Hyperglycemia alone does not stimulate hyaluronan synthesis or cardiac fibroblast activation in vitro, and a diabetogenic diet promotes pro-fibrotic gene expression without excessive hyaluronan accumulation in vivo.
Does hyperglycemia or a diabetogenic diet induce hyaluronan synthesis and cardiac fibroblast activation in murine models?
Hyperglycemia alone does not directly drive hyaluronan synthesis or cardiac fibroblast activation, suggesting other factors in the diabetic milieu are responsible for fibrotic remodeling in diabetic cardiomyopathy.
Diabetic patients are at a greater risk of heart failure due to diabetic cardiomyopathy and worsened outcome post-myocardial infarction. While the molecular mechanisms remain unclear, fibrosis and chronic inflammation are common characteristics of both conditions. Diabetes mellitus (types I and II) results in excessive hyaluronan (HA) deposition in vivo, and hyperglycemia stimulates HA synthesis for several cell types in vitro. HA-rich extracellular matrix contributes to fibrotic, hyperplastic and inflammatory disease progression. We hypothesized that excessive hyperglycemia-driven HA accumulation may contribute to pathological fibroblast activation and fibrotic remodelling in diabetic patients. Therefore, we analysed the impact of both hyperglycemia and diet-induced obesity and insulin resistance on HA matrix formation and cardiac fibroblast activation. Here we report that cardiac fibroblasts isolated from mice on a diabetogenic diet acquire pro-fibrotic gene expression without a concomitant increase in HA matrix deposition. Additionally, hyperglycemia alone does not stimulate HA synthesis or cardiac fibroblast activation in vitro, suggesting that the direct effect of hyperglycemia on fibroblasts is not the primary driver of fibrotic remodelling in cardiac diabetic maladaptation.
Gorski et al. (Tue,) conducted a other in Hyperglycemia and diet-induced insulin resistance. Hyperglycemia and diabetogenic diet vs. 5.5 mM glucose (in vitro); standard chow (in vivo) was evaluated on Hyaluronan synthesis and cardiac fibroblast activation (Acta2 and Col1a1 expression). Hyperglycemia alone does not stimulate hyaluronan synthesis or cardiac fibroblast activation in vitro, and a diabetogenic diet promotes pro-fibrotic gene expression without excessive hyaluronan accumulation in vivo.