Reduction of gap and adherens junction proteins and intercalated disc structural remodeling in the hearts of mice submitted to severe...

• Grant number: 07/04564-5
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Start date: September 01, 2007
• End date: September 30, 2007
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Marcos Antonio Rossi
• Grantee: Marcos Antonio Rossi
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Objective: The purpose of the present investigation was to test the hypothesis that alterations in cell communication and mechanical coupling between neighboring cardiomyocytes could contribute to myocardial depression in sepsis.Design: Controlled animal study. Setting: University research laboratory. Subjects: Male C57BL/6 mice.Interventions: Mice were submitted to moderate and severe septic injury by cecal ligation and puncture (CLP). Measurement and Main Results: Severe septic injury was accompanied by large number of bacteria in the peritoneal cavity and blood, high levels of TNFα and MIP-1α in the septic focus and serum, marked hypotension, and high mortality rate. Western blot analysis and immunofluorescence showed a marked decrease of key gap and adherens junction proteins (connexin43 and N-cadherin, respectively) in mice submitted to severe septic injury. These changes may result in the loss of intercalated disc structural integrity characterized in the electron microscopic study by partial separation or dehiscence of gap junction and adherens junctions. Conclusions: Our data provide important insight regarding the alterations in intercalated disc components resulting from severe septic injury. The intercalated disc remodeling under both protein expression and structural headings in experimental severe sepsis induced by CLP may be partly responsible for myocardial depression in sepsis/septic shock. Although further electrophysiological studies in animals and man are needed to determine the impact of these alterations on myocardial conduction velocity, the abnormal parameters may emerge as therapeutic targets and their modulation might provide beneficial effects on future cardiovascular outcomes and mortality in sepsis. (AU)