortic constriction and at 90 days post surgery (dps), three groups were observed: sham-operated animals (controls), animals with hypertrophic hearts (HH) and animals with hypertrophic + dilated hearts (HD). Blood pressure was evaluated. The hearts were collected and Western blot and immunofluorescence were performed to desmoglein-2, desmocollin-2, N-cadherin, plakoglobin, Bcatenin, and connexin-43. Cardiac systolic function was evaluated using the Vevo 2100 ultrasound system. Data were considered significant when p b 0.05. Seventy percent of the animals presented with HH and 30% were HD at 90 dps. The blood pressure increased in both groups. The amount of desmoglein-2 and desmocollin-2 expression was increased in both groups and no difference was observed in either group. The expression of N-cadherin, plakoglobin and B-catenin increased in the HHgroup and decreased in the HDgroup; and connexin-43 decreased only in theHDgroup. Therewas no difference between the ejection fraction and fractional shortening at 30 and 60 dps; however, they were decreased in the HD group at 90 dps. We found that while some proteins have increased expression accompanied by the increase in the cell volume associated with preserved systolic cardiac function in theHHgroup, these same proteins had decreased expression evenwithout significant reduction in the cell volume associated with decreased systolic cardiac function in HD group. The increased expression of desmoglein-2 and desmocollin-2 in both the HH and HD groups could work as a protective compensatory mechanism, helping tomaintain the dilated heart.We can hypothesize that inappropriate intercellular mechanical and electrical coupling associated with necrosis and/or apoptosis are important factors contributing to the transition to HF.
authors.affiliation: Department of Pathology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Daniele O
authors.initials: DO
authors.lastname: dos Santos
authors.affiliation: Department of Pathology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Valdecir
authors.initials: V
authors.lastname: Blefari
authors.affiliation: Department of Pathology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Fernanda P
authors.initials: FP
authors.lastname: Prado
authors.affiliation: Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Silva
authors.affiliation: Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Rubens
authors.initials: R
authors.lastname: Fazan
authors.affiliation: Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Helio C
authors.initials: HC
authors.lastname: Salgado
authors.affiliation: Department of Pathology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Simone G
authors.initials: SG
authors.lastname: Ramos
authors.affiliation: Department of Pathology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil. Electronic address: cibeleprado@usp.br.
authors.forename: Cibele M
authors.initials: CM
authors.lastname: Prado
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D006332:Cardiomegaly / Q000150:complications / Q000378:metabolism*; D017630:Connexins / Q000378:metabolism*; D017629:Gap Junctions / Q000502:physiology*; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism*; D006352:Heart Ventricles / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D017208:Rats, Wistar
chemical_list: D015820:Cadherins; D017630:Connexins
keywords: Adherens junction; Cardiac hypertrophy; Desmosome; Gap junction; Heart failure; Intercalated disk