title: Hyperglycemia enhances function and differentiation of adult rat cardiac fibroblasts.
abstract: Diabetes is an independent risk factor for cardiovascular disease that can eventually cause cardiomyopathy and heart failure. Cardiac fibroblasts (CF) are the critical mediators of physiological and pathological cardiac remodeling; however, the effects of hyperglycemia on cardiac fibroblast function and differentiation is not well known. Here, we performed a comprehensive investigation on the effects of hyperglycemia on cardiac fibroblasts and show that hyperglycemia enhances cardiac fibroblast function and differentiation. We found that high glucose treatment increased collagen I, III, and VI gene expression in rat adult cardiac fibroblasts. Interestingly, hyperglycemia increased CF migration and proliferation that is augmented by collagen I and III. Surprisingly, we found that short term hyperglycemia transiently inhibited ERK1/2 activation but increased AKT phosphorylation. Finally, high glucose treatment increased spontaneous differentiation of cardiac fibroblasts to myofibroblasts with increasing passage compared with low glucose. Taken together, these findings suggest that hyperglycemia induces cardiac fibrosis by modulating collagen expression, migration, proliferation, and differentiation of cardiac fibroblasts.
authors: a Department of Integrative Medical Sciences, Northeast Ohio Medical University, 4209 State Route 44, P.O. Box 95, Rootstown, OH 44272, USA.
authors: Patricia E
authors: PE
authors: Shamhart
authors: Daniel J
authors: DJ
authors: Luther
authors: Ravi K
authors: RK
authors: Adapala
authors: Jennifer E
authors: JE
authors: Bryant
authors: Kyle A
authors: KA
authors: Petersen
authors: J Gary
authors: JG
authors: Meszaros
authors: Charles K
authors: CK
authors: Thodeti
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005355:Fibrosis; D006943:Hyperglycemia / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
chemical_list: D001786:Blood Glucose; D003094:Collagen
keywords: cardiac fibroblast; collagen; collagène; concentration élevée de glucose; diabetes; diabète; fibroblaste cardiaque; high glucose; migration; myofibroblast; myofibroblastes; proliferation; prolifération