title: Hyperglycemic and hyperlipidemic conditions alter cardiac cell biomechanical properties.
abstract: Currently, many diabetic cardiomyopathy (DC) studies focus on either in vitro molecular pathways or in vivo whole-heart properties such as ejection fraction. However, as DC is primarily a disease caused by changes in structural and functional properties, such studies may not precisely identify the influence of hyperglycemia or hyperlipidemia in producing specific cellular changes, such as increased myocardial stiffness or diastolic dysfunction. To address this need, we developed an in vitro approach to examine how structural and functional properties may change as a result of a diabetic environment. Particle-tracking microrheology was used to characterize the biomechanical properties of cardiac myocytes and fibroblasts under hyperglycemia or hyperlipidemic conditions. We showed that myocytes, but not fibroblasts, exhibited increased stiffness under diabetic conditions. Hyperlipidemia, but not hyperglycemia, led to increased cFos expression. Although direct application of reactive oxygen species had only limited effects that altered myocyte properties, the antioxidant N-acetylcysteine had broader effects in limiting glucose or fatty-acid alterations. Changes consistent with clinical DC alterations occur in cells cultured in elevated glucose or fatty acids. However, the individual roles of glucose, reactive oxygen species, and fatty acids are varied, suggesting multiple pathway involvement.
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, New York.
authors.forename: Jarett
authors.initials: J
authors.lastname: Michaelson
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, New York.
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Hariharan
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, New York. Electronic address: hayden.huang@columbia.edu.
authors.forename: Hayden
authors.initials: H
authors.lastname: Huang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D058065:Diabetic Cardiomyopathies / Q000378:metabolism*; D005227:Fatty Acids / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005947:Glucose / Q000494:pharmacology*; D006943:Hyperglycemia / Q000378:metabolism; D006949:Hyperlipidemias / Q000378:metabolism; D044085:Microfluidics; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009928:Organ Specificity; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000494:pharmacology
chemical_list: D005227:Fatty Acids; D016760:Proto-Oncogene Proteins c-fos; D017382:Reactive Oxygen Species; D005947:Glucose