Insight into the Pro-inflammatory and Profibrotic Role of Macrophage in Heart Failure With Preserved Ejection Fraction

The prevalence of heart failure (HF) with preserved ejection fraction (HFpEF) is higher than that of HF with reduced/midrange ejection fraction (HFrEF/HFmrEF). However, no evidence-based guidelines for managing HFpEF have been generated. The current body of knowledge indicates that fibrosis and inflammation are important components of the cardiac remodeling process in HFpEF. In addition, macrophages potentially play an important role in pro-inflammatory and profibrotic processes in HFpEF patients, whereas HFpEF comorbidities could be a driving force for systemic microvascular inflammation and endothelial dysfunction. Under such circumstances, macrophages reportedly contribute to inflammation and fibrosis through 3 phases namely, inflammation, repair, and resolution. Signal transduction pathway-targeted therapies using animal experiments have generated important discoveries and breakthroughs for understanding the underlying mechanisms of HFpEF. However, only a handful of studies have reported promising results using human trials. Further investigations are therefore needed to elucidate the exact mechanisms underlying HFpEF and immune-pathogenesis of cardiac fibrosis.