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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, RESULTS. Meshes: Age Factors, Animals, Cardiomegaly, Diastole, Disease Models, Animal, Elasticity, Exercise Tolerance, Heart Failure, Diastolic, Immunoglobulins, Male, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Microscopy, Immunoelectron, Phenotype, Phosphorylation, Protein Kinases, Protein Structure, Tertiary, Sarcomeres.
user
Does shortening of the elastic tandem immunoglobulin segment of titin lead to diastolic dysfunction? Context: Diastolic dysfunction is a poorly understood but clinically pervasive syndrome that is characterized by increased diastolic stiffness. Titin is the main determinant of cellular passive stiffness. However, the physiological role that the tandem immunoglobulin (Ig) segment of titin plays in stiffness generation and whether shortening this segment is sufficient to cause diastolic dysfunction need to be established. We generated a mouse model in which 9 Ig-like domains (Ig3-Ig11) were deleted from the proximal tandem Ig segment of the spring region of titin (IG KO). Exon microarray analysis revealed no adaptations in titin splicing, whereas novel phospho-specific antibodies did not detect changes in titin phosphorylation. Passive myocyte stiffness was increased in the IG KO, and immunoelectron microscopy revealed increased extension of the remaining titin spring segments as the sole likely underlying mechanism. Diastolic stiffness was increased at the tissue and organ levels, with no consistent changes in extracellular matrix composition or extracellular matrix-based passive stiffness, supporting a titin-based mechanism for in vivo diastolic dysfunction. Additionally, IG KO mice have a reduced exercise tolerance, a phenotype often associated with diastolic dysfunction.
assistant
Increased titin-based passive stiffness is sufficient to cause diastolic dysfunction with exercise intolerance. Final Decision: yes