Key result
Proteomic analysis of human HFpEF myocardium revealed differential expression of proteins associated with negative regulation of inflammation, oxidative stress, and impaired mitochondrial respiratory chain complexes, particularly in patients with comorbid diabetes.
Why the study?
Heart failure with preserved ejection fraction remains poorly understood, and experimental models have failed to yield effective clinical therapies, necessitating direct investigation of human myocardial samples.
Direct proteomic profiling of human HFpEF myocardium highlights the critical impact of comorbid diabetes on exacerbating mitochondrial dysfunction and metabolic impairment.
Heart failure with preserved ejection fraction (HFpEF) is a highly prevalent but still poorly understood clinical entity. Its current pathophysiological understanding supports a critical role of comorbidities and their chronic effect on cardiac function and structure. Importantly, despite the replication of some HFpEF phenotypic features, to this day, experimental models have failed to bring new effective therapies to the clinical setting. Thus, the direct investigation of HFpEF human myocardial samples may unveil key, and possibly human-specific, pathophysiological mechanisms. This study employed quantitative proteomic analysis by advanced mass spectrometry (SWATH-MS) to investigate signaling pathways and pathophysiological mechanisms in HFpEF. Protein-expression profiles were analyzed in human left ventricular myocardial samples of HFpEF patients and compared with a mixed control group. Functional analysis revealed several proteins that correlate with HFpEF, including those associated with mitochondrial dysfunction, oxidative stress, and inflammation. Despite the known disease heterogeneity, proteomic profiles could indicate a reduced mitochondrial oxidative phosphorylation and fatty-acid oxidation capacity in HFpEF patients with diabetes. The proteomic characterization described in this work provides new insights. Furthermore, it fosters further questions related to HFpEF cellular pathophysiology, paving the way for additional studies focused on developing novel therapies and diagnosis strategies for HFpEF patients.
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Sebastião et al. (2022) studied Heart failure with preserved ejection fraction (HFpEF) (n=27). Heart failure with preserved ejection fraction (HFpEF) vs. Mixed control group without HFpEF was evaluated on Differentially expressed proteins in human left ventricular myocardium. Proteomic analysis of human HFpEF myocardium revealed differential expression of proteins associated with negative regulation of inflammation, oxidative stress, and impaired mitochondrial respiratory chain complexes, particularly in patients with comorbid diabetes.
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